Classification of the herbicides according to the chemical affinity.
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"605",leadTitle:null,fullTitle:"Earthquake Research and Analysis - Seismology, Seismotectonic and Earthquake Geology",title:"Earthquake Research and Analysis",subtitle:"Seismology, Seismotectonic and Earthquake Geology",reviewType:"peer-reviewed",abstract:"This book is devoted to different aspects of earthquake research. 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The rise of Taylorism, standardisation, electrical systems, electronic systems and computing, and now, quantum computing, has given scheduling a whole World of importance.
\r\n\tFrom practice to a mathematical and technological application, scheduling has become another form of art: an algorithmic art, declined in as many OS and hardware constraints, from embedded systems onboard an aircraft or a spacecraft to databases in all financial and Internet servers.
\r\n\tThey have become ubiquitous so that a large part of our civilisational development is supported by their reliability, redundancy, and optimisation capacity. Like all of our civilisational assets, they are benefiting from scientific breakthrough in computational sciences such as evolutionary algorithms, Artificial Intelligence, and quantum computing. If not by using it, by being in need of adapting to the next generation of computing. Space development is also bringing new challenges, especially in redundancy and reliability.
During the last decades, the scientific community, including government and non-government organizations have increased their interest in detecting and controlling the environmental agents responsible for damages to the human health and sustainability of the ecosystems. This interest has been intensified by the frightening increase on the reports of the anthropogenic action on the environment responsible for damages to the ozone layer, accidental release of wastes and radioactive gases, as well as contamination by pesticides used in agriculture. However, the growth of the human population and of the activities associated with agriculture, industrialization and urbanization have contributed to the depredation of the biodiversity and genetic variability, resulting in the compromise of several species, including man [9].
After the industrial revolution, a great number of chemical substances have been released into the terrestrial and aquatic environments and in the atmosphere. These substances can be transported and transformed by different processes, whose transformation by-products can cause adverse effects on man, as well as damages to the terrestrial and aquatic ecosystems. Several studies have shown the presence of residues of several chemical substances in the air, water, soil, food and organisms in general [10].
Environmental pollution by genotoxic and mutagenic products affects the exposed organism and its future generations, this fact is observed both for animals, and in this case man is included, and for the other groups of organisms such as plants and microorganisms. In order to evaluate the consequences of the anthropogenic activities on the ecosystem it is necessary that the scientific community pays a special attention in the search for understanding the modes of action of xenobiotics present in the ecosystem in the biota exposed. For this, extensive, detailed and ordered studies of the contaminants must be developed with the purpose of preventing the biological impairment, such as inductions of alterations in the genetic materials of the organisms [11].
Some studies have been performed in the attempt to evaluate the behaviour, transformations and effects of chemical agents, both in the environment and in the organisms. Toxicology establishes the limits of concentration or quantity of chemical substances acceptable in the environment by studies on the toxic effects of these substances in the organism and ecosystems [12].
Considering that the use of agrochemicals, such as herbicides, have caused a great environmental contamination, due to their widespread use, it has become indispensable to perform the assessment of the toxicity of these compounds.
Living beings are exposed to the action of numerous agents that are potentially toxic. These agents can be physical, chemical or biological and can provoke in the organisms physiological, biochemical, pathological effects and, in some cases, genetic effects [13]. A great variety of chemical substances with mutagenic potential, both natural and synthetic, have been investigated. Many of these substances are found in food, pharmaceutical drugs, pesticides and in complexes of domestic and industrial effluents. It is known that these compounds can cause detrimental inheritable changes in the genetic material, without these changes being expressed immediately [14]. Thus, several compounds dispersed in the environment can represent danger to human health, since they present a potential to induce mutations [15].
The production of food can occur both by agricultural activities and by livestock. The yield of food production is directly related with the relationship established between the species of interest for production and the other plant, animal, microbial and parasitic biological systems that compete for resources available in the environment [16]. Among the species that jeopardize the agricultural production there are the weeds that, when invade crops, can cause significant loss in the yield and quality of the harvest [17]. Therefore, in order to enhance the productivity and the quality of crops, the removal of weeds from agriculture becomes important.
Before the introduction of selective herbicides as an agricultural practice, the removal of weeds was accomplished manually in an extremely laborious form. Thus, the farmers sought other forms to control weeds, such as, integrating other weed control practices such as crop rotation, tillage and fallow systems [17].
The introduction of selective herbicides in the late 40’s and the constant production of new herbicides in the following decades gave farmers a new tool in the control of weeds [17]. Therefore, the process of modernization of agriculture introduced, in the 60’s, the use of new biological varieties considered more productive, but dependent on chemical fertilizers and intensive use of pesticides, in order to increase productivity. The use of these chemical agents resulted in the increase of productivity, but, on the other hand, brought adverse consequences, since many are harmful substances for man and the environment. The world practice of using agrochemicals for long periods, often indiscriminate and abusive, has raised concerns among the public authorities and experts of public health and sustainability of natural resources [16].
Many agrochemicals are very toxic substances whose absorption in man are almost exclusively oral and can also occur by inhalation or dermally. As a consequence of the human exposure to pesticides, a series of disturbances can be observed, such as gastric, neurological and muscular [18].
Among the pesticides, the main agents of intoxication are the herbicides and insecticides. According to Vasilescu and Medvedovici [19], herbicides are defined as any substance, individually or in mixtures, whose function is to control, destroy, repel or mitigate the growth of weeds in a crop.
The use of herbicides, despite the fact that they are characterized as a highly effective tool in the control of weeds, has led to a change in the phytosociological composition of weeds and to a selection of biotypes resistant to herbicides, besides also causing impacts in the environment and human health. According to He et al. [20], herbicides are the most used chemical substances throughout the world. During the 90’s, the global pesticide sales remained relatively constant, between 270 and 300 billions of US dollars, and 47% of this value corresponded to herbicides and 79% to insecticides. Since 2007, herbicides assumed the first place among the three major categories of pesticides (insecticides, fungicides/bactericides, herbicides) [21].
The use of herbicides to control weeds has been a common practice in global agriculture, mainly with the objective to increase agricultural production. However, when these chemicals are used in an uncontrolled manner, they can cause impacts on non-target organisms, especially on those that live in aquatic environments [22].
According to Chevreuil et al. [23], Kim and Feagley [24] and Abdel-Ramham et al. [25], most of the toxic effects of the herbicides on animals and plants were insufficiently investigated. As a consequence of the lack of information about the action of herbicides in the biological environment, these chemical agents can also represent a problem to human health [26, 27]. The impact of a pesticide in the environment depends on its dispersion mode and its concentration, as well as its own toxicity [28]. The mutagenic effects of the herbicides can result from several reactions with the organism, as a direct action of the compound on the nuclear DNA; incorporation in the DNA during cell replication; interference in the activity of the mitotic or meiotic division, resulting in incorrect division of the cell [29].
Some herbicides interfere directly in the cell division of plants, elongation and/or cell differentiation, causing disturbances in the functioning of the roots or vascular tissues [30]. In animals, herbicides can act in several tissues or organs and, sometimes, are associated with tumorigenic processes [31].
Jurado et al. [32] listed the general advantages and disadvantages of using herbicides. In this list, the authors cited as advantages: kill unwanted plants; help crops grow since it eliminates weeds that compete with crops for water, nutrients and sunlight; can be safely used in plantations, while the manual or mechanical removal processes of weeds can cause damages to crops; can be used in geographically close crops; in most cases, only one application of the herbicide is sufficient to control the weeds, while the other methods must be constantly used; are easy to use; have fast action; are relatively inexpensive and are economically more viable than manual removal; non-selective herbicides can be used to eliminate vegetation cover in areas intended for the construction of residences and/or roads; to eradicate plants bearing diseases; and since some herbicides are biodegradable, they can become relatively inert after some time. The disadvantages listed by the authors are: some herbicides are not biodegradable and, thus, can persist in the environment for a long period of time; all herbicides are, at least, mildly toxic; can cause diseases and even accidental death (case of paraquat); can be carried into rivers by rainwater or be leached to groundwater polluting these environments; some herbicides can accumulate in the food chain and are toxic for animals, including man.
According to Moreland [33], herbicides are designated by common names approved by the Weed Science Society of America (WSSA) or by the British Standards Institution. Organic herbicides are classified according to their application method, chemical affinity, structural similarity, and by their mode of action [34]. In relation to the application methods, herbicides can be classified into two groups: soil application and foliar application. According to Jurado et al. [32], all the herbicides applied in the pre-planting (surface or incorporation) and pre-emergence (in crops, weeds or both) are classified as herbicides of soil application and those applied in the post-emergence are classified as foliar application.
Moreover, herbicides can be classified according to their mode of action. Following, it will be presented the classes of herbicides, according to their mode of action, based in the classification of Moreland [33] :
electron transport inhibitors: electron transport is inhibited when one or more intermediary electron carriers are removed or inactivated or even when there is interference in the phosphorylation. Example: diuron, atrazine.
uncouplers: uncouplers dissociate the electron transport of the ATP formation through the dissipation of the energetic state of the thylakoid membrane, before the energy can be used to perform the high endergonic reaction of ADP phosphorylation. Example: perfluidone.
energy transference inhibitors: inhibition of energy transference inhibitors acts directly in the phosphorylation, as well as inhibitors of the electron transport, which inhibit both the electron flow and the formation of ATP in coupled systems. Example: 1,2,3-thiadiazol-phenylurea, nitrofen.
inhibitory uncouplers: the term “inhibitory uncouplers” was used by Moreland [33] to indicate that the herbicides interfere in reactions affected by electron transport inhibitors and by uncouplers; These “inhibitory uncouplers” inhibit the basal transport, uncoupled and coupled of electrons. The herbicides classified in this group affect both the electron transport and the gradient of protons. Examples: acylanilides, dinitrophenols, imidazole, bromofenoxim.
electron acceptors: the compounds classified in this group are able to compete with some component of electron transport and consequently suffer reduction. Examples: diquat, paraquat.
inhibitors of the carotenoid synthesis: this class of herbicides acts to inhibit the synthesis of carotenoids, resulting in accumulation of precursors of carotenoid devoid colour (phytoene and phytofluene). The inhibition of carotenoid synthesis leads to the degradation of chlorophyll in the presence of light; degradation of 70s ribosomes; inhibition of the synthesis of proteins and loss of plastids. Examples: amitrole, dichlormate, SAN6706.
electron transport inhibitors: defined as substances that have the ability to interrupt the electron flow in some point of the respiratory chain, acting in one of the complexes. Examples: diphenylether herbicides.
uncouplers: in appropriate concentrations, the classic uncouplers, that are weak lipophilic acids or bases, prevent the phosphorylation of ADP without interfering in the electron transport. Generally, any compound that promotes the dissipation of the energy generated by the electron transport, except for the production of ATP, can be considered as uncoupler. Example: isopropyl ester glyphosate.
energy transfer inhibitors: compounds of this group inhibit the phosphorylating electron transport, when the apparatus of energy conservation of the mitochondria is intact and the inhibition is circumvented by uncouplers. They combine with an intermediary in the coupling energy chain and, thus, block the phosphorylation sequence that leads to the ATP formation. No herbicide seems to act as an energy transfer inhibitor.
inhibitory uncouplers: most of the herbicides that interfere in the oxidative phosphorylation present a great variety of responses and are classified as uncoupling inhibitors. At low molar concentrations, herbicides fulfil almost all, if not all, of the requirements established for uncouplers, but at high concentrations they act as electron transport inhibitors. Herbicides that present this behaviour are the same classified as uncoupler inhibitors of the photoinduced reactions in the chloroplast. Example: perfluidone.
compositional alterations: can modify or alter the composition of lipids in the membrane and can also act in the metabolism and synthesis of lipids. Examples: dinoben, chlorambem, perfluidone.
effects in the permeability and integrity. Examples: paraquat, diquat, oryfluorfen, oryzalin.
The herbicides can still be classified according to the chemical affinity. Table 1 shows the chemical classes and examples of each class, according to Rao [34].
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
Acetamides | \n\t\t\tAcetochlor, alachlor, butachlor, dimethenamid, metolachlor, napropamide, pronamide, propachlor, propanil | \n\t\t
Aliphatics | \n\t\t\tChlorinated aliphatic acid (TCA), acrolein, dalapon | \n\t\t
Arsenicals | \n\t\t\tDisodium methanearsonate (DSMA), monosodium methanearsonate (MSMA), cacodylic acid | \n\t\t
Benzamides | \n\t\t\tIsoxaben | \n\t\t
Benzoics | \n\t\t\tDicamba | \n\t\t
Benzothiadiazoles | \n\t\t\tBentazon | \n\t\t
Bipyridiliums | \n\t\t\tDiquat, paraquat | \n\t\t
Carbamates | \n\t\t\tAsulam, desmedipham, phenmedipham | \n\t\t
Cineoles | \n\t\t\tCinmethylin | \n\t\t
Cyclohexanediones (cyclohexenones) | \n\t\t\tClethodin, cycloxidim, sethoxydim, tralkoxydim | \n\t\t
Dinitroaniniles | \n\t\t\tBenefin, ethalfluralin, fluchloralin, pendimethalin, prodiamine, trifluralin | \n\t\t
Diphenylethers | \n\t\t\tAcifluorfen, bifenox, fluoroglycofen, fomesafen, lactofen, oxyfluorfen | \n\t\t
Imidazolidinones | \n\t\t\tButhidazole | \n\t\t
Imidazolinones | \n\t\t\tImazapyr, imazaquin, imazethapyr, imazamethabenz | \n\t\t
Imines | \n\t\t\tCGA-248757 | \n\t\t
Isoxazolidinones | \n\t\t\tClomazone | \n\t\t
Nitriles | \n\t\t\tBromoxynil, dichlobenil, ioxynil | \n\t\t
Oxadiazoles | \n\t\t\tOxadiazon | \n\t\t
Oxadiazolidines | \n\t\t\tMethazole | \n\t\t
Phenols | \n\t\t\tDinoseb | \n\t\t
Phenoxyalkanoic acids Phenoxyacetics Phenoxybutyrics Arylophenoxy propionics | \n\t\t\t2,4-D, MCPA, 2,4,5-T 2,4-DB Dichlorprop, diclofop, fenoxaprop, fluazifop-P, quizalofop-P | \n\t\t
\n\t\t\t\t | \n\t\t\tFlumiclorac | \n\t\t
Phenylpyridazines | \n\t\t\tPyridate | \n\t\t
Phenyl Triazinones (Aryl Triazinones) | \n\t\t\tSulfentrazone | \n\t\t
Phthalamates | \n\t\t\tNaptalam | \n\t\t
Pyrazoliums | \n\t\t\tDifenzoquat | \n\t\t
Pyridazinones | \n\t\t\tNorflurazon, pyrazon | \n\t\t
Pyridinecarboxylic Acids | \n\t\t\tClopyralid, picloram, triclopyr | \n\t\t
Pyridines | \n\t\t\tDithiopyr, thiazopyr | \n\t\t
Pyridinones | \n\t\t\tFluridone | \n\t\t
Pyrimidinythio-benzoates (Benzoates) | \n\t\t\tPyrithiobac | \n\t\t
Quinolinecaryoxylic acids | \n\t\t\tQuinclorac | \n\t\t
Sulfonylureas | \n\t\t\tBensulfuron, chlorimuron, chlorsulfuron, halosulfuron, metsulfuron, nicosulfuron, primisulfuron, prosulfuron, sulfometuron, thifensulfuron, triasulfuron, tribenuron | \n\t\t
Tetrahydropyrimidinones | \n\t\t\tYet to be commercialized | \n\t\t
Thiocarbamates | \n\t\t\tButylate, diallate, EPTC, molinate, pebulate, thiobencarb, triallate | \n\t\t
Triazines | \n\t\t\tAmetryn, atrazine, cyanazine, hexazinone, prometryn, simazine | \n\t\t
Triazinones | \n\t\t\tMetribuzin | \n\t\t
Triazoles | \n\t\t\tAmitrole | \n\t\t
Triazolopyrimidine Sulfonanilides | \n\t\t\tFlumetsulam | \n\t\t
Uracils | \n\t\t\tBromacil, terbacil, UCC-C4243 | \n\t\t
Ureas | \n\t\t\tDiuron, fluometuron, linuron, tebuthiuron, | \n\t\t
Unclassified herbicides | \n\t\t\tBensulide, ethofumesate, fosamine, glufosinate, glyphosate, tridiphane | \n\t\t
Classification of the herbicides according to the chemical affinity.
When a herbicide is used to control weeds, sometimes a majority of the compound ends up in the environment, whether it is in the soil, water, atmosphere or in the products harvested [17]. Due to the widespread use of these chemicals over the years, there has been an accumulation of these residues in the environment, which is causing alarming contaminations in the ecosystems [35] and negative damages to the biota. To Bolognesi and Merlo [3], the widespread use of herbicides has drawn the attention of researchers concerned with the risks that they can promote on the environment and human health, since they are chemicals considered contaminants commonly present in hydric resources and soils. According to the same authors, herbicides represent a high toxicity to target species but it can be also toxic, at different levels, to non-target species, such as human beings. Herbicides can cause deleterious effects on organisms and human health, both by their direct and indirect action [2]. Among the biological effects of these chemicals, it can be cited genetic damages, diverse physiological alterations and even death of the organisms exposed. Some herbicides, when at low concentrations, cannot cause immediate detectable effects in the organisms, but, in long term can reduce their lifespan longevity [4]. Herbicides can affect the organisms in different ways. As with other pesticides, the accumulation rate of these chemicals on biota depends on the type of the associated food chain, besides the physicochemical characteristics (chemical stability, solubility, photo-decomposition, sorption in the soil) of the herbicide [5-6]. Thus, despite the existence of several toxicological studies carried out with herbicides, in different organisms, to quantify the impacts of these pollutants and know their mechanisms of action [7, 8, 2], there is a great need to expand even more the knowledge about the effects of different herbicides in aquatic and terrestrial ecosystems. Data obtained from
According to Jurado et al. [32], when herbicides are applied in agricultural areas they can have different destinations, since being degraded by microorganisms or by non- biological means or even be transported by water, to areas distant from the application site. Thus, according to the same authors, the organisms can be then exposed to a great number of these xenobiotics as well as their metabolites.
The fate of the compound in the soil depends on the characteristics of the compound and the soil. The hydrogenionic properties of a compound in the soil determines its sorption characteristics, such as, acid herbicides in soils with normal pH are negatively charged and consequently are movable in most of the soils [17]. Some groups of pesticides are neutral in soils with normal pH but due to electronic dislocations in the molecules, they can bind to soil colloids by several forms [36].
According to Kudsk and Streiberg [17], during the last two decades, several studies have been completed to predict the behaviour of pesticides in the soil. Despite the numerous efforts to assess the effects of herbicides in the soil, there are conflicting data in the literature on the subject, where some studies show that the residues of pesticides can be sources of carbon and energy to microorganisms, and then are degraded and assimilated by them, while other reports affirm that pesticides produce deleterious effects to the organisms and biochemical and enzymatic processes in the soil [37]. According to Hussain et al. [37], in general, the application of pesticides, and here it is also included herbicides, made long term, can cause a disturbance in the biochemical balance of the soil, which can reduce its fertility and productivity.
Once in the soil, herbicides can suffer alteration in their structure and composition, due to the action of physical, chemical and biological processes. This action on the herbicides is the one that will determine their activity and persistence in the soil. Some molecules, when incorporated into the soil, are reduced by volatilization and photo-decomposition. Once in the soil, herbicides can suffer the action of microorganisms, which, added to the high humidity and high temperature, can have their decomposition favoured [38]. If they are not absorbed by plants, they can become strongly adsorbed on the organic matter present in the colloidal fraction of the soil, be carried by rainwater and/or irrigation and even be leachate, thus reaching surface or groundwater [39].
The prediction of the availability of herbicides to plants has two purposes: 1. ensure that the herbicide reaches the roots in concentrations high enough to control weeds, without compromising the agricultural productivity; 2. predict if the compound is mobile in the soil to estimate how much of the herbicide can be leachate from the roots zone to groundwater [17].
The contamination of aquatic environments by herbicides has been characterized as a major world concern. This aquatic contamination is due to the use of these products in the control of aquatic plants, leachate and runoff of agricultural areas [40]. According to He et al. [20], it is a growing public concern about the amount of herbicides that have been introduced into the environment by leachate and runoff, not to mention that the contaminations of the aquatic environments generally occur by a mixture of these compounds and not by isolated substances.
Guzzella et al. [1] did a survey on the presence of herbicides in groundwater in a highly cultivated region of northern Italy. The researchers monitored for two years the presence of 5 active ingredients and 17 metabolites resulting from these compounds. The authors verified that atrazine, although banned in Italy since 1986, was the major contaminant of the groundwater of the sites studied, they also observed that the concentration of at least one of the compounds studied exceeded the maximum allowed concentration in 59% of the samples likely due in both cases to off-label herbicide use. This scenario could be, in long term, a serious problem for the quality of this water, which is used as drinking water.
Toccalino et al. [41] carried out a study to verify the potential of chemical mixtures existing in samples of groundwater used for public supply. In these samples, the most common organic contaminants were herbicides, disinfection by-products and solvents. The authors concluded that the combined concentrations of the contaminants can be a potential concern for more than half of the samples studied and that, even though the water destined to public supply pass through treatments to reduce contaminations and meet the legislations, it can still contain mixtures at worrying concentrations.
Saka [42] evaluated the toxicity of three herbicides (simetryn, mefenacet and thiobencarb) commonly used in rice planting in Japan, on the test organism
In a study conducted by Ventura et al. [8], it was observed that the herbicide atrazine has a genotoxic and mutagenic effect on the species
Bouilly et al. [44] studied the impact of the herbicide diuron on
In general, when herbicides contaminate the aquatic ecosystem, they can cause deleterious effects on the organisms of this system. Thus, organisms that live in regions impacted by these substances, whose breeding period coincides with the application period of the herbicides, can suffer serious risks of development and survival of their offspring.
Hladik et al. [45] evaluated the presence of two herbicides (chloroacetamide and triazine), as well as their by-products, in drinking water samples of the Midwest region of the United States. The authors detected the presence of neutral chloroacetamide degradates in median concentrations (1 to 50 ng/L) of the water samples. Furthermore, they found that neither the original chloroacetamide herbicides nor their degradation products were efficiently removed by conventional water treatment processes (coagulation/flocculation, filtration, chlorination). According to Bannink [46], about 40% of the drinking water from Netherlands is derived from surface water. The Dutch water companies are facing problems with the water quality due to contamination by herbicides used to eliminate ruderal plants. These data serve as alerts for the presence of herbicides and their degradation products in drinking water, pointing out the need for the development of new treatment systems that could be more efficient to eliminate this class of contaminants.
According to Ying and Williams [40], organic herbicides, when in aquatic ecosystems, can be distributed in several compartments depending on their solubility in water. These compartments include water, aquatic organisms, suspended sediment and bottom sediment. The more hydrophilic the organic pesticide, the more it is transported to the aqueous phase, and the more hydrophobic a pesticide is, the more it will be associated to the organic carbon of the suspended and bottom sediment [47]. The sorption of the herbicides in sediments in suspension can reduce the degradation rate of the herbicides in water, and the movement of the sediment in suspension can transport the pesticides from one place to another, entering into the tissue of organisms or settling on the bottom [40].
A study conducted by Jacomini et al. [48] evaluated the contamination of three matrices (water, sediment and bivalve molluscs) collected in rivers influenced by crops of sugar cane in São Paulo State-Brazil. In this study, the authors observed that the highest concentrations of residues of the herbicide ametrin were present in the sediment, showing the persistence of this compound in the sediments of rivers and its potential to mobilize between the compartments of the aquatic system, such as water and biota.
When the herbicides are dispersed in the water or sediments in suspension of the rivers, they can end up in other ecosystems such as estuaries. Duke et al. [49], when studying the effect of herbicides on mangroves of the Mackay region, found out that diuron, and even other herbicides, are potentially responsible for the mangrove dieback. According to the authors, the consequences for this death would be the impoverishment of the quality of the coastal water with an increase of the turbidity, nutrients and sediment deposition, problems in the fixation of seedlings and consequent erosion of the estuaries.
In a review conducted by Jones [50], the author highlights the contamination of marine environments by herbicides (such as diuron), discussing that the contamination of these environments can occur by transport of these substances of agricultural or non cultivated areas (roadsides, sports fields, train tracks), runoff by storms and tailwater irrigation release), pulverizations and accidental spills. These contaminations mean that the photochemical efficiency of intracellular symbiotic algae of the coral, in long term, may be compromised, leading to a loss in the symbiotic relationship of the coral with the algae and a consequent bleaching of corals. Still considering the marine ecosystem, Lewis et al. [51] verified that the runoff of pesticides from agricultural areas influence the health of the Great Barrier Reef in Australia and can disturb this sensitive ecosystem.
Considering the prior literature, it is likely possible that the effects of herbicides do not occur only at the places that they are applied but also in places distant from their application. Moreover, herbicides can induce alterations in non-target organisms, altering the survival and the equilibrium of the ecosystems, whether they are aquatic or terrestrial. Thus, much care must be taken when introducing these substances into the environment and more studies should be conducted in order to thoroughly understand the environmental consequences that herbicides can cause.
Many studies have evaluated the impact of different chemical classes of herbicides using different doses, organisms and bioassays, focusing on toxic, cytotoxic, genotoxic, mutagenic, embryotoxic, teratogenic, carcinogenic and estrogenic effects.
With respect to the toxicity, some herbicides pose major concerns when applied in regions close to water resources due to their highly toxic potential to many aquatic organisms [52].
Biological tests of toxicity and mutagenicity are, according to Moraes [53], indispensable for the evaluation of the reactions of living organisms to environmental pollution and also for the identification of the potential synergistic effects of several pollutants. The impact that toxic materials can promote in the integrity and function of DNA of several organisms has been investigated [54]. Several biomarkers have been used as tools for the detection of the toxic, genotoxic and mutagenic effects of pollution. Among them we can cite the presence of DNA adducts, chromosome aberrations, breaks in the DNA strands, micronuclei formation and other nuclear abnormalities, besides induction of cell death [55].
Most of the tests used to detect the mutagenic potential of chemical substances are based on the investigation of possible inductions of chromosome damages such as structural alterations, formation of micronuclei, sister chromatid exchanges, assessment of mutant genes or damages in the DNA, using different test organisms, such as bacteria, plants and animals, both
According to Veiga [57], it is possible to estimate the genotoxic, mutagenic, carcinogenic and teratogenic effects of agrochemicals by relatively simple methods. Several studies have been carried out by several researchers concerned with the harmful effects of pesticides in an attempt to verify their possible physiological [58, 59], mutagenic [7, 8, 60, 61, 62] and carcinogenic effects [63].
The interaction between different methods of evaluating the toxic, genotoxic and mutagenic potential provides a more global and comprehensive view of the effect of a chemical agent. For the monitoring of organisms exposed to chemical agents, the chromosome aberration test, micronucleus test and comet assay have been widely used [64]. A few studies also have shown the toxic effects of chemicals, by cell death processes, both necrotic and apoptotic [65].
According to Kristen [66], the dramatic expansion in the production of xenobiotic compounds by anthropogenic activities has compromised the environment by the introduction of millions of chemicals with toxic potential to biological systems.
Cytogenetic tests are adequate to identify the harmful effects of substances, in their several concentrations and different periods of exposure. These tests, generally performed with test organisms, are commonly applied in biomonitoring to the extent of pollution and in the evaluation of the combined effects of toxic and mutagenic substances on the organisms in the natural environment [53]. Micronuclei assays are efficient to assess the mutagenic activity of herbicides both in laboratorial and field assays [67]. The comet assay can be used to evaluate damages in proliferating cells or not, in
The toxic, cytotoxic, genotoxic, mutagenic, embryotoxic, teratogenic carcinogenic and estrogenic effects caused by herbicides on various organisms could be exemplified by studies as described below.
Atrazine is a triazinic herbicide, classified as moderately toxic of pre- and post-emergence, used for the control of weeds in crops of asparagus, corn, sorghum, sugarcane and pineapple [70]. According to Eldridge et al. [71], triazinic herbicides are among the most used pesticides in agriculture due to their ability to inhibit the photosynthesis of weeds in crops [16].
Triazine herbicides are extensively used in the United States to control grass, sedge and broadleaf weedsduring the cultivation of maize, wheat, sorghum, sugarcane and conifers [72]. In Brazil, these herbicides are widely used on crops of sugarcane and maize. Due to the widespread use of triazine herbicides in the agriculture and, therefore, its high exposure potential for humans, the United States Environmental Protection Agency (USEPA) has conducted a special review on the published and non published data of several triazine herbicides [73]. According to Nwani et al. [22], the herbicide atrazine is widely used in crops worldwide. The dangers, both toxic and genotoxic of this herbicide have been revised; however, there is an urgent need for more detailed studies on the mode of action of this compound. Atrazine has been tested in several systems, but there are shortcomings in relation to certain tests performed and some evidences of the genotoxic effects,
Several studies using the test system
Sorghum plants treated with atrazine presented an increase in the number of their chromosomes, multinucleated cells, aneuploidy and polyploidy, and abnormalities in the mother cells of the pollen grain, which suggests that this herbicide interferes in the stability and also in the meiosis [80].
Popa et al. [70] observed that atrazine, when applied in high concentrations in maize seedlings, can induce chromosome breaks, visualized by the presence of single and paired chromosome fragments; a high frequency of chromatids and chromosome bridges; lagging chromosomes and presence of heteropolyploid or polyploid cells. Grant and Owens [81] showed that atrazine induced chromosome breaks (in mitosis and meiosis) in the species
Hayes et al. [82] investigated the effect of the herbicide atrazine on wild leopard frogs (
According to Gammon et al. [83], some publications have reported a possible feminization of frogs, both in laboratorial assays and field studies. This effect is mainly due to the action of the enzyme aromatase; however, published research not shown the measures of this enzyme. Thus, there are doubts about the feminization theory, except for the studies that presented a great number of frogs with morphological alterations related to very high levels of atrazine.
Nwani et al. [22] evaluated the genotoxic and mutagenic effects of the herbicide Rasayanzine, whose active ingredient is atrazine, using the comet assay and micronucleus test, in erythrocytes and gill cells of the fish
A study carried out by Çavas [84] compared the genotoxic effects of the active ingredient atrazine and its commercial formulation Gesaprim, in the concentrations of 5, 10 and 15 µg/L, by the comet assay and micronucleus test, in erythrocytes of the fish gibel carp (
Atrazine has also been tested to evaluate the ability to induce cytogenetic damages in rodents. Meisner et al. [85] submitted rats to 20 ppm of atrazine (by water ingestion) and did not observe, after exposure to the herbicide, an increase in the number of chromosome aberrations. In a similar study, Roloff et al. [86] reported that there was no significant increase of chromosome aberrations in cells of rat bone marrow, when they were fed with 20 ppm of atrazine.
Wu et al. [87] assessed the embryotoxic and teratogenic effects of atrazine, at the doses of 25, 100 and 200 mg/Kg/day, in Sprague-Dawley rats. Prenatal exposure to the highest dose of the herbicide tested caused hypospadias in 10.23% of male newborn rats, and the lowest dose induced diverse embryotoxic damages in some individuals. According to Modic et al. [88], high doses of atrazine (50 or 200 mg/kg/day), administered daily in male Wistar rats at 60 days of age, promoted alterations in the levels of several hormones in the serum of these individuals, observed by slight increases in the levels of androstenedione testosterone, estradiol, estrone, progesterone and corticosterone, quantified by radioimmunoassay.
To obtain more concise data on the genotoxicity of triazine herbicides, Tennant et al. [89] used the comet assay methodology, which showed to be highly sensitive for the detection of low rates of damages in the DNA. According to these authors, the comet assay showed that atrazine induced a small increase in the damages in the DNA in leukocytes of rats. Moreover, by the comet assay, Clements et al. [90] reported that atrazine induced a significant increase in the frequencies of damages in the DNA of erythrocytes of bullfrog tadpoles, noting the genotoxic potential of this herbicide for this species of amphibian, from the concentration of 4.8 mg/L.
Studies about the cytotoxicity, genotoxicity and mutagenicity of the atrazine herbicide (oral gavage - dose 400 mg/kg/day), carried out by Campos-Pereira et al. [91], have shown the induction of lipid peroxidation and liver damage, death of hepatocytes, and micronucleus formation in exposed Wistar rats. Tests performed by Ventura et al. [8] showed that the same triazine pesticide was able to induce significant DNA fragmentation when using the comet assay, and nuclear alterations and micronuclei using the micronucleus test in
Ruiz and Marzin [92] assessed the genotoxic and mutagenic effects of the herbicide atrazine by two
The genotoxicity of herbicides, such as atrazine, has also been evaluated by the comet assay by the use of human blood lymphocytes. According to Ribas et al. [69], blood cells treated with the herbicide atrazine, at concentrations of 50-200 µg/l, showed an extensive migration of DNA, mainly at concentrations of 100 and 200 µg/l.
In mammalian test systems, submitted to the action of the herbicide atrazine, most of the results seem to be negative, except for the results of Loprieno and Adler [95], who obtained a significant increase in the frequency of chromosome aberrations in bone marrow cells of rats, and the data obtained by Meisner et al. [94], who described an induction of chromosome aberrations in cultured human lymphocytes. While the results from bacteria and mammal test systems are almost all negative, atrazine exhibits clear mutagenic effects in different plant test systems, by inducing chromosome aberrations in
Studies performed by Zeljezic et al. [101] had already reported that atrazine does not present genotoxicity or capacity to induce apoptosis or necrosis in human lymphocytes, while the treatment of these cells with the commercial formulation, Gesaprim, significantly increased the rates of damages in DNA, observed by the comet assay. Srivastava and Mishra [102] observed results that are in agreement with the findings of Zeljezic et al. [101] and Çavas [84], in which the exposure to different concentrations of Gesaprim inhibited the mitotic index and increased the frequencies of micronuclei and chromosome aberrations in somatic cells of
Toxic effects of atrazine, alone or associated with the herbicide butachlor, for the freshwater species such as the green alga
Simazine and cyanazine, as well as atrazine, are widely used as triazine herbicides of pre- and post-emergence weed control, whose residues have been carried to the source of drinking water of several agricultural communities. These compounds also present a potential risk to humans, mainly due to their presence in food [103]. Studies on the effect of atrazine, simazine and cyanazine performed by Kligerman et al. [104], found that there was not a significant increase in the sister chromatid exchanges and chromosome aberrations in cultured human lymphocytes exposed to these herbicides, up to the solubility limit in aqueous solution using 0.5% of dimethyl sulfoxide. However, Adler [105] observed that doses of 1500 and 2000 mg/Kg of atrazine, administered by oral gavage in rats, induced dominant lethal mutations and chromatin breaks in the bone marrow of these organisms.
Kligerman et al. [103] observed that the association of the herbicides atrazine, simazine and cyanazine did not induce micronuclei in polychromatic erythrocytes of bone marrow of female rats (C57B1/6) exposed by intraperitoneal injection, even when very high doses of these herbicides were administered (125, 250 and 500 mg/Kg of atrazine; 500, 1000 and 2000 mg/Kg of simazine; 100, 200 and 400 mg/kg of cyanazine), showing an absence of genotoxic potential of these compounds for the organism tested.
On the other hand, Hrelia et al. [106] showed that males and females of Sprague-Dawley rats exposed by oral gavage to doses of 56, 112 and 224 mg/kg of cyanazine, did not present significant increases in chromosome aberrations.
Taets et al. [107] evaluated the clastogenic potential of environmental concentrations of the triazine herbicides simazine (0.001 to 0.004 µg/mL), cyanazine (0.003 to 0.012 µg/mL) and atrazine (0.003 to 0.018 µg/mL), in Chinese Hamster Ovary (CHO) cells, using flow cytometry assay. The authors proved the clastogenic action for the herbicides atrazine and cyanazine, proven by the high indices of damages in the cells exposed to atrazine and by the significant frequencies of damages observed in the cells exposed to cyanazine.
The herbicide terbutryn is an s-triazine herbicide used pre- and post-emergence and widely used worldwide as an agent to control grass, sedge, and broadleaf weeds in vegetables, cereals and fruit trees. It is an herbicide persistent in the environment, which tends to dislocate by the flow of water and leachate [108].
An
The 2,4-D (2,4-dichlorophenoxyacetic acid) is an herbicide from the group of the polychlorinated aromatic hydrocarbons that has been widely used throughout the world [109] since 1944, to control broadleaf weeds and woody plants [110]. Its action mimics the auxin of plants [111]. According to Martínez-Tabche et al. [112], this herbicide mimics the action of the hormone indole acetic acid, when used in small quantities but it is highly cytotoxic in high concentrations.
According to Ateeq et al. [113], the increase in the frequency of micronuclei and altered cells was significant, when erythrocytes of catfish (
Studies carried out by Suwalsky et al. [114] in nerve cells of
According to Gómez et al. [115], the main and most common entrance route of 2,4-D in fish is through gills. This herbicide can cause several adverse symptoms to these organisms, such as bleeding, increased damage to the kidneys and renal functions, as well as hepatic degeneration.
Martínez-Tabche et al. [112] evaluated the toxicity of different concentrations of the herbicides 2,4-D and paraquat (0, 5, 75 and 150 mg/L), using several assays (acute lethality test, lipid peroxidation assay by quantification of MDA – Malondialdehyde – and comet assay) in rainbow trout (
González et al. [116] proved the genotoxicity of 2,4-D due to a significant increase of SCE in CHO cells treated with the concentrations of 2 to 4 ug/mL of this herbicide. Madrigal-Bujaidar et al. [117] also showed the genotoxic potential of 2,4-D, due to a clastogenc effect of this herbicide at the doses of 100 and 200 mg/Kg, detected by a significant increase of SCE in bone marrow cells and germ cells of rats. Soloneski et al. [118] studied the genotoxic effects of different concentrations (0, 10, 25, 50 and 100 mg/mL) of the herbicide 2,4-D (2,4-dichlorophenoxyacetic) and its commercial derivative 2,4-D DMA (Dimethylamine 2,4-D salt), by the SCE assay and analyses of cell cycle progression and mitotic index human lymphocytes maintained in culture, in the presence (human whole blood - WBC) and absence (plasma leukocyte cultures - PLC) of erythrocytes. These compounds did not induce significant frequencies of SCE and only the concentration of 100 mg/mL of 2,4-D caused alterations in the progression of the cell cycle in PLC, while the different concentrations of 2,4-D and 2,4-D DMA induced a significant increase in the frequency of SCE and a significant delay in the cell proliferation rates in WBC. Moreover, both 2,4-D and 2,4-D DMA presented a dose-response inhibition of the mitotic activity in PLC and WBC. Based on these results, the authors concluded that the herbicide and its commercial derivative presented genotoxic potential, which was higher in the presence of human erythrocytes.
Morgan et al. [119] showed, by embryotoxicity and teratogenicity assays carried out with
The estrogenic potential of 4 herbicides (triclopyr; 2,4-D; diquat dibromide and glyphosate), was evaluated by the
Glyphosate is a non-selective organophosphorus, broad spectrum, post-emergence herbicide, widely used in agriculture, mainly to control grasses, sedges, and broadleaf weeds [121]. Its action occurs by the inhibition of the biosynthesis of aromatic amino acids [122]. Its main mode of action is by the inhibition of the enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), which is essential in plants for the synthesis of the referred amino acids. Since this enzyme is absent in animals, this herbicide should be relatively non toxic for these organisms [123]. There are many conflicting data on the toxicity of glyphosate and its commercial formulations.
According to Solomon and Thompson [124], environmental toxicology of glyphosate has been extensively reviewed by a series of international regulatory agencies. According to the authors, as glyphosate binds strongly with organic matter, it is considered immobile in soils and sediments. This binding also removes glyphosate from water, reducing efficiently, the exposure of aquatic organisms. As the acute exposures are most likely to occur, the measures of effect are the most adequate for the purpose of risk assessment. However, in general, the authors affirm that glyphosate presents a low potential of acute toxicity for wild animals, including mammals, birds, fish and aquatic invertebrates.
Williams et al. [125] carried out a critical review on the toxicity of the herbicide RoundUp™ and of its active ingredient glyphosate. The analysis of the toxicity data, carried out by pattern tests and evaluation criteria, indicated that there is no evidence that glyphosate causes direct damages in the DNA, both in assays performed
A study on the impact of the herbicide glyphosate and its commercial formulation Roundup™, in three microorganisms of food interest (
Relyea [128] assessed the toxic potential of environmentally relevant concentrations of glyphosate on three species of tadpoles (wood frog [
Studies on the genotoxic potential of the active ingredient glyphosate, present in the commercial formulation Roundup, were performed on the roots of smooth hawksbeard (
Martini et al. [123] studied the effects of the commercial formulation of glyphosate in the proliferation, survival and differentiation of the 3T3-L1 fibroblasts (a mammal cell line), by the cell viability test with Trypan, MTT test, enzymatic activity assay of caspase-3 and staining assay with annexin-V and propidium iodide. The results showed that glyphosate inhibits the cell proliferation and induces apoptosis in a dose-dependent way, besides decreasing significantly the ability of the fibroblasts to differentiate to adipocytes. These data suggest the occurrence of important cell damages mediated by the action of this herbicide, indicating that glyphosate presents a potential risk factor for human health and the environment.
Dallegrave et al. [130] evaluated the teratogenicity of the herbicide glyphosate, marketed in Brazil as Roundup (36% of glyphosate and 18% of the surfactant polyoxyethyleneamine), to females of Wistar rats. The females treated orally with three different doses of glyphosate (500, 750, 1000 mg/Kg) from the 6th to the 15th day of gestation. After performing caesarean sections on day 21 of gestation, the number of corpora lutea, implantations, live and dead foetuses and reabsorptions, as well as the external malformations and skeletal malformation were recorded and analyzed. It was observed a mortality rate of 50% of the females treated with the highest concentration of glyphosate; the authors verified that there was a dose-response relationship directly proportional to the increase in the number of skeletal alterations found. These results led the authors to conclude that the commercial formulation of glyphosate (Roundup) is toxic for females of Wistar rats and is able to induce a delay in the fetal skeletal development of this species. It is important to consider that the toxicity and teratogenicity observed can result from both the action of glyphosate as well asthe surfactant present in the commercial formulation.
The oral administration of high doses of glyphosate (3500 mg/Kg) in Charles River COBS CD rats, between the 6th to the 19th day of pregnancy, and in rabbits, between the 6th to the 27th day of pregnancy, showed significant indices of maternal mortality for both species, as well as increase in the number of foetuses with reduced ossification of sternebrae [131], proving the toxicity and teratogenicity of this concentration of the herbicide for the organisms tested.
Relyea [132] performed a study to observe the impact of two herbicides (glyphosate and 2,4-D) in the biodiversity of aquatic communities containing algae and more 25 species of animals. In this study the author observed that 2,4-D did not cause great impacts in the community and this is in agreement with previous studies that showed that this substance presents high LC-50 for several species. However, glyphosate had great impact in the community, causing a decrease of 22% of the species richness, while 2,4-D did not cause effects on this diversity. The authors also observed that neither of the two herbicides caused reduction in the periphyton biomass.
Reglone is a bypiridylium herbicide, whose active ingredient is diquat (1,1’-ethylene -2,2’-ipyridyl dibromide), and of foliar application, used to eliminate weeds of different crops [133]. Reglone, in the concentrations tested (0.005, 0.01, 0.05 and 0.1% of the active ingredient for
The herbicide Stomp 330, belongs to the dinitroanilines class, whose active ingredient is pendimethalin [N-(1-ethylpropyl)-2,6-dinitro-3,4-xylidine], it is applied as a systematic selective herbicide of the soil [133]. The responses of the two test systems for Stomp were very different: the concentrations tested (0.005, 0.1, 0.2 and 0.4% of the active ingredient for
Paraquat (1,1’-dimethyl-4-4’-bipyridium dichloride) is a non-selective herbicide with fast action, widely used worldwide, mainly in the pre-harvest of cotton and potato and also to control a broad spectrum of weeds [134, 135, 136]. According to Tortorelli et al. [134], paraquat is able to modify the activity of several enzymes of fish, affecting the cardiac contraction and opercular ventilation, effects that can alter the initial development of these organisms. According to Tomita et al. [137], paraquat causes oxidative stress in different species of fish by generating elevated levels of superoxide ion.
A study conducted by D’Souza et al. [138] evaluated the toxicity of the herbicide paraquat for germ cells of male Sprague-Dawley rats by dermal exposure to this chemical. The authors verified that paraquat, even at low doses, significantly reduced the amount of spermatozoa, increased the frequency of spermatozoa bearing abnormalities and the mortality rate of these germ cells, as well as affected the mobility of the spermatozoa of the individuals studied, showing that the herbicide is a cytotoxic and genotoxic agent for the germ cells of this organism.
Hanada [136], analyzing the karyotype of species of
According to Bus et al. [139], the genotoxic action of paraquat may be associated with the transference of a single electron of reduced oxygen to paraquat, forming superoxide ions. The singlet oxygen can be formed from the superoxide ion and subsequently react with lipids to form hydroperoxides and fatty acids. According to Tanaka and Amano [140], lipid peroxidation is responsible for the origin of several chromosome aberrations. Bauer Dial and Dial [141] still affirm that the oxidative stress induced by paraquat may be related to the teratogenic action of this compound to embryos and tadpoles of anurans.
Speit et al. [142] evaluated the genotoxic potential of the herbicide paraquat in Chinese hamster V79 cells, by chromosome aberrations and comet assays. Using a modified protocol of the comet assay with the modified protein FPG (formamidopyrimidine-DNA glycosylase), a repair enzyme that specifically nicks the DNA at sites of 8-oxo-guanines and formamidopyrimidines, it was not possible to detect oxidative damages in the bases of DNA after treatment with paraquat. Now, when the cells were treated directly on the slides, after lysis (i.e., after the cell membrane barrier has been eliminated), a significant increase in the migration of DNA was observed, only after treatment with high concentrations of the herbicide. Thus, the authors verified that the herbicide induced chromosome aberrations but was not able to induce relevant DNA lesions to promote mutations in the gene HPRT in cultured V79 cells.
Ribas et al. [135] assessed the cytotoxic, genotoxic and mutagenic potentials of different concentrations of the herbicide paraquat (0, 1, 5, 25, 50, 100, 250, 500, 1000, 2000 and 4000 µg/mL), by the assays of SCE, chromosome aberrations and micronuclei, in lymphocytes maintained in culture. The results showed that paraquat is an agent that induces cytotoxicity for lymphocytes, since it promoted the reduction in the nuclear division rate in all the concentrations tested and a significant decrease in the cell proliferation rates, when the cells were exposed to the highest concentration of the herbicide. In relation to the genotoxicity, the herbicide induced a significant increase in the frequencies of SCE of the lymphocytes treated, whose damage was not modified by co-treatment with the metabolic activation (S9 fraction of rat liver), but the data on the chromosome aberrations and micronuclei assays were not significant, which led the authors to conclude that paraquat is an inductor of primary damages in the DNA, although they have not shown that it has a clastogenic action.
A study performed by Hoffman and Eastin [143] evaluated the embryotoxic and teratogenic effects of two insecticides (lindane and toxaphene) and two herbicides (paraquat and 2,4,5-T), by external treatment of eggs of mallard duck (
The harmful effects of herbicides on human health are determined by several factors, such as the chemical class of those compounds, dose, time, and exposure route. Herbicides can be toxic to humans at high and lower doses [144]. The prolonged exposure can lead to a number of health effects, including the induction of diseases such as cancer and neurodegenerative [145, 146], reproductive and developmental changes [147] and respiratory effects [148].
Doll and Peto [149] estimated that 35% of all cases of cancer in the U.S. population originate from diet, and the herbicides present in foods are responsible. Estrogenicity assays made by Hernández et al. [150] show that organochlorine pesticides may act as endocrine disruption through more than one mechanism, including agonist or antagonist effects of different receptors. Chloro-s-triazize herbicides, pre-emergent pesticides used worldwide, have been generally considered as chemical compounds of low toxic potential for humans; however, there are many controversies on this issue. According to several international agencies, including the Environmental Protection Agency (EPA), Development for Environmental Assessment Center of the United States and IARC Monographs (International Agency for Research on Cancer), the herbicide atrazine, for example, was classified as a chemical agent probably carcinogenic to humans, although the basis for this conclusion is only evidenced in other animals [151, 152]. Due to the fact that atrazine induce mammary tumours in female Sprague-Dawley rats, the Peer Review Committee of the EPA Office of Pesticide Program (OPP) also concluded that atrazine should be considered in the Possibly Carcinogenic to Humans Group [153]. However, EPA [154] has classified this herbicide as a compound probably non carcinogenic to humans.
Some experimental studies have shown that exposure of humans to high doses of atrazine can result in an increased loss of body weight. However, a great number of epidemiological studies carried out with workers occupationally exposed to triazine herbicides indicate that these compounds do not have carcinogenic potential for these individuals. By analyses of different studies, it was observed that, although the chloro-s-triazine herbicides interfere in the endocrine responses of different species of mammals, their potential impact on humans seem to be mainly related to reproduction and development and not with human carcinogenesis [155].
Gammon et al. [83] discussed the extensive list of epidemiological studies with the herbicide atrazine, which describes that the carcinogenic potential of this compound to humans is not conclusive, although some studies have indicated a relationship between a high risk of prostate cancer and exposure to the herbicide.
Mladinic et al. [156] evaluated the genotoxic and mutagenic effects of low concentrations of the herbicides glyphosate and terbuthylazine, considered safe and, therefore, considered possible to occur in occupational and residential exposures (ADI – Acceptable Daily Intake, REL – Residential Exposure Level, OEL – Occupational Exposure Level, and 1/100 and 1/16 LD50 – Lethal Dose 50% - oral, rat), in human lymphocytes, with and without the use of metabolic activation (S9 fraction), by the FSH cytome assay, using pan-centromeric DNA probes to assess the content of micronuclei and other chromatinic instabilities. The authors verified that the frequencies of micronuclei, nuclear buds and nucleoplasmic bridges of cells treated with glyphosate slightly increased after the concentration of OEL 3.5 μg/mL, but no concentration induced an increase of the centromeric signals (C+) or DAPI (DAPI+). Now, the treatment with the herbicide terbuthylazine without metabolic activation showed a dose-response increase in the frequency of micronuclei of the lymphocytes exposed, and the significant data were from the concentration of 0.0008 µg/mL (REL) tested. The concentrations ADI (0.00058 µg/mL), REL (0.0008 µg/mL) and OEL (0.008 µg/mL) of terbuthylazine induced a significant occurrence of micronuclei hybridized with the centromeric probe (C+), regardless the presence or absence of S9, and of nuclear buds containing centromeric signals, only in the presence of S9. By the results obtained, it was suggested that the lowest concentrations of glyphosate do not have relevant harmful effects for the DNA molecule, while terbuthylazine presents a predominant aneugenic potential for the genetic material of human lymphocytes.
Terbuthylazine belongs to the chloro-s-triazine herbicides class, which inhibits the photosynthesis of weeds, by reaching the photosystem II. It is a chemical used for a variety of crops, such as maize, sugarcane, olive and pineapple [157]. Since the banishment of atrazine in European countries in 2006, terbuthylazine was recommended as its substitute. Due to the fact that the herbicide terbuthylazine is suspect of causing diseases in humans, such as non-Hodgkin lymphoma and lung cancer, Mladinic et al. [158] evaluated the effects of prolonged exposure (14 days) to low concentrations of this compound (0.58 ng/ml and 8 ng/ml) in human lymphocytes, using the comet assay and the comet-FISH assay (with the c-Myc and TP 53 genes). Treatment with terbuthylazine induced the migration of fragments of DNA in a significant manner, only for the highest concentration treated. The results showed an impairment of the structural integrity of c-Myc and TP 53, due to the prolonged exposure of human lymphocytes to terbuthylazine. The fact that several copies of TP53 were affected by the herbicide can indicate its ability to negatively interfere in the control of the cell cycle. However, the authors concluded that, for a more detailed assessment of the risk of cancer associated with exposure to terbuthylazine, it should be evaluated the impact of this pesticide on other housekeeping genes and markers.
Mladinic et al. [122] evaluated the genotoxic potential, by the comet assay and FISH, and oxidative damages, by the TBARS lipid peroxidation, of different concentrations of glyphosate (three similar to those observed in residential and occupational exposures and two related to LC50) in human lymphocytes. The comet assay showed that the concentration of 580 µg/mL promoted a significant increase in the tail length, while the concentration of 92.8 µg/mL caused an increase in the tail intensity, both in relation to the control test. With the addition of the S9 fraction, the tail length was significantly increased for all the concentrations tested. When the lymphocytes were exposed to the three highest concentrations without S9, there was an increase in the frequency of micronuclei, nuclear buds and nucleoplasmic bridges. The addition of a metabolic activation system only promoted a significant increase of the nuclear instabilities for the highest concentration tested. The values of TBARS significantly increased with the increase of the concentrations tested, regardless the presence or absence of the S9 fraction. Due to the fact that dose-dependent effects for all the assays used were not observed, the authors concluded that these concentrations of glyphosate are not relevant for human exposure, since they did not present a significant risk for human health.
According to Mladinic et al. [122], the increase in the number of crops genetically modified used in assays and diagnosis of resistance to glyphosate, may be related to the fact that these crops tolerate increasingly higher concentrations of the active ingredient necessary for an effective control of weeds, which results from the introduction of increasing amounts of glyphosate into the environment. Thus, some epidemiological studies have shown that human exposure to glyphosate present in the environment is correlated to the development of diseases such as the non-Hodgkin lymphoma [159, 160].
According to He et al. [161], paraquat, the second most widely used herbicide in the world, is able to selectively accumulate in human lungs by causing oxidative injury and fibrosis, leading several individuals to death. Chronic exposure to this herbicide is also associated with hepatic lesions, kidney failure and Parkinson´s disease [162, 163].
Studies carried out by He et al. [161] evaluated the toxicity of paraquat on BEAS-2B normal cells (human bronchial epithelial cells), showing that it is dose-dependent and results in mitochondrial damages, oxidative stress, death of lung cells exposed, as well as production of cytokines, pro-fibrogenic growth factors and transformation of myofibroblasts. The authors also proved that administration of resveratrol, a polyphenolic phytoalexin naturally produced by several plants, to control bacteria and fungi, was able to inhibit the production of reactive oxygen species, inflammations and fibrotic reactions induced by paraquat, by the activation of the Nrf2 signaling (Nuclear Factor Erythroid-2), revealing a new molecular mechanism for the intervention against oxidative damages and pulmonary fibrosis resulted from the action of toxic chemical compounds.
The study on the influence of a complex mixture of herbicides (atrazine, 2,4-D, alachlor, ciazine and malathion) in workers occupationally exposed to them, was carried out using cytogenetic methods standardly established (chromosome aberrations and micronucleus assay) and the comet assay technique. This assay showed a significant increase in the DNA migration (P<0.001), suggesting that long-term exposure to the pesticides could cause damages in the genome of somatic cells and, therefore, would represent a potential risk to human health [164].
The authors present in this manuscript the bioassays and the test-systems most commonly used to evaluate the effects of herbicides and the test-organisms to best suit the assessments of herbicide effects. In these considerations, the authors attempted to present the most sensitive and efficient organisms capable of detecting environmental contamination resulting from the action of these chemical agents. Additionally, we present in this paper the need to carry out research aimed at more effective methods to prevent and/or reduce the deleterious effects of such compounds on the environment, the biota potentially exposed, and especially to human health.
In this study it was addressed several studies that used different methodologies, which evaluated the toxicity and action of herbicides on different non-target organisms, including human species. The table below summarizes the main researches addressed in the text.
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
Atrazine | \n\t\t\tErythrocytes of Nile tilapia ( | \n\t\t\tmicronucleus test; comet assay | \n\t\t\tincrease in the DNA fragmentation; induction of micronuclei and nuclear abnormalities in all tested concentrations | \n\t\t\t6.25, 12.5, 25 µg/L | \n\t\t\t[8] Ventura et al., 2008 | \n\t\t
Atrazine | \n\t\t\tWild leopard frogs ( | \n\t\t\ttoxicity assay | \n\t\t\tinduction of abnormalities in the gonads; developmental delay and hermaphroditism (≥ 0.1ppb) | \n\t\t\t0.01, 0.1, 0.4, 0.8, 1, 10, 25, 200 ppb | \n\t\t\t[82] Hayes et al., 2002 | \n\t\t
Atrazine | \n\t\t\t\n\t\t\t\t | \n\t\t\tchromosome aberration assay | \n\t\t\tinduction of multinucleated, aneuploid and polyploid cells; abnormalities in the mother cells of pollen grains; meiotic instability | \n\t\t\t2.7 Kg a.i./ha | \n\t\t\t[80] Liang et al., 1967 \n\t\t\t | \n\t\t
Atrazine | \n\t\t\tHuman lymphocytes | \n\t\t\tchromosome aberration assay | \n\t\t\tincrease in the chromosome aberrations frequency at 0.10 ppm | \n\t\t\t0.01, 1, 0.10 mg/ml | \n\t\t\t[85] Meisner et al., 1992 | \n\t\t
Atrazine | \n\t\t\tHuman lymphocytes | \n\t\t\tchromosome aberration assay; SCE | \n\t\t\tincrease in the frequency of chromosome aberrations; increase in the frequency of sister chromatid exchange in all tested concentrations | \n\t\t\t5, 8.5, 17, 51 µM | \n\t\t\t[93] Lioi et al., 1998 | \n\t\t
Atrazine | \n\t\t\tHuman blood cells | \n\t\t\tchromosome aberration assay | \n\t\t\tSignificant increase of chromosome breaks | \n\t\t\t1 ppm | \n\t\t\t[94] Meisner et al., 1993 | \n\t\t
Atrazine | \n\t\t\tRat | \n\t\t\tchromosome aberration assay | \n\t\t\tthere was no significant increase in the frequency of chromosome aberrations at 20 ppm | \n\t\t\t20 ppm | \n\t\t\t[85] Meisner et al., 1992 | \n\t\t
Atrazine | \n\t\t\tBone marrow cells of rats | \n\t\t\tchromosome aberration assay | \n\t\t\tthere was no significant increase in the frequency of chromosome aberrations | \n\t\t\t20 ppm | \n\t\t\t[86] Roloff et al., 1992 | \n\t\t
Atrazine | \n\t\t\tHuman lymphocytes | \n\t\t\tchromosome aberration assay | \n\t\t\tinduction of chromosome aberrations | \n\t\t\t0.0001 µg/mL | \n\t\t\t[94] Meisner et al., 1993 | \n\t\t
Atrazine | \n\t\t\tRat leukocytes | \n\t\t\tcomet assay | \n\t\t\tincrease in the damages in the DNA for 500 mg/Kg | \n\t\t\t125, 250, 500 mg/Kg | \n\t\t\t[89] Tennant et al., 2001 | \n\t\t
Atrazine | \n\t\t\tErythrocytes of bullfrog tadpoles | \n\t\t\tcomet assay | \n\t\t\tsignificant increase in the DNA damages, from the concentration of 4.8 mg/L | \n\t\t\t4.8, 19.75, 77, 308 mg/L | \n\t\t\t[90] Clements et al., 1997 \n\t\t\t | \n\t\t
Atrazine | \n\t\t\tHuman lymphocytes | \n\t\t\tcomet assay | \n\t\t\tsignificant increase in the DNA damages, mainly at the concentrations of 100 and 200 µg/L | \n\t\t\t50, 100, 200 µg/L | \n\t\t\t[69] Ribas et al., 1995 | \n\t\t
Atrazine | \n\t\t\tHepatocytes of Wistar rats | \n\t\t\tlipid peroxidation assay; micronucleus test | \n\t\t\tincrease in the rates of lipid peroxidation, hepatic damages, death of hepatocytes and induction of micronuclei. | \n\t\t\t400 ppm | \n\t\t\t[91] Campos-Pereira et al., 2012 | \n\t\t
Atrazine | \n\t\t\tErythrocytes and gill cels of the fish | \n\t\t\tmicronucleus test; comet assay | \n\t\t\tinduction of damages in the DNA and micronuclei, in the tested concentrations, in all the exposure periods (from 1 to 35 days), with more significant effects in the highest concentrations and exposure periods; higher sensitivity for gill cells | \n\t\t\t4.24, 5.30. 8.48 mg/L | \n\t\t\t[22] Nwani et al., 2011 | \n\t\t
Atrazine | \n\t\t\tErythrocytes of the gibel carp fish ( | \n\t\t\tmicronucleus test; comet assay | \n\t\t\tsignificant induction of DNA strand breaks and micronuclei, in all tested concentrations of the commercial product (Gesaprim), but there was not a induction of these genotoxic and mutagenic effects for the active ingredient. | \n\t\t\t5, 10, 15 µg/L | \n\t\t\t[84] Çavas, 2011 | \n\t\t
Atrazine | \n\t\t\tHuman lymphocytes | \n\t\t\tcomet assay | \n\t\t\tsignificant increase of damage in the DNA exposed to the commercial product Gesaprim, but there was no induction of genotoxicity for the active ingredient atrazine, for all tested concentrations. | \n\t\t\t0.047, 0.47, 4.7 ug/L | \n\t\t\t[101] Zeljezic et al., 2006 | \n\t\t
Atrazine | \n\t\t\tSomatic cells of | \n\t\t\tchromosome aberration assay; micronucleus test | \n\t\t\tsignificant inhibition of the mitotic index, significant increase in the frequencies of micronuclei and chromosome aberrations of both test organisms, when exposed to the commercial product Gesaprim, but there was no induction of any significant effects when cells were exposed to the active ingredient atrazine, for all tested concentrations. | \n\t\t\t\n\t\t\t\t | \n\t\t\t[102] Srivastava and Mishra, 2009 | \n\t\t
Atrazine | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tthere was no significant induction of genotoxic damages nor mutagenic | \n\t\t\t1 – 1000 µg/plate | \n\t\t\t[92] Ruiz and Marzin, 1997 | \n\t\t
Atrazine | \n\t\t\tSprague-Dawley rats | \n\t\t\tembryotoxic and teratogenic tests | \n\t\t\tinduction of hypospadias in male newborns at 200 ppm and diverse embryotoxic damages at 25 ppm. | \n\t\t\t25, 100, 200 mg/kg/d | \n\t\t\t[87] Wu et al., 2007 | \n\t\t
Atrazine | \n\t\t\tWistar rats | \n\t\t\tRadioimmunoassay | \n\t\t\talterations in the levels of testosterone, androstenedione, estradiol, estrone, progesterone and corticosterone to 50 or 200 ppm for 60 days | \n\t\t\t50, 200 mg / kg / day | \n\t\t\t[88] Modic et al., 2004 \n\t\t\t | \n\t\t
Atrazine, Simazine and Cyanazine | \n\t\t\tHuman lymphocytes | \n\t\t\tchromosome aberration assay and SCE | \n\t\t\tthere was no significant increase of chromosome aberrations and sister chromatid exchanges | \n\t\t\t0.5, 5, 50 ppb | \n\t\t\t[104] Kligerman et al., 1993 | \n\t\t
Atrazine, Simazine and Cyanazine | \n\t\t\tPolychromatic erythrocytes of the bone marrow of female C57B1/6 rats | \n\t\t\tmicronucleus test | \n\t\t\tthere was no significant induction of micronuclei | \n\t\t\t0, 125, 250, 500 mg/kg | \n\t\t\t[103] Kligerman et al., 2000 | \n\t\t
Atrazine, Simazine and Cyanazine | \n\t\t\tChinese Hamster Ovary – CHO – cells | \n\t\t\tflow cytometry assay | \n\t\t\tsignificant induction of chromosome damages by atrazine for the tested concentrations, proven clastogenic potential of cyanazine | \n\t\t\t0.003 µg/mL, 0.018 µg/mL(atrazine); 0.003 µg/mL, 0.012 µg/mL (cyanazine) | \n\t\t\t[107] Taets et al., 1998 | \n\t\t
Atrazine and Butachlor | \n\t\t\tGreen alga | \n\t\t\tacute toxicity assay | \n\t\t\tatrazine is highly toxic for | \n\t\t\t\n\t\t\t\t | \n\t\t\t[20] He et al., 2012 | \n\t\t
Butachlor | \n\t\t\tAlpine cricket frog ( | \n\t\t\tchromosome aberration assay | \n\t\t\taffected the survival, development and metamorphosis time of tadpoles in different concentrations; DNA damage (0.4-0.8 mg/L) | \n\t\t\tranging from 0.025 to 3.2 mg/l | \n\t\t\t[43] Liu et al., 2011 | \n\t\t
Terbutryn | \n\t\t\tHuman leukocytes | \n\t\t\tmicronucleus test; comet assay; SCE | \n\t\t\tthere was no significant induction of micronuclei and SCE; significant induction of DNA damages for all tested concentrations | \n\t\t\t0, 5, 10, 50, 100, 150 µg/mL | \n\t\t\t[108] Moretti et al., 2002 | \n\t\t
2,4-D | \n\t\t\t\n\t\t\t\t | \n\t\t\ttoxicity assay | \n\t\t\tdose-dependent reduction in the response of the simpatic junction to nerve stimulation due to inhibition of the glandular chloride channel in mucosa skin | \n\t\t\t0.01, 0.1, 1 mM | \n\t\t\t[114] Suwalsky et al., 1999 | \n\t\t
2,4-D | \n\t\t\tGills of different species of fishes | \n\t\t\ttoxicity assay | \n\t\t\tbleeding, renal increase, impairment of the renal functions and hepatic degeneration | \n\t\t\t400 mg/L | \n\t\t\t[115] Gómez et al., 1998 | \n\t\t
2,4-D | \n\t\t\tChinese Hamster Ovary – CHO – cells | \n\t\t\tSCE | \n\t\t\tsignificant increase in the sister chromatid exchange at 2 and 4 µg/ml | \n\t\t\t2, 4, 6, 10 µg/mL | \n\t\t\t[116] González et al., 2005 | \n\t\t
2,4-D | \n\t\t\tBone marrow and germ cells of rats | \n\t\t\tSCE | \n\t\t\tsignificant increase in the sister chromatid exchange at 100 and 200 ppm, for both cell types | \n\t\t\t50,100, 200 mg/kg | \n\t\t\t[117] Madrigal-Bujaidar et al.,2001 | \n\t\t
2,4-D | \n\t\t\tFrog | \n\t\t\tFETAX - frog embryo teratogenic assay | \n\t\t\tsignificant induction of embryotoxic and teratogenic effects | \n\t\t\t245 mg/L | \n\t\t\t[119] Morgan et al., 1996 | \n\t\t
2,4-D and Butachlor | \n\t\t\tErythrocytes of the catfish ( | \n\t\t\tchromosome aberration assay; micronucleus test | \n\t\t\tsignificant increase in the frequency of micronuclei and altered cells in a dose-response manner for both herbicides | \n\t\t\t2,4-D: 25, 50, 75ppm; Butachlor: 1, 2, 2.5ppm | \n\t\t\t[113] Ateeq et al., 2002 | \n\t\t
2,4-D and Paraquat | \n\t\t\tRainbow trout ( | \n\t\t\tacute lethality test, lipid peroxidation assay by quantification of MDA; comet assay | \n\t\t\ttoxic action more evident for paraquat (high indices of mortality); apnea and white spots in the scales of individuals exposed to the 2 herbicides; increase in the rates of MDA and damages in the DNA after exposure to all concentrations of the tested herbicides | \n\t\t\t2,4-D: 316, 346, 389, 436, 489 mg/L; Paraquat: 0.055, 0.066, 0.083, 0.116, 0.133 mg/L | \n\t\t\t[112] Martínez-Tabche et al., 2004 | \n\t\t
2,4-D and 2,4-D DMA | \n\t\t\tHumanh lymphocytes and erythrocytes | \n\t\t\tSCE; analysis of the cell cycle progression and mitotic index | \n\t\t\talterations in the cell cycle and induction of SCE for some concentrations only with more significant genotoxic effects for erythrocytes | \n\t\t\t10, 25, 50, 100 µg/mL | \n\t\t\t[118] Soloneski et al., 2007 | \n\t\t
2,4-D; Triclopyr; Diquat dibromide; glyphosate | \n\t\t\tRainbow trout ( | \n\t\t\tVitellogenin estrogenic assay | \n\t\t\tsignificant increase in the levels of vitellogenin of the plasma of fishes exposed to 2,4-D | \n\t\t\t0.11, 1.64, 2.07, 1.25 mg/L | \n\t\t\t[120] Xie et al., 2005 | \n\t\t
Glyphosate | \n\t\t\t\n\t\t\t\t | \n\t\t\tmicrobial growth assay | \n\t\t\tinhibition of microbial growth by the commercial product Roundup; microbiocide effect at concentrations lower than the recommended by agricultural use for the commercial product Roundup; non induction of significant toxic effects for the three microorganisms by the active ingredient glyphosate | \n\t\t\t0.1, 1, 10, 100, 1000, 10000 ppm | \n\t\t\t[127] Clair et al., 2012 | \n\t\t
Glyphosate | \n\t\t\tTadpoles of wood frog ( | \n\t\t\tacute toxicity assay \n\t\t\t\t \n\t\t\t\t \n\t\t\t | \n\t\t\tsignificant induction of morphological alterations of tadpoles of the three species; for the wood frogs and leopard frogs, exposure to glyphosate affected the size of the tail of tadpoles, for all tested concentrations | \n\t\t\t0, 1, 2, or 3 mg acid equivalents [a.e.] /L of Roundup Original MAX | \n\t\t\t[128] Relyea, 2012 | \n\t\t
Glyphosate | \n\t\t\tRoots from the smooth hawksbeard ( | \n\t\t\tchromosome aberration assay; micronucleus assay | \n\t\t\tthere was no induction of genotoxic and/or mutagenic effects for any of the species | \n\t\t\t\n\t\t\t\t | \n\t\t\t[129] Dimitrov et al., 2006 | \n\t\t
Glyphosate | \n\t\t\tFemale Wistar rats | \n\t\t\tacute toxicity assay; teratogenicity assay | \n\t\t\thigh mortality index of females treated with the highest concentration of the commercial product Roundup; increase in the dose-response of fetal skeletal alterations | \n\t\t\t500, 750, 1000 mg/kg | \n\t\t\t[130] Dallegrave et al., 2003 \n\t\t\t | \n\t\t
Glyphosate | \n\t\t\tHuman lymphocytes | \n\t\t\tcomet assay; FISH; lipid peroxidation assay – TBARS | \n\t\t\tsignificant increase in the DNA migration at 580 µg/mL; significant increase of the comet tail intensity at 92.8 µg/mL; greater lesion in the DNA in the presence of S9; increase in the frequency micronuclei, nuclear buds and nucleoplasmic bridges, without S9; significant increase of nuclear instabilities in the highest concentration tested with S9; significant dose-response increase of the levels of TBARS | \n\t\t\t0.5, 2.91, 3.5, 92.8, 580 µg/mL | \n\t\t\t[122] Mladinic et al., 2009 | \n\t\t
Glyphosate adn 2,4-D | \n\t\t\tAlgae and 25 species of aquatic animals | \n\t\t\tacute toxicity assay | \n\t\t\tthere was no reduction in the biomass of periphyton by the 2 herbicides; there was no great impacts to the aquatic community by 2,4-D; high impact to the aquatic community by glyphosate by the significative decrease in the species richness | \n\t\t\t0, 1, 2, or 3 mg acid equivalents [a.e.] /L of Roundup Original MAX | \n\t\t\t[132] Relyea, 2005 | \n\t\t
Glyphosate and Terbuthylazine | \n\t\t\tHuman lymphocytes | \n\t\t\tcytome FISH | \n\t\t\tglyphosate caused an increase in the frequencies of micronuclei, nuclear buds and nucleoplasmic bridges of clells treated (3.5 µg/mL onward), but without induction of centromeric signals; terbuthylazine induced an increase in the frequency of micronuclei hybridized with centromeric probe and nuclear buds with centromeric signals in the presence of S9 (0.008 ug/mL onward) | \n\t\t\t0.5, 2.91, 3.50, 92.8, 580 µg/mL (glyphosate); 0,00058, 0,0008, 0,008, 25, 156,5 µg/mL (terbuthylazine) | \n\t\t\t[156] Mladinic et al., 2009 | \n\t\t
Terbuthylazine | \n\t\t\tHuman lymphocytes | \n\t\t\tcomet assay; comet assay-FISH | \n\t\t\tinduction of the migration of fragments of DNA, significant only at the highest concentration; impairment of the structural integrity of c-Myc and TP 53 due to prolonged exposure to terbuthylazine | \n\t\t\tTerbuthylazine: 0.58 ng/ml, 8 ng/ml; carbofuran: 8 ng/ml, 21.6 ng/ml | \n\t\t\t[158] Mladinic et al., 2012 | \n\t\t
Paraquat | \n\t\t\tSeveral species of fishes | \n\t\t\tacute toxicity assay; enzyme activity assay | \n\t\t\talteration in the activity of different enzymes; negative effects on cardiac contraction and opercular ventilation | \n\t\t\t0.1-2.0 mg/L | \n\t\t\t[134] Tortorelli et al., 1990 | \n\t\t
Paraquat | \n\t\t\tSeveral species of fishes | \n\t\t\tenzyme activity assay | \n\t\t\tinduction of oxidative stress; increase in the levels of SOD | \n\t\t\t0.2-50 mM | \n\t\t\t[137] Tomita et al., 2007 | \n\t\t
Paraquat | \n\t\t\tGerm cells of Sprague-Dawley rats | \n\t\t\tcytotoxicity assay | \n\t\t\treduction in the quantity of spermatozoa; increase in the mortality rates and abnormalities in spermatozoa for the higher concentrations | \n\t\t\t0, 6, 15, 30 mg/kg | \n\t\t\t[138] D’Souza et al., 2006 | \n\t\t
Paraquat | \n\t\t\tLeukocytes of | \n\t\t\tconventional cytogenetics assay | \n\t\t\tgenotoxic effects, such as chromosome breaks | \n\t\t\t10-6 M | \n\t\t\t[136] Hanada, 2011 | \n\t\t
Paraquat | \n\t\t\tHuman lymphocytes | \n\t\t\tchromosome aberration assay; micronucleus test; SCE | \n\t\t\treduction in the cell division index; decrease in the cell proliferation rates; significant increase in the frequencies of SCE (50 µg/mL for 24h treatment; 4000 µg/mL for 2h treatment), significant increase in the MN frequencies (concentrations ≥ 25 µg/mL) | \n\t\t\t0, 1, 5, 25, 50, 250, 500, 1000, 2000, 4000 µg/mL | \n\t\t\t[135] Ribas et al., 1998 | \n\t\t
Paraquat | \n\t\t\tBEAS 2B normal cells (human bronchial epithelial cells) | \n\t\t\tcytotoxicity assay, oxidative stress assay | \n\t\t\tmitochondrial damage; oxidative stress; cell death; production of cytokines, pro-fibrogenic growth facts and transformation of myofibroblast | \n\t\t\t10 uM | \n\t\t\tHe et al., 2012 | \n\t\t
Diuron | \n\t\t\tPacific oyster ( | \n\t\t\ttoxicity assay | \n\t\t\tirreversible damages to the genetic material, negative impacts in the reproduction of aquatic organisms | \n\t\t\t300 ng/L, 3 µg/L | \n\t\t\t[44] Bouilly et al., 2007 | \n\t\t
Diquat | \n\t\t\tRoots of smooth hawksbeard ( | \n\t\t\tchromosome aberration test; micronucleus test | \n\t\t\tthere was no induction of chromosome aberrations for any test system; significant increase of the frequency of micronuclei for both test systems | \n\t\t\t\n\t\t\t\t | \n\t\t\t[129] Dimitrov et al., 2006 | \n\t\t
Pendimethalin | \n\t\t\tRoots of smooth hawksbeard ( | \n\t\t\tchromosome aberration test; micronucleus test | \n\t\t\tthere was no significant increase in the frequencies of chromosome aberrations in plant cells, but an increase of their incidence in cells of rats; significant increase in the frequency of micronuclei for both test systems. | \n\t\t\t\n\t\t\t\t | \n\t\t\t[129] Dimitrov et al., 2006 | \n\t\t
Simetryn, mefenacet and thiobencarb | \n\t\t\t\n\t\t\t\t | \n\t\t\ttoxicity assay | \n\t\t\ttoxic effects for tadpoles, more significant for thiobencarb | \n\t\t\tThiobencarb: 6.85-2.92 mM | \n\t\t\t[42] Saka, 2010 | \n\t\t
Complex mixture of pesticides (atrazine, 2,4-D, alachlor, ciazine and malathion) | \n\t\t\tWorkers exposed \n\t\t\t | \n\t\t\tchromosome aberration assay; micronucleus test; comet assay | \n\t\t\tsignificant increase in the migration of the DNA | \n\t\t\tMixture of various concentrations of pesticides | \n\t\t\t[163] Garaj-Vrhovac and Zeljezic, 2002 | \n\t\t
List o the main researches carried out with several bioindicators to evaluate the toxicity of herbicides.
Coronavirus Disease 19 (Covid-19) marked the years 2020 and 2021 with its very fast diffusion rates and severity. With the quick development of vaccines against the disease, the pandemic right now seems to come to an end. Yet, living the last 2 years with a contagious disease has left some serious questions: What is the role of socio–economic determinants in the transmission of an airborne contagious disease like Covid–19? What factors are most influential and make countries more vulnerable to such diseases? What is the role of spatiality in the spread? In this study, we aim to investigate the answers to these questions for Turkey. More specifically, we try to point out the most influential socio–economic factors in the spread of Covid-19 in Turkey in a spatial setting.
The first Covid-19 case is confirmed in Turkey on 11th March 2020 in İstanbul. It spread quickly all over the country. To limit its transmission among the Turkish provinces, similar strategies to other countries, such as travel restrictions and partial curfews, were applied in the initial days. Yet, in time, it has become clear that every country has its own dynamics that limit the effectiveness of precautions against the Covid-19. For example, [1] find that the extreme poverty level is an important determinant in the national performance of low– and middle–income countries, since it determines the ability of social distancing. They also note that the disadvantaged share of the population in terms of socio–economic status is more vulnerable to contagious diseases. Therefore, each country must be assessed individually to understand its needs and to be prepared for future diseases. Analyzing the spread of the Covid-19 and the socio–economic determinants behind is important to be ready for any country as well as Turkey.
The ties between the socio–economic status in the spread of Covid-19 were discussed previously in the literature. These studies mainly focus on mainland China [2, 3] and the USA [4, 5]. Some of them compare the national performances of many countries based on the socio–economic variables, (e.g., [6, 7, 8]). Yet, as [4] clearly state, “
Ref. [11] emphasize the role of spatiality in the analysis of contagious diseases by stating that “
Although the importance of location in the transmission process of such diseases besides the other risk factors is mentioned heavily in the literature, studies considering geography in the Covid-19 incidence rates are scarce and they mostly make a choice between the spatial autoregressive model (SAR) and spatial error model (SEM). [15], for example, attempts to determine the socio-economic and region-specific in the Covid-19 transmission in German counties with a choice between SAR and SEM specifications. [16] examine the local transmission of Covid-19 cases in the USA. Again, they made a selection between SAR and SEM based on the Lagrange Multiplier (LM) tests. [17] employ SAR, SEM, and SAC models to detect the Covid-19 period prevalence in the US counties. [4] consider several demographic factors and income as well as air pollution and health-related variables in order to explain the spread of Covid-19 in the US states. They also employ a SAR model. [18] use the number of confirmed new cases in mainland China as the dependent variable where the recovered cases and the rate of deaths are the explanatory variables in a spatial panel setting. He compares SEM and SAR models, but cannot show spatiality in the explanation of the rate of new cases. He concludes that the spatial lag of X (SLX) model fits the nature of local spillovers in this association for China.
The situation for the scarce studies that consider the spread of Covid-19 in Turkey from a spatial perspective is parallel to the world literature. [8] provides an exploratory spatial analysis with different weight matrices for Turkish Covid-19 cases and deaths in which high spatial autocorrelation is detected particularly for major Turkish provinces. Similarly, [19] use Moran I and Local Indicator Spatial Association (LISA) statistics to determine the hot and cold spots among Turkish provinces. [20] examine the effects of a group of socio–economic determinants as well as climate–based variables on the number of Covid-19 cases with SEM and SAR specifications. [21] looks at the relationship between centrality in terms of trade, transportation, and health and the number of cases in a Turkish province while considering other socioeconomic factors as control variables. For this aim, he employs SAR and SAC models. [22] use the impact of population density, elderly dependency ratio, Gross Domestic Product (GDP) per capita, literacy rate, and health capacity variables to explain the diffusion of Covid-19 in Turkey with a SAR model. They find global spillovers and significant coefficients for population density and elderly dependency ratio while explaining the increase in the Covid-19 cases.
With this study, we also contribute to the scarce literature on Covid-19 studies in Turkey with a spatial perspective. One of the novelties of this paper comes from the spatial model it adopts. Unlike the previous spatial studies on Covid-19 diffusion, we argue that a spatial Durbin model (SDM) must be the first model to adopt for the analysis. The SDM approach is well known for containing both the global and local spillovers at the same time, which is a feature of the Covid-19 pandemic. In fact, when the best describing model is unknown, [23] suggests using SDM as a starting point as well. As a result, we start our analysis with an SDM setting to detect the local and global spillovers in the diffusion of Covid-19 cases across 81 Turkish provinces. Different from the existing studies, we use the vaccination rates and sub–indicators of Life Index in Provinces by the Turkish Statistical Institute (TSI) as the explanatory variables. Life Index in Provinces report includes 41 sub–indicators about income, work life, safety, housing, environment, social life, access to infrastructure services, education, life satisfaction, and civic engagement. By using these sub–indicators, we believe that every aspect of socioeconomic status in Turkish provinces, from per km2 green area to health capacity, can be taken into account. Hence, an exhaustive list of variables that have the potential to impact the spread of Covid-19 is considered. Controlling the vaccination rates also allows us to detect its role among other variables and its impact on the spread of the disease. By doing so, we are able to contribute to the very limited literature on Covid-19 vaccine hesitancy.
To the extent of our knowledge, a similar study to our setting that examines the spread of Covid-19 in Turkey belongs to [24]. He employs 11 leading indicators of the Life Index in Provinces report, not the sub–indicators as well as other socioeconomic and environmental variables such as GDP, household size, age, air quality, humidity, and average temperature. Although this study also mentions the spatial distribution of Covid-19 cases in Turkey and benefits from some spatial maps, the main analysis method is Ordinary Least–Squares (OLS), not spatial models. By using spatial analysis methods with an exhaustive set of socioeconomic indicators, we believe that our study closes an important gap in the literature.
Our results indicate no significant global impacts in the spread of Covid-19 cases across Turkey, but significant local interactions. We show that vaccination in a given province decreases the total number of cases per hundred thousand people in the same province, but increases the Covid-19 cases in the neighboring province. This seemingly puzzling finding is a result of vaccine hesitancy toward Covid-19 vaccines. The “
Based on the findings of this study, we can suggest that the usage of clear communication channels with society has vital importance in fighting against infectious diseases. In this way, it is possible to correct the misperceptions both about the nature of the disease and the vaccinations. Overconfidence about the health status and vaccine hesitancy might increase the overall number of cases, so the burden on the health care system.
The rest of the study continues with an explanation of the data and methodology utilized. The next section presents our findings. The last section concludes with the policy suggestions to the Turkish authorities for the next pandemics.
This study uses the total number of confirmed COVID-19 cases per 100,000 population from 81 Turkish provinces as the dependent variable. This data is publicly available and reported as weekly averages by the Turkish Ministry of Health.
To be able to determine which explanatory variables might be important in the spread of Covid-19, we examine thoroughly the previous literature that applies both a spatial and non-spatial analysis. [25] argue economic variables like wealth or income are the main drivers of the person-to-person spread of infectious diseases such as COVID-19. [26] demonstrate that low literacy has been influential in the spread of the disease. [17, 27] find that age is effective on the spread of COVID-19 cases. Population and population density were also noted as significant variables by [15, 25, 28, 29]. The number of doctors and the number of hospital beds are considered important factors by [3, 25, 26] because their availability has the potential to draw more COVID-19 patients to the area. Living in an urban vs. rural area might be another determinant in the spread of cases as noted by [25, 29]. [15] also considers household size as a factor. Social life indicators and average space available per household are used by [25].
We proxy the socioeconomic and health status of each province that is noted in the literature by using the Life Index in Provinces provided by the Turkish Statistical Institute in 2016. This index is produced based on the approach of the OECD Better Life Index. The aim of the Life Index in Provinces is to compare the well–being and living quality of Turkish provinces as well as their economic status. To do so, 11 leading indicators and 41 sub–indicators that include both objective and subjective aspects of life are created. These indicators include income, work life, safety, housing, environment, social life, access to infrastructure services, education, life satisfaction, and civic engagement dimensions. Based on the previous literature, we select explanatory variables among the 41 sub–indicators. The dimensions that can affect the spread of Covid-19 but are not captured by the Life Index in Provinces, such as median age, percentage of individuals 65 years old and above, or population density are also added to the analysis.
Besides the socio–economic factors, the vaccine uptake decision of societies is a crucial weapon against the spread of Covid-19. Therefore, we use the vaccination rates for individuals 18 years old and above for each province as a control variable in the models.
A summary of explanatory variables that are employed in this analysis and the data sources are reported in Table 1.
Variable | Proxy | Source |
---|---|---|
COVID-19 variables | Total number of cases per 100,000 population by Turkish provinces | Turkish Ministry of Health (weekly) |
Percentage of 18+ population vaccinated against COVID-19 at least once by Turkish provinces | Turkish Ministry of Health (daily) | |
Housing Conditions | Number of rooms per person | Life Index in Provinces by Turkish Statistical Institute (2016) |
The household size in Turkish provinces | Turkish Statistical Institute (2020) | |
Work Life | Employment Rate | Life Index in Provinces by Turkish Statistical Institute (2016) |
Unemployment Rate | Life Index in Provinces by Turkish Statistical Institute (2016) | |
Average Daily Earnings | Life Index in Provinces by Turkish Statistical Institute (2016) | |
Income and Wealth | Percentage of Households in middle and higher Income Groups | Life Index in Provinces by Turkish Statistical Institute (2016) |
Percentage of Households declaring to fail on meeting basic needs | Life Index in Provinces by Turkish Statistical Institute (2016) | |
GDP per capita by Turkish provinces | Turkish Statistical Institute (2013) | |
Health | Infant Mortality Rate | Life Index in Provinces by Turkish Statistical Institute (2016) |
Life Expectancy at Birth | Life Index in Provinces by Turkish Statistical Institute (2016) | |
Satisfaction Rate with Health Status | Life Index in Provinces by Turkish Statistical Institute (2016) | |
Health Capacity Index | Turkish Ministry of Health, Health Statistics (2018) | |
Education | Percentage of higher education graduates | Life Index in Provinces by Turkish Statistical Institute (2016) |
Safety | Murder Rate | Life Index in Provinces by Turkish Statistical Institute (2016) |
Percentage of people feeling safe when walking alone at night | Life Index in Provinces by Turkish Statistical Institute (2016) | |
Civic engagement | Voter turnout at local administrations | Life Index in Provinces by Turkish Statistical Institute (2016) |
Rate of membership to political parties | Life Index in Provinces by Turkish Statistical Institute (2016) | |
Percentage of persons interested in union/association activities | Life Index in Provinces by Turkish Statistical Institute (2016) | |
Access to Infrastructure Services | Number of internet subscriptions (per hundred persons) | Life Index in Provinces by Turkish Statistical Institute (2016) |
Social life | Number of cinema and theater audiences (per hundred persons) | Life Index in Provinces by Turkish Statistical Institute (2016) |
Shopping mall area per thousand people (m2) | Life Index in Provinces by Turkish Statistical Institute (2016) | |
Satisfaction rate with social relations | Life Index in Provinces by Turkish Statistical Institute (2016) | |
Median Age | Median of individuals’ age in Turkish provinces | Turkish Statistical Institute (2020) |
Age 65+ | Percentage of population over 65 + by Turkish provinces | Turkish Statistical Institute (2020) |
Population | Population density of Turkish provinces | Turkish Statistical Institute (2019) |
Socioeconomic and Covid–19 related variables and the data sources.
The data period is determined by the announcement periods of the Turkish Ministry of Health. Vaccination rates started to be announced at the province level on 04.07.2021 on a daily basis. The total number of cases per 100,000 population is announced weekly. Therefore, we consider the average total number of cases and vaccination rates for July 2021 in this analysis.
A standard OLS model is often estimated as a reference for the following spatial models. This study employs the same starting point. To understand the effect of location on the Covid-19 cases, many studies employ SAR and SEM specifications. [2] note that the SAR model will show how the infection burden in a location is affected by the infection burden in the neighboring locations. SEM is used to understand whether the OLS residuals are correlated to residuals of the neighboring locations. In the lines of [2, 3] also consider a SAC model. They argue that since the SAC model contains a spatial lag and a spatial error term, it can be seen as a combination of these two.
In fact, the spatial model family has a large set of approaches1, and model selection is a crucial part of its applications. [4] argues that this selection must be based on the spillover type that the economic theory points out. Unlike [2]‘s suggestion, [4] stresses that the SAC model is not the linear combination of SAR and SEM approaches. Not considering the spillover types in the selection of appropriate spatial models leads us to the identification problem noted in [5].
[6] state that the locations that are closer to the center of the pandemic are affected more quickly than the distant ones. However, besides geographical proximity, Covid-19 can spread easily when the locations are connected on a network, such as traveling. It means that both global and local spillovers exist in the diffusion of infectious diseases. We argue in this paper that this nature of Covid-19 can be best captured with an SDM approach. [7] also recommends using SDM as a departure point, when the true data generating process, as in the case of Covid-19, is unknown. SDM will also give the linear combination of SAR and SEM specifications [4], as intended by [2, 3].
The OLS model that is used as a benchmark is presented in Eq. (1).
where
The SDM specification that is used in this paper is shown in Eq. (2).
In Eq. (2), the dependent and the explanatory variables are the same as the OLS model defined in Eq. (1). However, here, we scale both the dependent and explanatory variables with a spatial weight matrix (W). The coefficient
Our model selection process follows [7] and we also compare our results with SAR and SLX specifications. The SAR and SLX models are shown in Eq. (3) and Eq. (4) respectively.
The spatial weight matrix used throughout all these models is the same. The elements of W take the value of 1 if two Turkish provinces are neighbors, and zero otherwise.
First, we examine the spatial variation of the total number of cases in Turkey. The spread of Covid-19 cases across Turkish provinces is shown in Figure 1.
The variation of Covid-19 cases across provinces in Turkey in July 2021.
The map in Figure 1 demonstrates that there are regional variations in the diffusion of Covid-19 cases. The total number of confirmed cases increases from west to east of Turkey. We also consider the four main regions of Turkey and statistically compare the average cases in these regions. These regions are defined as follows:
We begin our analysis with the classical OLS model. By excluding the insignificant variables at the 10% level, we refine the model and obtain the ultimate model. We check the OLS assumptions. We find heteroskedasticity in our main model which might be a result of spatial dependency.
As explained before, since the association between the total number of cases and the various socioeconomic variables is not well discussed in the previous literature, we start with an SDM specification to avoid the omitted variable problem [23], which is also the linear combination of SAR and SEM specifications [30]. However, the SDM specification does not show significant results. The LR tests comparing SDM vs. OLS and SAR vs. OLS cannot reject the null hypothesis of no significant global interactions. The lack of significant global spillovers indicates that the burden of the disease at one location is not affected by the burden of the disease in the neighboring locations. Yet, the LR test for the coefficients of local interactions in the SDM specification is significant at the 1% level (LR test is 52.5983, and the p–value is 0.0015). That is to say, although no global impacts can be detected in the transmission process of Covid-19 cases in Turkey, geography still matters in the form of local interactions. The socioeconomic features of neighboring provinces are influential on the spread of Covid-19 in a given province. This finding is in line with the study by [18] in which an SLX model is found appropriate to model the new cases in mainland China. Therefore, following [23], we continue our analysis with an SLX model. The final SLX model and the OLS model as a benchmark are shown in Table 2.
(1) | (2) | |
---|---|---|
Final OLS Model | Final SLX Model | |
Vaccine Rate | −1.5737*** | −1.3693** |
(0.5605) | (0.5926) | |
Membership to Political Parties | 2.0558 | 3.2805** |
(1.5622) | (1.5043) | |
satisfaction rate with social relations | −2.1859 | −2.2772*** |
(1.6857) | (0.7206) | |
satisfaction rate with health status | 3.4398 | 3.3891** |
(2.6869) | (1.6631) | |
Constant | −21.0895 | −26.1843 |
(117.8685) | (105.4470) | |
W*Vaccine Rate | 4.9654*** | |
(1.7096) | ||
W* Median Age | −10.2514*** | |
(3.4318) | ||
AIC | 870.386 | 874.219 |
Adjusted R2 | 0.2341 | |
Number of Observations | 81 | 81 |
The impact of socioeconomic variables on the total cases of Covid-19: OLS and SLX models.
Vaccination is clearly the strongest weapon in the fight against Covid-19. The findings from Table 2 also confirm this situation and reveal that the vaccination rate and the total number of cases are significantly and negatively related. Interestingly, it is found that the effect of vaccination rates in the neighboring provinces is positive and significant. That is, the increased rates of vaccination in the neighboring locations cause a growth in the total number of cases in a given province. This result seems puzzling at first, but it can be explained by the vaccine hesitancy concept. Vaccine hesitancy is defined as the “delay in acceptance or refusal of vaccination despite the availability of vaccination services” [31]. [32] state that the vaccine uptake decision of an individual can be dependent on the actions of the neighbors. They call this concept
We also show that as the satisfaction rate with health status increases, the number of total cases also rises in a particular province. This finding can be attributed to the fact that Covid-19 is mostly perceived as an older people’s disease or only dangerous for people with co–morbidities. To fight this perception, World Health Organization (WHO) made many announcements, including the one that the Chief of WHO explained that “
The rate of membership to political parties is an indicator of civic engagement. As this variable has a higher rate, the social relations, and connections increase as well. This would make it difficult to keep the social distance and adapt to “stay at home” calls. Our findings in Table 2 confirm this result and demonstrate a positive effect of this variable on the total number of cases.
Median age, itself, is not a determinant of the spread of Covid-19 cases across Turkish provinces. However, the median age of the neighbors negatively impacts the number of cases in a given province. This finding is in line with [15]. He notes that the increase in the median age of neighbors reduces the social interactions with the given state and traveling, so less spread has occurred.
The satisfaction rate with social relations is a proxy for social life. Our results indicate that the higher values of this variable are related to a lower level of total cases. It seems that people who are more satisfied with their social life are most likely to keep their social distance and less engaged with many people. This finding might be explained by the existence of video–calls and other telecommunication methods. Individuals may meet their social needs via the internet and stay at home at the same time.
We cannot show any significant effect of housing conditions, work life, income and wealth, or health indicators other than health status, education, safety, and access to infrastructure services, however.
The results of this paper once more emphasize the importance of vaccinations in order to control the number of cases. In the case of such infectious diseases, governments must use clear communication channels with society to avoid misperceptions about the nature of the disease or the precautions to avoid further spread. Our findings show that over–confidence about the individual health status and vaccine hesitancy increase the number of total cases, so the burden on the health care system.
This study employs an exhaustive set of socioeconomic variables and vaccination rates to detect their roles in the spread of Covid-19 in Turkey in a spatial setting. Province-level data allows us to detect the existence of spatiality as well. We cannot detect any global interactions in the diffusion process, so the number of infected people at one location does not bring an extra infection burden to the neighboring locations. Yet, our findings show that local interactions in terms of vaccination rates and median age play an important role in the increase in the total number of cases. Increased vaccination rates in the neighboring provinces also increase the total number of cases in a given province. This result can be explained by the vaccine hesitancy toward the Covid-19 vaccine. We also find evidence that people that are more satisfied with their health status are more likely to catch the disease and increase the total number of cases. To fight the misperceptions about the nature of the disease and the vaccination procedure, the Turkish government must adopt a clear–communication policy and actively work for individuals to access reliable information.
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These reactions occur through a regular radical chain causing growth of polymer by three steps, namely, initiation, propagation, and termination. To understand ionizing radiation-induced polymerization, the water radiolysis must be taken into consideration. This chapter explores the mechanism of water molecules radiolysis paying especial attention to the basic regularities of solvent radicals’ interaction with the polymer molecules for forming the crosslinked polymer. Water radiolysis is the main engine of the polymerization processes, especially the “free-radical polymerization.” The mechanisms of the free-radical polymerization and crosslinking will be discussed in detail later. Since different polymers respond differently to radiation, it is useful to quantify the response, namely in terms of crosslinking and chain scission. A parameter called the G-value is frequently used for this purpose. It represents the chemical yield of crosslinks, scissions and double bonds, etc. For the crosslinked polymer, the crosslinking density increases with increasing the radiation dose, this is reflected by the swelling degree of the polymer while being immersed in a compatible solvent. If crosslinking predominates, the crosslinking density increases and the extent of swelling decreases. If chain scission predominates, the opposite occurs. 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The natural resources are limited, and due to the natural disasters like sudden and severe abiotic stress factors, excessive floods, etc., the production capacities are changed per year. In contrast, the yield potential should be significantly increased to cope with this problem. Despite rich genetic diversity, manipulation of the cultivars through alternative techniques such as mutation breeding becomes important. Radiation is proven as an effective method as a unique method to increase the genetic variability of the species. Gamma radiation is the most preferred physical mutagen by plant breeders. Several mutant varieties have been successfully introduced into commercial production by this method. Combinational use of in vitro tissue culture and mutation breeding methods makes a significant contribution to improve new crops. Large populations and the target mutations can be easily screened and identified by new methods. Marker assisted selection and advanced techniques such as microarray, next generation sequencing methods to detect a specific mutant in a large population will help to the plant breeders to use ionizing radiation efficiently in breeding programs.",book:{id:"5451",slug:"new-insights-on-gamma-rays",title:"New Insights on Gamma Rays",fullTitle:"New Insights on Gamma Rays"},signatures:"Özge Çelik and Çimen Atak",authors:[{id:"147362",title:"Dr.",name:"Özge",middleName:null,surname:"Çelik",slug:"ozge-celik",fullName:"Özge Çelik"},{id:"147364",title:"Prof.",name:"Çimen",middleName:null,surname:"Atak",slug:"cimen-atak",fullName:"Çimen Atak"}]},{id:"32846",doi:"10.5772/36950",title:"Current Importance and Potential Use of Low Doses of Gamma Radiation in Forest Species",slug:"current-importance-and-potential-use-of-low-doses-of-gamma-radiation-in-forest-species",totalDownloads:5301,totalCrossrefCites:2,totalDimensionsCites:13,abstract:null,book:{id:"1590",slug:"gamma-radiation",title:"Gamma Radiation",fullTitle:"Gamma Radiation"},signatures:"L. 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In this chapter, the following aspects of radiation treatment process are considered: sources of contamination and major contaminants of water and wastewater; primary processes in aqueous systems initiated by ionizing radiation; principal ways of contaminant conversion as consequences of primary processes (complete mineralization of organic compounds, partial decomposition of organic molecules resulted in detoxification, decolorization, disinfection of polluted water, and improvement in biological degradation of contaminant, polymerization of monomers’ contaminants, oxidation-reduction processes, and coagulation of colloids); sources of ionizing radiation; and main equipment applied in radiation technologies of aqueous system purification.",book:{id:"6149",slug:"ionizing-radiation-effects-and-applications",title:"Ionizing Radiation Effects and Applications",fullTitle:"Ionizing Radiation Effects and Applications"},signatures:"Igor E. Makarov and Alexander V. 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These reactions occur through a regular radical chain causing growth of polymer by three steps, namely, initiation, propagation, and termination. To understand ionizing radiation-induced polymerization, the water radiolysis must be taken into consideration. This chapter explores the mechanism of water molecules radiolysis paying especial attention to the basic regularities of solvent radicals’ interaction with the polymer molecules for forming the crosslinked polymer. Water radiolysis is the main engine of the polymerization processes, especially the “free-radical polymerization.” The mechanisms of the free-radical polymerization and crosslinking will be discussed in detail later. Since different polymers respond differently to radiation, it is useful to quantify the response, namely in terms of crosslinking and chain scission. A parameter called the G-value is frequently used for this purpose. It represents the chemical yield of crosslinks, scissions and double bonds, etc. For the crosslinked polymer, the crosslinking density increases with increasing the radiation dose, this is reflected by the swelling degree of the polymer while being immersed in a compatible solvent. If crosslinking predominates, the crosslinking density increases and the extent of swelling decreases. If chain scission predominates, the opposite occurs. A further detailed discussion of these aspects is presented throughout this chapter.",book:{id:"6149",slug:"ionizing-radiation-effects-and-applications",title:"Ionizing Radiation Effects and Applications",fullTitle:"Ionizing Radiation Effects and Applications"},signatures:"Mohamed Mohamady Ghobashy",authors:[{id:"212371",title:"Dr.",name:"Mohamed",middleName:null,surname:"Mohamady Ghobashy",slug:"mohamed-mohamady-ghobashy",fullName:"Mohamed Mohamady Ghobashy"}]},{id:"53780",title:"Gamma-Ray Spectrometry and the Investigation of Environmental and Food Samples",slug:"gamma-ray-spectrometry-and-the-investigation-of-environmental-and-food-samples",totalDownloads:2529,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Gamma radiation consists of high‐energy photons and penetrates matter. This is an advantage for the detection of gamma rays, as gamma spectrometry does not need the elimination of the matrix. The disadvantage is the need of shielding to protect against this radiation. Gamma rays are everywhere: in the atmosphere; gamma nuclides are produced by radiation of the sun; in the Earth, the primordial radioactive nuclides thorium and uranium are sources for gamma and other radiation. The technical enrichment and use of radioisotopes led to the unscrupulously use of radioactive material and to the Cold War, with over 900 bomb tests from 1945 to 1990, combined with global fallout over the northern hemisphere. The friendly use of radiation in medicine and for the production of energy at nuclear power plants (NPPs) has caused further expositions with ionising radiation. This chapter describes in a practical manner the instrumentation for the detection of gamma radiation and some results of the use of these techniques in environmental and food investigations.",book:{id:"5451",slug:"new-insights-on-gamma-rays",title:"New Insights on Gamma Rays",fullTitle:"New Insights on Gamma Rays"},signatures:"Markus R. Zehringer",authors:[{id:"311750",title:"Dr.",name:"Markus R.",middleName:null,surname:"Zehringer",slug:"markus-r.-zehringer",fullName:"Markus R. Zehringer"}]},{id:"54118",title:"Gamma Rays from Space",slug:"gamma-rays-from-space",totalDownloads:2089,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"An overview of gamma rays from space is presented. We highlight the most powerful astrophysical explosions, known as gamma-ray bursts. The main features observed in detectors onboard satellites are indicated. In addition, we also highlight a chronological description of the efforts made to observe their high energy counterpart at ground level. Some candidates of the GeV counterpart of gamma-ray bursts, observed by Tupi telescopes, are also presented.",book:{id:"5451",slug:"new-insights-on-gamma-rays",title:"New Insights on Gamma Rays",fullTitle:"New Insights on Gamma Rays"},signatures:"Carlos Navia and Marcel Nogueira de Oliveira",authors:[{id:"189908",title:"Dr.",name:"Carlos",middleName:null,surname:"Navia",slug:"carlos-navia",fullName:"Carlos Navia"},{id:"243084",title:"MSc.",name:"Marcel",middleName:null,surname:"De Oliveira",slug:"marcel-de-oliveira",fullName:"Marcel De Oliveira"}]}],onlineFirstChaptersFilter:{topicId:"227",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82739",title:"Experimental Breeder Reactor II",slug:"experimental-breeder-reactor-ii",totalDownloads:12,totalDimensionsCites:0,doi:"10.5772/intechopen.105800",abstract:"The Experimental Breeder Reactor II (EBR-II) operated from 1964 to 1994. EBR-II was a sodium-cooled fast reactor operating at 69 MWth producing 19 MWe. Rather than using a loop approach for the coolant, EBR-II used a pool arrangement where the reactor core, primary coolant piping, and primary reactor coolant pumps were contained within the pool of sodium. Also contained within the pool was a heat exchanger where primary coolant, which is radioactive, transferred heat to secondary, nonradioactive, sodium. The nuclear power plant included a sodium boiler building where heat from the secondary sodium generated superheated steam, which was delivered to a turbine/generator for electricity production. EBR-II fuel was metallic uranium alloyed with various metals providing significant performance and safety enhancements over oxide fuel. The most significant EBR-II experiments occurred in April 1986. Relying on inherent physical properties of the reactor, two experiments were performed subjecting the reactor to loss of primary coolant flow without reactor SCRAM and loss of the secondary system heat removal without reactor SCRAM. In both experiments, the reactor experienced no damage. This chapter provides a description of the most important design features of EBR-II along with a summary of the landmark reactor safety experiments.",book:{id:"10982",title:"Nuclear Reactors - Spacecraft Propulsion, Research Reactors, and Reactor Analysis Topics",coverURL:"https://cdn.intechopen.com/books/images_new/10982.jpg"},signatures:"Chad L. Pope, Ryan Stewart and Edward Lum"},{id:"82712",title:"Idaho State University AGN-201 Low Power Teaching Reactor: An Overlooked Gem",slug:"idaho-state-university-agn-201-low-power-teaching-reactor-an-overlooked-gem",totalDownloads:10,totalDimensionsCites:0,doi:"10.5772/intechopen.105799",abstract:"A category of reactors called university research and teaching reactors, includes relatively high-power pool-type and low-power solid-core reactors. Many high-power university reactors are largely used for irradiations and isotope production. Their almost constant operation tends to impede student access. A university reactor can be particularly relevant to the university’s mission of preparing well-rounded students who have theoretical knowledge, reinforced by focused laboratory reactor experience. The solid-core Idaho State University Aerojet General Nucleonics (AGN) model 201 reactor operates at such a low power (5 W maximum) that it is not useful for isotope production activities. However, the AGN-201 reactor is well suited for teaching and research activities. The solid-core AGN-201 reactor requires no active cooling system, uses a simple shielding arrangement, and the very low operating power results in trivial burnup providing an operating lifetime exceeding many decades. It is thus worthwhile to examine the Idaho State University AGN-201 nuclear reactor more closely because it offers a wide range of research and teaching capabilities while being widely available to students.",book:{id:"10982",title:"Nuclear Reactors - Spacecraft Propulsion, Research Reactors, and Reactor Analysis Topics",coverURL:"https://cdn.intechopen.com/books/images_new/10982.jpg"},signatures:"Chad L. Pope and William Phoenix"},{id:"81424",title:"Core Reload Analysis Techniques in the Advanced Test Reactor",slug:"core-reload-analysis-techniques-in-the-advanced-test-reactor",totalDownloads:13,totalDimensionsCites:0,doi:"10.5772/intechopen.103896",abstract:"Since becoming a national user facility in 2007, the type of irradiation campaigns the Advanced Test Reactor (ATR) supports has become much more diverse and complex. In prior years, test complexity was limited by the computational ability to analyze the tests’ influence on the fuel. Large volume tests are irradiated in flux traps which are designed to receive excess neutrons from the surrounding fuel elements. Typically, fuel elements drive the test conditions, not vice versa. The computational tool, PDQ, was used for core physics analysis for decades. The PDQ code was adequate so long as the diffusion approximation between test and fuel element remained valid. This paradigm changed with the introduction of the Ki-Jang Research Reactor—Fuel Assembly Irradiation (KJRR-FAI) in 2015. The KJRR-FAI was a prototypic fuel element for the KJRR research reactor project in the Republic of Korea. The KJRR-FAI irradiation presented multiple modeling and simulation challenges for which PDQ was ill suited. To demonstrate that the KJRR-FAI could be irradiated and meet safety requirements, the modern neutron transport codes, HELIOS and MCNP, were extensively verified and validated to replace PDQ. The hybrid 3D/2D methodology devised with these codes made analysis of the ATR with KJRR-FAI possible. The KJRR-FAI was irradiated in 2015-2016.",book:{id:"10982",title:"Nuclear Reactors - Spacecraft Propulsion, Research Reactors, and Reactor Analysis Topics",coverURL:"https://cdn.intechopen.com/books/images_new/10982.jpg"},signatures:"Samuel E. Bays and Joseph W. Nielsen"},{id:"81555",title:"Nuclear Thermal Propulsion",slug:"nuclear-thermal-propulsion",totalDownloads:118,totalDimensionsCites:0,doi:"10.5772/intechopen.103895",abstract:"This chapter will cover the fundamentals of nuclear thermal propulsion systems, covering basic principles of operation and why nuclear is a superior option to chemical rockets for interplanetary travel. It will begin with a historical overview from early efforts in the early 1950s up to current interests, with respect to fuel types, core materials, and ongoing testing efforts. An overview will be provided of reactor types and design elements for reactor concepts or testing systems for nuclear thermal propulsion, followed by a discussion of nuclear thermal design concepts. A section on system design and modeling will be presented to discuss modeling and simulation of driving phenomena: neutronics, materials performance, heat transfer, and structural mechanics, solved in a tightly coupled multiphysics system. Finally, it will show the results of a coupled physics model for a conceptual design with simulation of rapid startup transients needed to maximize hydrogen efficiency.",book:{id:"10982",title:"Nuclear Reactors - Spacecraft Propulsion, Research Reactors, and Reactor Analysis Topics",coverURL:"https://cdn.intechopen.com/books/images_new/10982.jpg"},signatures:"Mark D. DeHart, Sebastian Schunert and Vincent M. Labouré"},{id:"81013",title:"Cyber-Informed Engineering for Nuclear Reactor Digital Instrumentation and Control",slug:"cyber-informed-engineering-for-nuclear-reactor-digital-instrumentation-and-control",totalDownloads:33,totalDimensionsCites:0,doi:"10.5772/intechopen.101807",abstract:"As nuclear reactors transition from analog to digital technology, the benefits of enhanced operational capabilities and improved efficiencies are potentially offset by cyber risks. Cyber-Informed Engineering (CIE) is an approach that can be used by engineers and staff to characterize and reduce new cyber risks in digital instrumentation and control systems. CIE provides guidance that can be applied throughout the entire systems engineering lifecycle, from conceptual design to decommissioning. In addition to outlining the use of CIE in nuclear reactor applications, this chapter provides a brief primer on nuclear reactor instrumentation and control and the associated cyber risks in existing light water reactors as well as the digital technology that will likely be used in future reactor designs and applications.",book:{id:"10982",title:"Nuclear Reactors - Spacecraft Propulsion, Research Reactors, and Reactor Analysis Topics",coverURL:"https://cdn.intechopen.com/books/images_new/10982.jpg"},signatures:"Shannon Eggers and Robert Anderson"},{id:"79671",title:"Fault Detection by Signal Reconstruction in Nuclear Power Plants",slug:"fault-detection-by-signal-reconstruction-in-nuclear-power-plants",totalDownloads:107,totalDimensionsCites:0,doi:"10.5772/intechopen.101276",abstract:"In this work, the recently developed auto associative bilateral kernel regression (AABKR) method for on-line condition monitoring of systems, structures, and components (SSCs) during transient process operation of a nuclear power plant (NPP) is improved. The advancement enhances the capability of reconstructing abnormal signals to the values expected in normal conditions during both transient and steady-state process operations. The modification introduced to the method is based on the adoption of two new approaches using dynamic time warping (DTW) for the identification of the time position index (the position of the nearest vector within the historical data vectors to the current on-line query measurement) used by the weighted-distance algorithm that captures temporal dependences in the data. Applications are provided to a steady-state numerical process and a case study concerning sensor signals collected from a reactor coolant system (RCS) during start-up operation of a NPP. The results demonstrate the effectiveness of the proposed method for fault detection during steady-state and transient operations.",book:{id:"10982",title:"Nuclear Reactors - Spacecraft Propulsion, Research Reactors, and Reactor Analysis Topics",coverURL:"https://cdn.intechopen.com/books/images_new/10982.jpg"},signatures:"Ibrahim Ahmed, Enrico Zio and Gyunyoung Heo"}],onlineFirstChaptersTotal:8},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:141,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:123,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:22,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"24",title:"Sustainable Development",doi:"10.5772/intechopen.100361",issn:"2753-6580",scope:"\r\n\tGlobally, the ecological footprint is growing at a faster rate than GDP. This phenomenon has been studied by scientists for many years. However, clear strategies and actions are needed now more than ever. Every day, humanity, from individuals to businesses (public and private) and governments, are called to change their mindset in order to pursue a virtuous combination for sustainable development. Reasoning in a sustainable way entails, first and foremost, managing the available resources efficiently and strategically, whether they are natural, financial, human or relational. In this way, value is generated by contributing to the growth, improvement and socio-economic development of the communities and of all the players that make up its value chain. In the coming decades, we will need to be able to transition from a society in which economic well-being and health are measured by the growth of production and material consumption, to a society in which we live better while consuming less. 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