Saturated fatty acids of general formula CH3(CH2)n COOH.
\r\n\tThis book plans to focus on elaborating recent advances in the field of electrodeposition with fruitful evidence. The feasibility of electrodeposition routes to fabricate different metals and their derivatives for various uses are to be explained in detail.
",isbn:null,printIsbn:"979-953-307-X-X",pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"207613e28b728f2b6cd3007e746cdefa",bookSignature:"Prof. Dhanasekaran Vikraman and Dr. K. Karuppasamy",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/8532.jpg",keywords:"Topic 1:Thin films\r\nKeywords: Electrodeposition, Anodic deposition, cathodic deposition, Reaction kinetics\r\nTopic 2: Metals and metal oxides \r\nKeywords: II-VI elements, copper oxide, Ferrous oxide, Silver oxide\r\nTopic 3: Chalcogens \r\nKeywords: metal dichalcogens\r\nTopic 4: Alloys\r\nKeywords: Metal alloys, Solid solution, Gold - copper, Iron - Cobalt",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"August 14th 2019",dateEndSecondStepPublish:"September 4th 2019",dateEndThirdStepPublish:"November 3rd 2019",dateEndFourthStepPublish:"January 22nd 2020",dateEndFifthStepPublish:"March 22nd 2020",remainingDaysToSecondStep:"2 years",secondStepPassed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"199404",title:"Prof.",name:"Dhanasekaran",middleName:null,surname:"Vikraman",slug:"dhanasekaran-vikraman",fullName:"Dhanasekaran Vikraman",profilePictureURL:"https://mts.intechopen.com/storage/users/199404/images/system/199404.jpeg",biography:"Dr. Dhanasekaran Vikraman is an Assistant Professor in Division of Electronics and Electrical Engineering, Dongguk University-Seoul, Seoul, Korea. He received his Bachelor's degree at Mannai Rajagopalaswamy Govt. Arts College, Mannargudi, affiliated to Bharathidasan University, Tiruchirappalli, India. After that, he completed his Master and Ph.D degrees at Department of Physics, Alagappa University, India. Later, he received visiting scientist position at KIST, Korea; Marie-Curie Experienced Researcher fellowship at Department of Physics, Aristotle University of Thessaloniki, Greece; and Post-Doc positions at Sejong University and Ajou University, Korea. \r\nHe has authored more than 100 international journal articles and 1 book chapter. In addition, he served as an Editor with IntechOpen for a book entitled “Design, Simulation and Construction of Field Effect Transistors”. His research interests are mainly focused on low-cost synthesis of inorganic materials and 2D-materials for electronics and energy applications.",institutionString:"Dongguk University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Dongguk University",institutionURL:null,country:{name:"Korea, South"}}}],coeditorOne:{id:"300938",title:"Dr.",name:"K.",middleName:null,surname:"Karuppasamy",slug:"k.-karuppasamy",fullName:"K. Karuppasamy",profilePictureURL:"https://mts.intechopen.com/storage/users/300938/images/system/300938.jpeg",biography:"Dr. K. Karuppasamy is currently working as an Assistant professor at Division of Electronics & Electrical Engineering, Dongguk University-Seoul, South Korea. He received his Ph.D. in the field of nanocomposite electrolytes for lithium-ion batteries in Anna University, Chennai, India in 2014. Later, he completed his Post-Doc positions at Department of Metallurgical Engineering and Materials Science, Indian Institute of Technology Bombay, India, and Department of Chemical Engineering, Sogang University, Seoul, South Korea. His research interests mainly focus on synthesis and characterization of nanostructured materials for energy storage and conversion device applications. He has published more than 50 research papers in well reputed international journals and also authored for 25 international and national conference papers.",institutionString:"Dongguk University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Dongguk University",institutionURL:null,country:{name:"Korea, South"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"8",title:"Chemistry",slug:"chemistry"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"297737",firstName:"Mateo",lastName:"Pulko",middleName:null,title:"Mr.",imageUrl:"https://mts.intechopen.com/storage/users/297737/images/8492_n.png",email:"mateo.p@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"6695",title:"Design, Simulation and Construction of Field Effect Transistors",subtitle:null,isOpenForSubmission:!1,hash:"304929bc541d961dff8977432a49075e",slug:"design-simulation-and-construction-of-field-effect-transistors",bookSignature:"Dhanasekaran Vikraman and Hyun-Seok Kim",coverURL:"https://cdn.intechopen.com/books/images_new/6695.jpg",editedByType:"Edited by",editors:[{id:"199404",title:"Prof.",name:"Dhanasekaran",surname:"Vikraman",slug:"dhanasekaran-vikraman",fullName:"Dhanasekaran Vikraman"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophanides",surname:"Theophile",slug:"theophanides-theophile",fullName:"Theophanides Theophile"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"878",title:"Phytochemicals",subtitle:"A Global Perspective of Their Role in Nutrition and Health",isOpenForSubmission:!1,hash:"ec77671f63975ef2d16192897deb6835",slug:"phytochemicals-a-global-perspective-of-their-role-in-nutrition-and-health",bookSignature:"Venketeshwer Rao",coverURL:"https://cdn.intechopen.com/books/images_new/878.jpg",editedByType:"Edited by",editors:[{id:"82663",title:"Dr.",name:"Venketeshwer",surname:"Rao",slug:"venketeshwer-rao",fullName:"Venketeshwer Rao"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4816",title:"Face Recognition",subtitle:null,isOpenForSubmission:!1,hash:"146063b5359146b7718ea86bad47c8eb",slug:"face_recognition",bookSignature:"Kresimir Delac and Mislav Grgic",coverURL:"https://cdn.intechopen.com/books/images_new/4816.jpg",editedByType:"Edited by",editors:[{id:"528",title:"Dr.",name:"Kresimir",surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"55693",title:"Fatty Acids and Their Analogues as Anticancer Agents",doi:"10.5772/intechopen.68171",slug:"fatty-acids-and-their-analogues-as-anticancer-agents",body:'Plants, animals and microbes generally contain even number of carbon atoms in straight chains, with a carboxylic group at one end and double bonds with cis configuration on the another end. The chain length of the common fatty acids varies between 14 and 22, but on occasions can span between 2 and 36 or even more in animal tissues. Fatty acids found in animal tissues have one to six double bonds, whereas those in algae have up to five bonds. Higher plants rarely have more than three, whereas microbial fatty acids occasionally have more than one. The fatty acids, which are derived from triglycerides or phospholipids, have a chain of 4–28 carbons. Fatty acids, which are not attached to other molecules, are known as free fatty acids which on breakdown yield large quantities of ATP. Many cell types use either glucose or fatty acids for this purpose. In particular, heart and skeletal muscle prefer fatty acids [1].
Fatty acids may be monounsaturated, polyunsaturated or saturated (Figure 1). They help in moving oxygen through the blood stream to all parts of the body, aid cell membrane development and strengthen the organs and tissue. They also help in healthy skin and prevent early ageing and more importantly help rid the arteries of cholesterol build‐up.
Naturally occurring fatty acids.
Saturated fatty acids are straight‐chain compounds with 14, 16 and 18 carbon atoms. The most abundant saturated fatty acids found in animal and plant tissues are esterified with odd‐ and even‐numbered homologues with 2–36 carbon atoms. A list of common saturated fatty acids together with their trivial names and shorthand designations is given in Table 1.
S. no. | Systematic name | Shorthand designation | Trivial name |
---|---|---|---|
1. | Ethanoic | 2:0 | Acetic |
2. | Butanoic | 4:0 | Butyric |
3. | Hexanoic | 6:0 | Caproic |
4. | Octanoic | 8:0 | Caprylic |
5. | Nonanoic | 9:0 | Pelargonic |
6. | Decanoic | 10:0 | Capric |
7. | Undecanoic | 11:0 | – |
8. | Dodecanoic | 12:0 | Lauric |
9. | Tridecanoic | 13:0 | – |
10. | Tetradecanoic | 14:0 | Myristic |
11. | Pentadecanoic | 15:0 | Myristic |
12. | Hexadecanoic | 16:0 | Palmitic |
13. | Heptadecanoic | 17:0 | Margaric |
14. | Octadecanoic | 18:0 | Stearic |
15. | Nonadecanoic | 19:0 | Margaric |
16. | Arachidic | 20:0 | Eicosanoic |
17. | Heneicosanoic | 21:0 | – |
18. | Docosanoic | 22:0 | Behenic |
19. | Tetracosanoic | 24:0 | Lignoceric |
Saturated fatty acids of general formula CH3(CH2)n COOH.
Monoenoic fatty acids are straight‐chain fatty acids containing 10–30 carbon atoms with one cis‐double bond. The double bond can be in different positions and this is specified in the systematic nomenclature in relation to the carboxyl group (Table 2).
S. no. | Systematic name | Shorthand designation | Trivial name |
---|---|---|---|
1. | cis‐9‐Tetradecenoic | 14:1(n‐5) | Myristoleic |
2. | cis‐9‐Hexadecenoic | 16:1(n‐7) | Palmitoleic |
3. | trans‐3‐Hexadecenoic | – | – |
cis‐6‐Octadecenoic | 18:1(n‐12) | Petraselenic | |
4. | cis‐9‐Octadecenoic | 18:1(n‐9) | Oleic |
5. | cis‐11‐Octadecenoic | 18:1(n‐7) | cis‐Vaccenic |
6. | trans‐11‐Octadecenoic | – | Elaidic |
7. | cis‐9‐Eicosenoic | 20:1(n‐11) | Gadoleic |
8. | cis‐11‐Octadecenoic | 18:1(n‐9) | Gondic |
9. | cis‐13‐Docosenoic | 22:1(n‐9) | Erucic |
10. | cis‐15‐Tetracosenoic | 24:1(n‐9) | Nervonic |
Monoenoic fatty acids of general formula CH3(CH2)mCH=CH(CH2)nCOOH.
Polyunsaturated fatty acids (PUFAs) are fatty acids which contain multiple double bonds and are subdivided into families according to their derivation from specific biosynthetic precursors. In each instance, the families contain between two and six cis‐double bonds separated by single methylene\\ groups, and have the same terminal structure [2]. A list of some of the important PUFAs is presented in Table 3.
S. no. | Systematic name | Shorthand designation | Trivial name |
---|---|---|---|
1. | 9,12‐Octadecadienoic* | 18:2(n‐6) | Linoleic |
2. | 6,9,12‐Octadecatrienoic | 18:3(n‐6) | γ‐Linolenic |
3. | 8,11,14‐Eicosatrienoic | 18:3(n‐6) | Homo‐γ‐linolenic |
4. | 5,8,11,14‐Eicosatetraenoic | 20:4(n‐6) | Arachidonic |
5. | 4,7,10,13,16‐Eicosapentaenoic | 20:5(n‐6) | – |
6. | 9,12,15‐Octadecatrienoic | 18:3(n‐6) | α‐Linolenic |
7. | 5,8,11,14,17‐Eicosapentaenoic | 20:5(n‐3) | EPA |
8. | 7,10,13,16,19‐Docosapentaenoic | 22:5(n‐3) | – |
9. | 4,7,10,13,16,19‐Docosahexaenoic | 22:5(n‐3) | DHA |
10. | 5,8,11‐Eicosatrienoic | 20:3(n‐9) | Mead’s acid |
Polyunsaturated fatty acids of general formula CH3 (CH2)m(CH=CHCH2)x(CH2) n COOH.
*The double bond configuration in each instance is cis.
Branched‐chain fatty acids, which occur widely in nature, are present as minor components except in bacteria, where they appear to replace unsaturated fatty acids functionally. The branch consists of a single methyl group, either on the penultimate (iso) or on the antepenultimate (anteiso) carbon atoms [3, 4].
A large number of hydroperoxy, hydroxyl and epoxy fatty acids (eicosanoids) are formed enzymatically as intermediates in the biosynthesis of prostanoids. A large number of hydroxy fatty acids occur in seed oils, and the best known of these is ricinoleic acid which is the principle constituent of castor oil. Polyhydroxy fatty acids are present in plant cutins, shellacs and many seed oils.
The biological fatty acids are of different lengths, the last position is labelled as omega (ω). Omega‐3 fatty acids are long‐chain polyunsaturated fatty acids (18–22 carbon atoms) with the first of many double bonds beginning with the third carbon atom. However, omega‐6 fatty acids have the first of many double bonds beginning with the sixth carbon atom. Alpha‐linolenic acid (ALA) and linoleic acid (LA) are the parent compounds of the omega‐3 family and omega‐6 family of fatty acids, respectively.
Although the International panel of lipid experts says the ideal ratio of omega‐3 to omega‐6 essential fatty acids is approximately 1:1, still we follow the ratio 20:1 in our diet [5]. Long‐chain polyunsaturated fatty acids cannot be formed de novo but can be synthesized from the essential fatty acids like linoleic acid and alpha‐linolenic acid. These two essential fatty acids are desaturated and lengthened progressively by microsomal enzyme systems to form highly unsaturated, long‐chained fatty acids such as arachidonic acid and docosahexaenoic acid (DHA). The omega‐3 and omega‐6 fatty acids are not interconvertible. Dietary fish and fish oil supplements are a direct source of omega‐3 fatty acids and dietary oils have large quantity of omega‐6 fatty acids [6].
Yonesawa and co‐workers carried out the inhibitory effect of conjugated eicosapentaenoic acid (cEPA) on mammalian DNA polymerase and topoisomerase activities and human cell proliferation. They found that the inhibitory effect of cEPA was stronger than that of the non‐conjugated EPA and suggested the therapeutic potential of cEPA as a leading anticancer compound that poisons mammalian DNA polymerase (POLS) [7]. The work carried by Unduri revealed the tumouricidal and antiangiogenic actions of gamma‐linolenic acid (GLA) and its derivatives. It was found that GLA being an endogenous naturally occurring molecule had no significant side effects [8]. Paul et al. reported that the long‐chain eicosapentaenoic acid (EPA) and docosahexaenoic acids (DHA) have been consistently shown to inhibit the proliferation of breast and prostate cancer cell lines in vitro and to reduce the risk and progression of these tumours in animal experiments. Many investigations revealed that the above‐said fatty acids inhibit cyclooxygenase‐2 and the oxidative metabolism of arachidonic acid (AA) to PGE2. EPA and DHA also have been shown to inhibit lipoxygenase which metabolizes AA to hydroxyl eicosatetraenoic acids and leucotrienes which suppress apoptosis, stimulate angiogenesis and stimulate tumour cell division (Figure 2). Further, they explained that the n‐3 PUFAs potentially affect carcinogenesis by specific mechanisms [9]. These mechanisms are as follows: (1) alteration of the response of immune system to cancer cells through the suppression of arachidonic acid (AA, 20:4n‐6)‐derived eicosanoid biosynthesis; (2) alteration of metabolism, cell growth and differentiation; (3) alteration of oestrogen metabolism, which leads to reduced oestrogen‐stimulated cell growth; (4) alteration of free radicals and productivity; and (5) alteration of the mechanisms involving insulin sensitivity and membrane fluidity. Interest in the use of supplementary omega‐3‐fatty acids to reduce the risk of cancer and other chronic‐debilitating conditions, including cardiovascular disease and cognitive impairment, stems from several long‐standing avenues of registration [9, 10]. Furthermore, the anticancer activity of fatty acids is well evidenced by Helmut et al. in experimental and human studies, which summarize that a high intake of omega‐3 PUFAs and monounsaturated fatty acids is protective in breast, colon and prostate cancers [11].
Overview of the metabolism of n‐6 and n‐3 polyunsaturated fatty acids (PUFAs) into eicosanoids involved in inflammation and carcinogenesis [12].
The author and her research group isolated methyl gamma linolenate (GLA‐ME) (1) from Spirulina platensis and the compound showed strong cytotoxicity against A‐549 cells [13] when compared with the standard drug Rutin. Rutin is a bioflavanol which is a well‐established promising anticancer agent, and its mechanism may be due to the induction of apoptosis [14]. The comparative results are given in Figure 3 and Table 4, respectively. The probable mechanism may be due to the induction of apoptosis of tumour cells by augmenting free radical generation. It is evidenced by the research work carried out by Unduri et al. [8]. They also reported that the induction of apoptosis of tumour cells by GLA is due to its action at the gene/oncogene level and by altering BCl‐2 expression. Hence, it may be concluded that the cytotoxicity shown by GLA‐ME may be due to the induction of apoptosis effect. However, a detailed study of this mechanism is in progress.
In vitro cytotoxic studies □: GLA‐ME, Δ: standard rutin.
S. no. | Compound | Concentration (µM) | % growth inhibition | CTC50 |
---|---|---|---|---|
1. | GLA‐;ME | 3.333 | 97.45 | 0.468 |
2. | 1.666 | 86.39 | ||
3. | 0.833 | 72.38 | ||
4. | 0.416 | 48.45 | ||
5. | Rutin | 3.333 | 98.65 | 0.442 |
6. | 1.666 | 88.41 | ||
7. | 0.833 | 75.25 | ||
8. | 0.416 | 49.05 |
Determination of cytotoxicity by SRB method.
Kong and co‐workers found out that gamma linolenic acid modulates the response of multidrug‐resistant K562 leukaemic cells to anticancer drugs. The study also revealed that GLA could modulate the response to anticancer drugs in P‐gp overexpressing multidrug‐resistant cells, which could be due to decrease P‐gp expression [15]. In another study, Julie and co‐workers reported that alpha linolenic acid and docosahexaenoic acid alone combined with trastuzumab reduced HER2 overexpressing breast cancer cell growth but differentially regulated HER2‐signalling pathways. Their finding is different in classic mechanisms whereby n‐3 PUFAs exert their effect in breast cancer. The results strongly suggest that DHA reduces growth factor receptor signalling as indicated by reductions in the phosphorylation of AKT and MAPK while the opposite effect is seen for the plant‐based n‐3 PUFA ALA [16]. Effenberger and co‐workers synthesized novel N‐acylhydrazones of doxorubicin which were derived from saturated, unsaturated and methyl or bornyl terminated fatty acids. The mode of cytotoxic action of the hydrazones was largely apoptotic. They led to a distinct long‐term decrease of bcl‐2 MRNA expression, the precise apoptotic mechanism and the involvement of caspases varied for the individual cell lines and test compounds. The apoptosis of 518A2 melanoma cells treated with some compounds was characterized by an early onset of initiator caspase‐9 activity. By contrast, apoptosis elicited in 518A2 or in HL‐60 cells by remaining compounds was accompanied by high‐initiator caspase‐8 activity. The genuine slump of the bcl‐2 mRNA expression may be the reason for the observed quick and steep hike of the ratio of bax mRNA to bcl‐2 mRNA in 518A2 cells. Apoptosis induced by doxorubicin (2) and its derivatives (3) and (4) in HL‐60 and 518A2 cells also proceeds with a swift and distinct loss of mitochondrial membrane potential regardless of the divergent caspase kinetics. This was a proof that fatty acid analogues are more than just lipophilic shuttle groups [17].
Piyali et al. studied the antiproliferative activity of somatostatin analogue with N‐terminal acylation with long‐chain fatty acids in human breast adenocarcinoma cell lines. The antiproliferative activity of the somatostatin analogue RC‐160 (D‐Phe‐Cys‐Tyr‐D‐Trp‐Lys‐Val‐Cys‐Trp‐NH2) is limited by its short serum half‐life. To circumvent this limitation, fatty acids of chain lengths ranging from 4 to 18 were individually conjugated to the N‐terminal residue of RC‐160. Although the affinity of palmitoyl –RC‐160 towards somatostatin receptors remains unaltered when compared to the –RC‐160, it exhibited significantly higher antiproliferative activity on MCF‐7 cells. On further increase in the lipopeptide chain, the bioactivity of lipophilized –RC‐160 was reduced. Increasing the peptide hydrophobicity beyond this range reduced the bioactivity of lipophilized –RC‐160. Accordingly, stearoyl –RC‐160 manifested lower antineoplastic activity and receptor‐binding affinity relative to palmitoyl –RC‐160 and RC‐160 itself. It was observed that an increase in bioactivity was manifested within an optimum range of the lipopeptide. The probable mechanisms may be alterations of the signalling pathways. Lipophilization of RC‐160 with long‐chain fatty acids like palmitic acid improves its stability and antiproliferative activity, thereby improving the scope of enhancing its therapeutic index [18].
A number of investigations have demonstrated that a variety of modified fatty acid analogues are promising molecules in cancer prevention and have potential in the treatment of cancer. Bhupender et al.synthesized fatty acyl amide derivatives of doxorubicin (5) and evaluated their in vitro anticancer activities. The results indicated that the designed molecule with comparable antileukaemia activity to cytarabine with sustained release effect is possible by structure modification [19].
They also synthesized fatty acyl ester derivatives (6) of cytarabine and evaluated them for antileukaemia activity. Some of 2’,5’‐dimyristoyl derivatives of cytarabine were found to inhibit the growth of CCRF‐CEM cells [20]. Liu et al. reported the synthesis and antitumour evaluation of N4 fatty acyl amino derivatives of cytarabine. The bioavailability of cytarabine is low due to its low lipophilicity. In order to improve the lipophilicity and bioavailability of cytarabine, a series of fatty acyl amino acid cytarabine analogues (7) were synthesized. It was found that the derivatives synthesized were more lipophilic than cytarabine. The antitumour activity determined in HL‐600 and HeLa cells showed that the derivatives were more active in HeLa cells than cytarabine while most of them demonstrated similar activity to cytarbine in HL‐60 cells. The length of fatty acids in the derivatives seemed to have an impact on the activity observed [21].
Zhang Chun‐hong and co‐workers synthesized new panaxadiol fatty acid esters (8) and evaluated them for their antitumour activity. Tumour cell used was Vero cell line. Positive control was 5‐FU, blank was an RPMI1640 culture medium, negative control was an RPMI1640 culture medium and the solvent for drugs to be tested. The compounds show the strongest antitumour activity [22].
Earlier, the author of the present chapter has reported some novel fatty acid heterocyclic conjugates and their anticancer evaluation on human lung carcinoma cell lines [23, 24]. The compounds have shown comparable cytotoxicity towards human lung carcinoma cell lines. The compound (9), fatty acid chain substituted 1,3,4‐oxadiazole showed maximum cytotoxic activity. It was observed that the presence of toxophoric –N=C‐O‐ linkage in 1,3,4 oxadiazole nucleus may be responsible for the antitumour activity. Further, 1,3,4 oxadiazole is a good bioisostere of amide and ester functionalities with substantial improvement in biological activity in hydrogen‐bonding interactions with different targets responsible for the tumour development. The 1,2,4‐triazole substituted fatty acid analogues (10) displayed promising cytotoxicity towards human lung carcinoma cell lines. It was also observed that the length of the fatty acids plays a vital role in antitumour activity.
Human fatty acid synthase (HFAS) is a multifunctional enzyme that is essential for the endogenous synthesis of long‐chain fatty acid from its precursor acetyl Co‐A and malonyl Co‐A (Figure 4). Blocking HFAS activity causes cytotoxicity [25]. The unique carboxyl terminal thioesterase (TE) domain of fatty acid chain plays a critical role in regulating the chain length of fatty acid releases. Also, the up‐regulation of HFAS in a variety of cancer makes the thio‐esterase domain a candidate target for therapeutic treatment [26]. It was evident from the literature that the long alkyl/alkenes tail of the fatty acids can bind into the long groove tunnel site of thio‐esterase domain of FAS which may be one of the factors of anticancer activities of fatty acids [27].
Human fatty acid synthase (PDB id: 2PX6).
Employing these strategies, the author and her research group carried out the in silico studies on fatty acid analogues. The group designed new derivatives of stearic acid and palmitic acid and studied their in silico‐binding affinities towards key enzyme human fatty acid synthase‐thio‐esterase domain (PDB code 2PX6). The literature clearly says that an identification of oncogenic antigen‐519 (OA‐519) from human breast carcinoma cells as FAS has made it an important diagnostic and prognostic marker for breast cancer patients [28, 29]. By superposing the scaffold structure of all our designed analogues, it is seen that these analogues bind in the same orientation and similar position in terms of the common structure, that is, long aliphatic chain (Figure 5). It complies with the fact that the substrate‐binding site of HFAS is made up of hydrophobic groove. The docking studies revealed that there are two hydrogen‐bonding interactions between the OH group of triazolo thiadiazole of synthesized analogues and HIS‐2481 and SER‐2308 residues (Figure 6). These interactions revealed the important binding mode, since these two residues are present in the “catalytic triad” of FAS‐TE domain [30]. Further, the long alkyl/alkenyl chain of our synthesized analogues fits into the hydrophobic groove of the substrate‐binding site. The docking pose and hydrogen‐bonding interactions of one of the representative compounds are shown in Figures 5 and 6, respectively.
Docking pose.
Hydrogen‐bonding interactions.
Babak Oskouian and co‐workers reported the overexpression of fatty acid synthase in SKBR3 breast cancer cell line and. The objective of this study was to use a breast cancer‐derived cell line, SKBR3, as a model to define the underlying mechanism for overexpression of FAS in cancer cells [31]. Silva et al. reported a clinic pathological study of ErbB2 and Ki‐67 in head and neck squamous cell carcinoma (SCC) and the overexpression of fatty acid synthase enzyme. They showed FAS expression in HNSCC and pointed out ki‐67 as a useful prognostic marker for these tumours [32]. Michelle Agostini et al. reported the proliferation of human oral squamous carcinoma cells and fatty acid synthase. FAS is overexpressed in several human cancers, such as prostate, breast, bladder, liver, lung, melanoma and oral squamous cell carcinoma [33].
As part of a conclusion to our discussion, the various studies have shown that fatty acids not only augment the tumouricidal action of anticancer drugs but also enhance the uptake of anticancer drugs leading to an increase in the intracellular concentration of the anticancer drugs. The omega‐3 fatty acids have become adjutants to chemotherapeutic agents. Although the production of the above‐said fatty acids is a big challenge, a possibility would be gradually implementing the production of these fatty acids in clinical use. Such novel uses of fatty acids in cancer therapy would provide the lipid field with a new avenue to impact public health.
This chapter describes the historical events related to pesticide use and the pros and cons of pesticide use in Africa. Description for pesticide as any chemical used to prevent, destroy, or repel pests and also the description of pest as any species that interferes with human activities, properties, or health have been provided with examples. In Africa, rapid population growth, illiteracy, food insecurity, weak control systems, and poverty have accelerated the use and misuse of pesticides. Based on the latest, 2018, United Nations estimates the current population of Africa is now estimated at 1.3 billion, that is, 16.6% of the total global population. A large part of African population lives in tropical and subtropical climate with high temperatures [1] and moisture favorable for insects’ population growth, as well as movement, agricultural and animal husbandry activities throughout the year [2]. Through these dynamics, humans modify the components of disease agents, including moisture to promote disease occurrence and spread. Hunger and malnutrition, as a result, are affecting many regions in Africa. In 2016, FAO estimated that 27.4% of the population in Africa is affected by severe food insecurity. Since food insecurity is on the rise, especially in sub-Saharan Africa, the need for increase of food productivity and use of pesticides are unavoidable. Over the past decades, the history of pesticides for agriculture, public health, and construction industry in Africa has gone through milestones with several challenges. These challenges range from limited control in import, distribution, use, storage, and disposal of pesticides. As a result, the risk of exposure and health impact to humans and environment has become another challenge. This chapter not only describes the trend of pesticide use and the negative consequences experienced in the past and the current status but also predicts the future implications for environment and health. Controversies regarding the benefits of pesticide use and the disadvantages that are magnified by lack of knowledge, protection, and malpractice with pesticides are highlighted.
Human activities are a part of struggle for meeting basic needs of life. In order for humans to sustain life, they must discover better means for addressing the development challenges including those relating food security and safety for a peaceful and secure life. In order to sustain productivity, food security, and safety for survival and growth, humans have to control the environmental challenges due to anthropogenic activity including nuisance and threats.
Since before 2000 BC, humans have been utilizing pesticides to protect crops. In Mesopotamia, about 4500 years ago, they used elemental sulfur dusting as pesticide for their crops. In other places, they used poisonous plants for pest control [3]. Other methods of pest control included burning grasses not only to kill insects and to control plant diseases but also to inhibit the growth of unwanted weeds. The serious use of pesticides in the agriculture started in the nineteenth century and expanded in the twentieth century [4]. Pesticides were used to control various pests and disease carriers, such as mosquitoes, fleas, ticks, mice, and rats.
Use of pesticides to control pests of importance in public health and agriculture including animal husbandry and poultry has been necessary for improving health as well as quantity and quality of yield for feeding the growing population. As a result, these pesticides reach the untargeted organisms through direct contact, polluted water sources, air, soil, and the food chain due to weak control systems for importation, supply, use, and disposal. In general, human activities that involve application of pesticides pollute and destroy habitats, untargeted animals, and some plant species. Thus, as unwanted effect, exposure of pests to pesticides leads to pest resistance problem, loss of many untargeted species, and also biological magnification through food chain.
Despite the fact that poorly controlled human activities threaten different untargeted species, agriculture in Africa is threatened by pests, including insects. The insects can either be endemic or epidemic. The endemic insects in Africa include cereal stalk borers that destroy different kinds of cereal crops and crop-eating fall armyworms that destroy a wide variety of crops and also whiteflies that destroy root/tuber crops (e.g., cassava is one of main sources of carbohydrates). Bean flies, aphids, thrips, leafhoppers, whiteflies, and leaf beetles are also among common and endemic insects that destroy legume crops’ source of protein and many more insects in Africa [5].
Epidemic insect attacks in Africa include locust outbreaks (e.g., Madagascar in 1997) that inflicted severe damage to crops and cattle pastures around the country. In this locust outbreak control, fipronil (insecticide) was donated by developed countries, later impact evaluation reported detrimental fipronil effects, ranging from genotoxicity and cytotoxicity, and impaired immune function, to reduced growth and reproductive success of vertebrates, often at concentrations below that which is associated with mortality [6].
Other pests include fungi, virus, and bacteria. There are substantial estimated losses caused by these pests per year. For example, in Tanzania, economic damage due to the other pests on crop productivity is estimated at 50% (Controller and Auditor General established that in 2015).
Human life in Africa is also threatened by vector-borne diseases. Such vectors (pests) transmitting diseases include female anopheles mosquito that transmits Plasmodium falciparum causing malaria. Culex and other mosquito species transmit Wuchereria bancrofti (mostly) causing elephantiasis leading to permanent disability. Fleas harbored by rats transmit Yersinia pestis causing plague and tsetse flies transmit Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense to cause sleeping sickness. Fresh water snails transmit schistosomes causing intestinal and urinary schistosomiasis [7, 8, 9]. All these cause a lot of socioeconomic losses due to diseases and deaths they cause to humans. Other pests like ticks cause health problems to animals.
In order to achieve human and animal health and other social and economic targets, humans need to control pests, so that they can reduce nuisance to increase quantity and quality of crop harvest, the value of harvested crops for sale, and livestock. Not only pest control is necessary for decreasing human and animal diseases and deaths but also for decreasing nuisance, direct destructions of properties as well as promoting peace for social and economic activities to occur.
Pesticides that are mostly used in Africa include insecticides (insects), fungicides (fungi), acaricide (ticks, mites), antibiotics (bacteria), molluscicide (snails), nematicide (nematodes), ovicide (birds), repellents (vectors), rodenticides (rodents), and herbicides (weeds) (Figure 1).
Pesticides and other agrochemicals used in Africa.
Initial history of pesticides is well documented in countries outside Africa. For example, the first generation of pesticides contained naturally occurring metal elements. These inorganic metals included lead, calcium, arsenic, and mercury. These pesticides were mainly discovered and used in European countries and the USA. Later, they were found to be less effective for insect control and they were highly toxic to plants and animals [10]. No data are available on the use of first generation of pesticides in Africa.
Data available for pesticide use in Africa are on second generation of pesticides (organochlorines). Second-generation (synthetic) pesticides were organochlorines such as dichlorodiphenyltrichloroethane (DDT). DDT was first synthesized in 1874 by the young Austrian chemist Othmar Zeidler (as a doctoral student), but in 1939, the DDT’s insecticidal action was first discovered by the Swiss chemist Paul Hermann Müller [11]. These organochlorines replaced inorganic pesticides (first generation). Then, a third generation of pesticides included organophosphates, carbamates, pyrethroids, etc. These are the currently used pesticides in Africa and elsewhere, they were introduced between 1960s and 1980s [12, 13].
In Africa, data on pesticide use [14] are available from when (1939–1960s) the second-generation organochlorines were reported. In Tanzania, DDT was introduced during WWII for malaria and typhus and later, after WWII, it was available for public health and farm vector control. In 1945, DDT was introduced in Monrovia, Liberia, for indoor residual spraying (IRS) for controlling malaria vector [15]. After WWII, there was effective worldwide marketing and from 1950s and after that, there came introduction of lindane, dieldrin, chlordane, and endosulfan. DDT brought happiness to many countries because it was a broad-spectrum pesticide effective at killing pests and could be used by inexperienced people, improved crop yields, and needed no re-application—so, it was a cost-saving pesticide.
During WW II, DDT was applied to control lice (typhus) that caused typhus fever [16], and to control mosquito that caused malaria [17]. Significant decline of malaria transmission and deaths after use of DDT was reported in different African countries from 1940s to 1950s on.
Later, research showed that DDT had a negative effect on the environment and biodiversity. Rachel Carson published the book, namely, Silent Spring in 1962 and the message from this book was an eye opener. She reported that DDT thinned bird egg shells, and, that, eggs were not able to support the weight of incubating birds, so not able to hatch. The reason was that the egg shells lacked enough calcium due to DDT. In addition, DDT had estrogenic effect, thus affecting reproduction. DDT was affecting the nervous system and it also affected immunity leading to failure to resist against infections in animals. So, it was a threat to extinction of birds and other wild creatures [18]. A number of studies have revealed DDT residues in many kinds of samples in several African countries like Nigeria, Tunisia, Ethiopia, Burundi, South Africa, etc., in plants, animal feed, livestock and wild animals, birds including chicken, fish, and humans [19].
In the food chain, plants might have low DDT residues, and they are eaten by chicken, fish, and animals; the DDT concentration levels increase in the tissues, and high up in the chain to reach even innocent newborns via contaminated breast milk (i.e., highest DDT concentration level in the food chain).
As a result, examples of literature about negative effects of DDT in humans in Africa include those in breast milk. Organochlorine pesticides (OCPs) were reported to be present in human breast milk, thus causing health risk to nursing infants in northern Tanzania in 2017 by Müller et al. [20]; in South Africa in 2006 by Bouwman et al. [21]; and also reported in milk and serum of Ghanaian farmers [22]. Furthermore, long-term effects of DDT exposure not only affected semen, fertility, and sexual function of farm workers in South Africa [23], but also caused DDT genotoxicity to cultured lymphocytes in Tunisia [24] and reduced half-life of paracetamol in highly exposed mothers in Zimbabwe [25]. Paracetamol is useful for fever and different kinds of pains in humans, its half-life is 1–3 h (prescription is after minimum of 6 h). Say the half-life is reduced to 30 min due to DDT residues in the body, then, the interval of taking paracetamol must be less than 6 h. Thus, paracetamol toxicity to liver is increased due to increased frequency or it becomes a useless drug in places where DDT is applied.
The negative effects of OCs to the environment and humans outweighed their benefits, leading to ban of OC pesticides; reasons included resistance to degradation in nature and living organisms, its toxicity to biodiversity including humans but also pests developed resistance. So, it was banned in developed countries in 1970s (Europe and the USA).
A worldwide ban on production and use was formalized under the Stockholm Convention on Persistent Organic Pollutants (POPs) signed in 2001 and effected in May 2004. The ban included DDT and other 11 persistent organic pollutants (POPs), namely the dirty dozen. The dirty dozen are characterized by persistence due to slow degradation, they are lipophilic (i.e., high affinity for fatty tissue); so, they accumulate in fatty tissues of living organisms (bioaccumulation), and then there is an increase of concentration in food chain (biomagnification). Due to long (persistence) half-life, they can be transported far from the point of application via air [26]. DDT may be transported from tropical countries to polar regions via evaporation, then, condensed and in summer, again, they can evaporate (grasshopper effect).
DDT is the most effective pesticide for malaria control. Following the ban of the dirty dozen, should DDT be banned for every activity? In 1990, African countries tried to substitute DDT with pyrethroids. The result was the rebound of malaria morbidity and mortality. So, the WHO allowed reintroduction of DDT in 2004. After 2004, mortality decreased. DDT use is reported to have led to decline of malaria morbidity and mortality in Africa. The challenge now for Africa is to rely on DDT use for malaria control despite the negative consequences, including the potential pest resistance.
Figure 2 has been adapted from European Journal TMIH by Musawenkosi et al., 2004. Historical review of malarial control in southern Africa with emphasis on the use of indoor residual house-spraying is given in Figure 3.
Decline of malaria parasite rates in Africa after use of DDT.
Mortality due to malaria in Africa from 1980 to 2016 (90% contribution to global mortality). Figure based on data from UNICEF and WHO.
The organization currently known as African Union launched a program for self-sufficiency in agricultural food production in 1983. It was a 10-year program up to 1993. Example of Tanzania as one of the program implementers in Africa removed restrictions on imports of different pesticides including the banned pesticides; from there, was an observed rapid increase of pesticide imports. In addition to that, there was another increase of pesticide imports from 2000 to 2003 (about 5 times) [27].
On top of increased imports for self-reliance on food production through direct purchase, Africa also received donations from Europe (EU, UK), the USA, Asia (China and India), etc. [28]. Within the country, there are suppliers and distributors, that is registered companies and small-scale traders operating via local shops and also vendors.
As a result of donations and poorly planned imports, many countries in Africa have remained with obsolete pesticides accumulated over the past decades. These persistent organochlorine pesticides were stocked for use, but no longer useful, they required disposal because they have become a source of pollution to the environment and food chain and direct threat to human health.
Organochlorine pesticides were banned in developed countries in 1970s. At that time, many African countries received large donations of DDT and malathion for malaria control programs. Additional description was that the donations were for preparedness against locust outbreaks. This was an act of disposal and smart donation to solve environmental problems in donor countries. In addition, in 1991, during implementation of self-reliance program on food production, 1900 tons of banned pesticides manufactured in the USA were shipped to Africa. In some cases, there were even excessive donations without examining the actual need for these products in the recipient country. There were no prior arrangements for distribution and storage of these pesticides.
This was reported in Pesticides and agrochemical industry in sub-Saharan Africa, July 1994 (Contractual work prepared for division of food, agriculture and resource analysis-office of analysis, research and technical support bureau for Africa).
Despite the cleanup program, there are still high levels of DDT and HCHs that were found in soil and water around. Although the visible remains of pesticides were removed, the soil is itself hazardous waste. For example, in Vikuge, in Tanzania, concentrations of DDT in grasses from nearby Vikuge were far above the acceptable limits for animal feed. Even at 6-km distance from Vikuge, DDT concentrations in grasses (animal feed) were still two times higher than the acceptable limits [29].
Other areas under the same cleanup program in 2013–2015 included Mali, Ethiopia, Morocco, Tunisia, and South Africa. Example of operations in Tanzania identified 14 sites of obsolete stockpiles. Three hundred tons of DDT of contaminated soils in Morogoro Region (one of the regions in Tanzania) were collected for destruction and 200 tons of DDT collected from the government-owned livestock farm at Vikuge [30].
Recent findings of pesticides (2016) in chicken eggs from Arusha, in Tanzania, by Polder et al. report that there are POPs including pesticides from free-ranging chicken eggs (free-ranging chicken are common in Africa for family use and for sale). They collect food from soil around the homes and come back during sunset. These findings from Arusha revealed extremely high levels of dieldrin in eggs from one specific urban farmer. This finding may reflect a possible source from an obsolete stockpile that was situated on that site before the town expanded.
Third generation of pesticides came in between 1960s and 1980s: these included organophosphates, carbamates, etc. These are the rapidly degraded pesticides, so they are less persistent in environment. They are acutely toxic to pests and more lethal in low dose compared to the banned organochlorines. The current global consumption of pesticides is at 2 million tons per year; of these, 25% (500,000 tons) is consumed in developing countries and 4% (80,000 tons) of global consumption is from Africa [31].
A survey report named Pesticides and Poverty [28] showed a number of problems noted in Africa; these include weak government organs for pesticide control systems, in particular, planning imports (imports may be in excess of requirements, so there is lack of efficiency). There are also weaknesses in supply and distribution (farmers accessed late and sometimes not according to needs). There is poor control (illegal entry of 2% pesticides, loop holes for misuse) and poor disposal plans of the remains. There is illegal trading (unwanted pesticides including WHO class I and unknown ingredients).
There are problems by users. These include not only improper practices (no personal protective equipment, contaminated water sources during pesticide applications) but also improper storage and disposal (throwing and burying containers in fields). In addition, users have low knowledge (on safe use and the associated health risks, also users cannot diagnose the plant disease and prescribe accurately), skills, and capacity. Some pesticide users have never attended formal education in school, these are the majority of that improperly use, store and dispose the pesticides.
Common human exposure is through spraying (including mixing and loading), weeding, pruning, harvesting, etc., but also drift near the areas of pesticide applications, indoor spaying of mosquitoes, cockroaches, flies, ants, etc. Direct contact with contaminated materials (at farm/home) and ingestion (poor hygiene) are common exposure pathways.
African countries are taking some steps to address the described problems, these steps include the following: African member states have ratified the UN pesticide conventions and protocols as described by Flaubert Nana Sani (AU-IAPSC). Most African member states at the moment have Pesticide Evaluation Report & Safer Use Action Plans. At the moment, there are subregional regulatory bodies in Africa, these include: Central Africa Inter-State Pesticides Committee, the South East Africa Regulatory Committee on Harmonization, and another one for the west African member states. Among the activities that have been done by these member states at different levels include establishing harmonized pesticide registration, procedures, and evaluation criteria.
Pesticides are important for economic development, food security (enough food, to avoid hunger), food production (able to conduct agricultural activities for food availability without pest disturbance), food safety (preventing biological harm to consumers), food quality (nutrients, appearance, texture, flavor, chemical, physical, microbial properties, etc.), vector disease control, improving human and animal health, decreasing morbidities and mortalities, insect nuisance control, and increased life quality. All these lead to peace.
Not only have controlled vector-related diseases (acute and chronic) including malaria morbidity and mortality been significantly reduced but also threat of elephantiasis and bilharziasis has gone down among many pest and vector-borne/related diseases. The same controlled picture is observed in animal health and zoonotic diseases.
Pesticides contaminate water, air, and soil, leading to damage of ecosystems (some organisms and habitats are destroyed and no longer exist in their natural habitat). Thus, pesticides diminish biodiversity (some biological species become extinct) and affect natural biological equilibrium. In affected systems of living organisms, some biological species are forced to live in new environment; thus, they adapt and may become pests. Some pests prevail in excess or less where not expected.
Other problems due to pesticides include pesticide resistance and costs to controlling resistance. Human and animal exposure to pesticides end into health problems and also it is reported that efficacy of the vaccine is reduced due to exposure to pesticides. Pesticides are threats to human health by directly causing diseases. Diseases due to pesticides can be divided into two kinds of manifestations: acute and chronic poisoning.
In acute poisoning (high dose), the body reacts to present with diarrhea, vomiting, coughing, difficult breathing, skin irritation, rashes, fasciculation, headache, dizziness, etc. When humans are exposed to low dose, chronic symptoms manifest including slow onset of symptoms. Pesticides are neurotoxicants, so they affect the central nervous system and manifest through loss of memory, orientation to time and space, etc., and on the peripheral nervous system, numbness of feet and hands manifest among other symptoms. Pesticides also have effects on reproductive system because they are endocrine disruptors (they affect reproduction, e.g., lead to abortions, etc.). On immune system, they disturb body function, so resistance to infections is reduced. Cancers, for example, lymphomas, sarcoma, etc., are also reported to occur more in populations exposed to pesticides (cause effect not established). In addition, more than 40% of the health care professionals interviewed could not recognize pesticide poisoning cases; this reflects that the recognition for chronic manifestation of low-dose occupational exposure to pesticides may be worse [14].
Contamination of water threatens aquatic organisms, frogs, and fish, leading to extinction of aquatic biodiversity. Contamination of soil may lead to extinction of fertilizing organisms, whereas air pollution leads to population decline of pollinators (honey bees). The persistent organic pollutants are transported far away from the area of application and they end up in biomagnification that threatens human health.
In addition, environmental contamination causes lack of safe water supply for human consumption, which threatens human health. Contaminated water and grass lead to wildlife poisoning and extinction of wildlife including birds, leading to loss of small mammals, bird species, and insects.
Pesticides are expensive. Since pesticide use is a solution for temporary protection, it forces frequent use that in turn increases risk of exposures. As a result, pesticide resistance occurs. Pest resistance is a big challenge. When the pests do not die following pesticide application, the users increase the dose. At the same time, the natural enemies for pests are killed by pesticides during applications, leading to pest resurgence. Pests come back stronger than before because there is no natural enemy. To control pest resurgence, the users increase quantity and frequency for spraying. As a result, secondary pest outbreak occurs, in which, normal species become pests because natural enemy is destroyed. This kind of new pest is sprayed like target pest.
Human struggle for survival has led to increased use of pesticides. Loopholes in controlling use and disposal of pesticides have threatened the human and environment health over decades. As a result, morbidities and mortalities and other negative consequences to untargeted biological organisms need serious considerations and adequate actions. Recommendations may not be limited to adjustment of the laws and regulations to be in harmony with international conventions and standards but also strengthening implementation and enforcement of the existing rules and regulations, registration and quality controls. Having infrastructure for handling sewage systems and proper disposal systems for pesticides and other chemicals and development of alternative for sustainable food production is important. Education and training on safe pesticide use, storage, disposition of pesticides and training in schools on environmental, occupational and dietary-related non-communicable diseases are necessary.
The following colleagues from Norwegian University of Life Sciences, Oslo, are sincerely acknowledged for their professional contributions that went into this piece of work. Prof Jan Ludvig Lyche (PhD) is acknowledged for critical reading and comments on the content. Dr. Anuschka Polder (PhD) is acknowledged for contribution on the flow of arguments during writing process. Dr. Mette Hellen Bjorge Müller (PhD) is acknowledged for constructive advices and comments.
It is declared that there is no conflict of interest between the author and any other part regarding the content of this chapter.
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