**5. Toxicology of pesticides**

 Widespread use of pesticides is a significant source of air, water, and soil pollution causing risk to human health as a result of misuse or accident as well as leaving lasting harmful chemicals in the environment [63]. Also, effects of agricultural pesticides on nontarget organisms continue to become a major problem. Indiscriminate and injudicious use of chemical pesticide in agriculture has resulted in several associated adverse effects as environmental pollution, ecological imbalance, and pesticide residues in food, fruit, vegetable, fodder, soil, and water pest resurgence [64].

The WHO [46] grouped pesticides according to the potential risks to humans caused by accidental contact to human being to five classes:

Class Ia. Extremely dangerous parathion, dieldrin.

Class Ib. Highly dangerous eldrin, dichlorvos.

Class II. Moderately hazardous DDT, chlordane.

Class III. Slightly hazardous malathion.

Class IV. Products unlikely to present acute hazard in normal use.

The majority of pesticides are not specifically targeting the pest, during the application nontarget plants and animals are also affected, only about 0.1% pesticides reach the target organism, and the remaining applied pesticides contaminate the surrounding environment [63, 65].

Toxicity can be either acute or chronic:


*Pesticides, Anthropogenic Activities, and the Health of Our Environment Safety DOI: http://dx.doi.org/10.5772/intechopen.84161* 

#### **5.1 Effects on humans**

The main purpose of IPM is to reduce the effects of pests on crop product and help meet the increasing demand of larger population around the world. Although the application of pesticides achieves the goals of its usage, but at the same time, side effects also appear because of this practice.

Application of pesticides is a major threat to human health. It can taint food, water, soil, and air, causing headaches, drowsiness, fertility issues, and life-threatening illness; hundreds of thousands of known deaths occur each year due to pesticide poisoning [67]. Pesticide use has contributed toward improving agricultural production, in both yield and quality. Pesticides are also widely used in a variety of other settings, some of which most of the general public are not aware of [68]. It is evident that workers who are involved in mixing, loading, transport, and application of pesticide are at the highest risk of pesticide injury [69]. Pesticides can enter into the human body in three ways: (a) through the mouth (oral administration), (b) by adsorption through the skin or eyes (dermal adsorption), and (c) by breathing (inhalation) [70].

Also, atmospheric pesticides can cause hazards to humans. Atmospheric movement may cause transportation of pesticides from application sites to sensitive areas and accumulation of pesticides in the environment [71].

Risk related to pesticide poisoning can be defined as the extent of getting exposed to pesticide with a certain degree of toxicity. These can be expressed as Risk = Toxicity × Exposure [70].

#### *5.1.1 Organochlorine pesticides (OCPs)*

Organochlorine pesticides (OCPs) show multiple effects on the major physiological systems of the body including nervous, circulatory, and reproductive system and, also at some critical growth periods, may generate severe health disturbances [72].

Organophosphorus compounds are commonly used as insecticides. Organophosphate inhibits AChE, an enzyme located in the postsynaptic membrane that degrades AChE into choline and acetic acid [73]. The enzyme is classified as a B esterase whose function is the hydrolysis of acetylcholine which is a major neurotransmitter in the peripheral and central nervous system. The inhibition disturbs the capability of the enzyme to bind to its normal substrate with the subsequent accumulation of AChE at the nerve ending [74, 75]. The systematic investigation of the relationship between chemical structure and inhibition of AChE is the single most important feature required in an organophosphate for anticholinesterase activity and chemical reactivity; it has revealed a direct relationship between anticholinesterase activity and reactivity of the phosphorus atom [76]. Also, OPs can cause a type of toxicity called organophosphate-induced delayed polyneuropathy (OPIDP). It is characterized by deterioration of the long axons in the central and peripheral nervous system and ends with ataxia and paralysis which appear about 2–3 weeks after exposure [74]. Another side effect of Ops is oxidative stress and apoptosis. The damage is generated by the imbalance between reactive oxygen species (ROS) production and elimination [77]. Another side effect of Ops on human health is the disruption of estrogen function by acting as a ligand for receptor, converting other steroids to active estrogen or increasing the expression of estrogen-responsive genes [78]. Other Ops are capable of interfering with the endocrine function by inhibiting the binding of thyroid hormones to their corresponding receptors [78, 79]. Reiss [80] found out that the critical exposure period to PO insecticides for human neurological development is, by definition, the only relevant exposure for birth outcomes. Naksen et al. [81] reported that the birth outcomes as a result of OP exposure suggest a decrease in birth weight and head circumference in newborns born from mothers with low PONI activity.

#### *5.1.2 Carbamates*

Carbamates are hepatically metabolized via hydrolysis, hydroxylation, and conjugation, and 90% is renally excreted in a matter of days. The data of carbamates on central nervous system (CNS) and cerebrospinal fluid penetration, adults tend to have less CNS toxicity, whereas, in pediatric exposures, CNS depression is often a predominant symptom. Carbamates do not undergo aging that occurs during the phosphorylation of organophosphate to acetylcholinesterase and the carbamate-cholinesterase hydrolysis spontaneously within hours [82]. Fukuto [76] found out that insecticide carbamate causes AChE inhibition by identical mechanism to that of Ops. Unlike Ops poisoning, carbamate poisoning tends to be of shorter duration because the inhibition of nervous tissue acetylcholinesterase is reversible, and carbamates are more rapidly metabolism [83]. Forde [84] studied the effects of pregnant women exposure to carbamate; the results appear to show that carbamate when associated with other pesticides is typically used as OPs and pyrethroids. The result obtained is often related to OPs and pyrethroids. Carbamates are usually considered to be of limited acute toxicity.

#### *5.1.3 Pyrethroids*

 The toxic effects of pyrethroids include neurotoxicity, skin contact, and respiratory and reproductive system toxicities [77]. Type I pyrethroid typical effects include rapid onset of aggressive behavior and increased sensitivity to external stimuli, followed by fine tremor, prostration with coarse whole-body tremor, elevated body temperature, coma, and death [85]. Type II pyrethroid effects are typically characterized by pawing and burrowing behaviors, followed by profuse salivation, increased startled response, abnormal hindlimb movement, and coarse whole-body tremors that progress to sinuous writhing. Clonic seizures may be observed prior to death; the term CS-syndrome (from choreoathetosis and salivation) has been applied to type II responses [85]. Gliga et al. [86] assessed the effects of three major herbicides, three insecticides, and three fungicides on three human cell lines (HepG2, HEK294, and JEG3); they found that fungicides were the most toxic from concentration 300–600 times lower than agricultural dilution, followed by herbicides and then insecticides, with very similar profiles in all cell types. LEG3 was the most sensitive cell line.

Nonoccupational low-dose exposure of any pesticides causes chronic disease in humans and can be considered as a silent killer; almost every crop faces a number of applications of different pesticides which results into multi-residue exposure of these pesticides that could be more in causing toxicity effects [87].

#### **5.2 Effects on plants**

Plants are the primary source of food for humans through crop production; crop safety and crop productivity are of paramount importance to ensure providing sufficient and healthy food for peoples.

Plants were the main reasons for pesticide application and practices, but in the early days of chemical pesticide applications, there were little concern about the side effects of this practice until illness started to appear on farmers and farm workers who are directly exposed to pesticides and using crop products that are treated with chemical pesticides. These effects alarmed governments, agriculture intuitions, and scientists around the world to pay a greater attention to these chemical pesticides used for crop protections.

*Pesticides, Anthropogenic Activities, and the Health of Our Environment Safety DOI: http://dx.doi.org/10.5772/intechopen.84161* 

Anonymous [88] found that absorption is the take-in of chemical substance into plants or microorganism. Most chemical pesticides break down once they are absorbed; pesticide residues may separate into simpler substances or remain inside the plant or animals and be released into the environment when the animal dies or plant decays.

A result of the study of Nishisaka et al. [89] to assess the genotoxicity effect of nanoparticles containing the paraquat herbicide indicated less chromosome damage than conventional paraquat herbicide. Saha and Gupta [90] found out that metallic nanoparticle, e.g., Ag NPs, causes significant toxic effects in animal cell culture and animal models; the impact of (Ag NPs) on plant species is related to oxidative stress-related gene expression, genotoxicity, seed germination, and root elongation; and genotoxic city studies revealed different types of chromosomal abnormalities and DNA damages which ultimately lead to cell death and disintegration of plant cell exposed to different coated and uncoated Ag NPs present in the environment. Toxicity of nanoparticles depends upon various factors like plant species, size, and concentration of nanoparticles in different stages of crops; it also depends on their composition and size. Small-sized nanoparticles are more reactive and toxic than the large-sized ones and affect the respiration or photosynthesis process [91]. For example, AL2O3 NPs showed phytotoxicity only on corn, reducing the root elongation by 35%. All improved root growth of grape and radish and inhibited root elongation of ryegrass and lettuce but had no effect on cucumber [92]. Boonyanitipong et al. [93] assess the effect of ZnO NPs on rice plant; the result shows adverse effect on rice from 100 mg/L and fully inhabit root growth and biomass at 500–1000 mg/L concentration. In a study of the effect of TiO2 nanoparticle on aquatic life, the result raveled that TiO2 reduced the light to entrap the algal cell and thus reduce the growth [94].

#### **5.3 Effects on environment**

 The Environment Protection Act (EPA) (1986) defined the term environment under Section 2(a) of "to include water, air, land and inter-relationship between water, air, land and human being, other living creatures, plants, microorganisms and property." The definition includes complex relationship between environment parts; these parts must be in balance to insure healthy and accurate relationship.

Any disturbance in these relationships may lead to undesirable result. One of the most effected factors that play great roll in this disturbance is the application of different types of pesticides.

 The potential for misapplication and accidental exposure is great [64]. It is found that only a very small part of the total amount of pesticides applied for weed and pest control (<0.1%) actually reaches the sites of action [95]. The runoff from agriculture and urban land, and rain precipitation and dry disposition from the atmosphere, can transport pesticides to streams and groundwater [96]. Mahmood et al. [97] reported that excessive use of pesticides may lead to the destruction of biodiversity. Birds, aquatic organism, and animals are under the threat of harmful pesticides. The soil is an important part of the environment and plays an effective role in other parts. The application of pesticides results into two ways: positive way by destroying the specific target and negative way by transferring to another nonspecific target. In a study of Cessna et al. [98], they found that pesticides enter to the atmosphere by application drift, post-application vapor losses, or wind erosion of pesticide-treated soil; also, their photodegradation may be transported in long distances before the removal processes of atmospheric wet and dry deposition return them to the earth surface. Pesticides that were detected in the atmosphere are (I) organochlorine insecticides (resistant to environmental degradation), (II) organophosphate insecticides (not long lived in the environment), (III) atrazine herbicides (heavily used herbicides, persistent in the environment), (IV) acetanilide herbicides

 (used heavily, but not as persistent as atrazine) [71]. Mobility may result in redistribution within the application site and sometimes off-site. After application, a pesticide may (I) attach to soil particles, vegetation, or other surfaces and remain near the site; (II) attach to soil particles and move with eroded soil in runoff or wind; (III) dissolve in water and be absorbed by plants, overflow, or leach; (IV) pass off in vapor or erode from foliage or soil with wind and become airborne [99]. Also, the mobility of pesticides can be affected by several factors of pesticide sorption, water solubility, vapor pressure, and other environmental and site characteristics including weather, topography, canopy, ground cover, soil organic matter, texture, and structure [99]. The persistence of pesticide is expressed in terms of half-life that can help estimate whether or not a pesticide tends to build up in the environment. Pesticide half-lives are classified into three groups: low (less than 16-day half-life), moderate (16–59 days), and high (over 60 days). Pesticides with shorter half-lives tend to build up less and less likely to persist in the environment, while pesticides with longer half-lives are more likely to build up after repeated application. Higher persistence increases the risk of contamination of nearby surface water, groundwater, plants, and animals. Anonymous [88] reported that some pesticides stay in the soil long enough to be absorbed by plants grown in the field years later. The behavior of pesticides in soil is governed by a variety of complex dynamic physical, chemical, and biological processes, including sorption-desorption, volatilization, chemical and biological degradation, uptake by plants, runoff, and leaching [100, 101].

Biopesticides have benefits and limitation effects on the environment, human life, or agricultural product. They are highly effective in managing pests and diseases, without creating negative impacts on the environment, and their active and inert ingredients are generally recognized as safe. Besides the microbial content, carrier media for formulating biopesticide were consisted of several organic materials, such as animal broth, organic materials, or organic waste product. The media is a biodegradable material. In addition, biopesticides support stability and sustainability of agroecosystem because they did not affect negatively on the environment [102].

 The nanoagrochemical is crucial to modern agriculture, and due to their direct and intentional application in the environment, nanoagrochemical may be regarded as particularly critical in terms of possible environmental impact, as they would represent the only intentional diffuse source of engineered nanoparticles in the environment [103]. There is harmful chemical reaction and contamination by nanoparticles to soil ecosystem and change in soil structure due to their large surface area and Brownian motion [45]. Kah et al. [104] assess the environmental fate of nanopesticides; the result suggests that the photodegradation and sorption behavior of clothianidin may have a greater impact on the environmental fate of pesticide AI than commercial formulations. AI clothianidin was rapidly released from the nanocarrier systems and that the durability of three nanoformulations would be short in water as well as in soil. Nanoparticles can easily be released in the water body or air, and uptake by living organisms creates toxic effect for humans and animals [43]. Bai et al. [105] found that CU nanoparticles caused damage in the central nervous system. Gliga et al. [86] study the effects of Ag nanoparticles, and the results show that Ag particles of size 10 nm were found more cytotoxic than other sizes.

#### **6. The future**

Pesticides are essential to improve the production of crops. The quantity of pesticides will continue to increase as long as the use of pesticides increases. Despite the tremendous benefits of pesticides for human beings especially in agriculture fields, side effects and undesirable results of pest managements such as pesticide residue

#### *Pesticides, Anthropogenic Activities, and the Health of Our Environment Safety DOI: http://dx.doi.org/10.5772/intechopen.84161*

 crop products that are used in feed lead to several human illnesses in soil and water, microflora in soil, and ecosystem in general. Not until the year 1962 when biologist Carson published her book *Silent Spring* when dichlorodiphenyltrichloroethane (DDT) was at its high production 82 million Kg/year in the United States, it was initially used with great effect to combat malaria, typhus, and the other insect-borne human diseases among both military and civilian populations. The book inspired public concern about the toxicity in wildlife, contamination, and the increasing pest resistance. Control of regulated or quarantined pests is typically done through prevention of entry to a country or an area, eradication and containment, and use of tools such as biological control, pesticides and biopesticides, plant resistance, cultural methods, and natural enemy encouragement. In 2016 a review suggested that classical biological control has provided and should continue to provide many positive outcomes for dealing with damaging invasive alien insect pests [106].

Genetically modified (GM) food is a new type of potentially safer food without the use of pesticides; crops producing pesticides substance from genetic material that has been added to the plant. To insure safety, the EFSA Panel on Genetically Modified Organisms (GMO) require scientific risk assessment on the possible risk they might present for humans, animal health, and the environment before being authorized for market placement [107]. Also, the OECD Working Group for the Safety of Novel Foods and Feeds (WG-SNFF) addresses aspects of the safety assessment of food and feeds derived from genetically engineered crops. Their primary aim is promoting the use of consistent methods and data elements used in the risk/ safety assessments among countries. The approach is to compare transgenic crops and derived products with similar conventional ones that are already known and considered safe for use, based on recognized practices, harmonized methods, and data sharing facilitated through the WG-SNFF [108].

 Maximizing pesticide efficiency requires the use of radiolabeled pesticides to study pesticide metabolism, fate, residues, and formulation [109]. An increasing number of countries started to develop control strategies for the use of pesticides. The Danish National Action Plans on pesticide (2017–2021) strategy were (1) authorization of pesticides, (2) targeted inspection efforts, (3) collection of knowledge via the pesticide research program, and (4) information, advice, and guidance.

 The Report of the OECD Workshop on Sustainable Pest Management in Practice: Anticipating and Adapting to Changes in the Pesticides Regulatory Landscape status and subsequent availability of agricultural pesticide products are necessary for sustainable pest management, including the use of registered agricultural pesticides. In general, the consequences of regulatory decision and the entailing process of adaptation of the agricultural production are not widely considered within the registration process. Regulators, pesticide manufactures, and pesticide users in OECD member countries have had to adapt their practices to ensure that sustainable and effective pest management options remain possible. These changes reduce risk to human health and the environment while promoting sustainable agriculture [110]. The Secretariat 2017 [111] in their 34 sessions includes recommendation that:


While pesticides proved effective in mitigation of harmful bugs, the risk associated with their use has exceeded their beneficial effects. Nonselective pesticides can harm nontarget plants and animals along with the targeted ones; also with repeated use, some pests develop genetic resistance to pesticides [97].

 To control the use of pesticides and reduce their effects, registration is an important aspect of pesticide management to ensure that the pesticide products released in the market are authorized and used only for their planned purpose. It will also enable authorities to implement controls for the price, packaging, labeling, safety, and advertisement of pesticides to ascertain protection of the user's interests [112].

To reduce pesticide impact on the environment, minimize contamination, and ensure the safety of human sources of food and water (surface and groundwater), users should be:


 Biopesticides have attracted attention in pest management in recent decades and have long promoted as prospective alternative to synthetic pesticides [68]. Although biopesticide use at a global scale is increasing by almost 10% every year [114], the global market must increase further in the future if these pesticides are to play a visible role in substituting for chemical pesticides and reducing the current overreliance on them [115]. It is expected that biopesticides will equalize with synthetics in terms of market size, between the late 2040s and the early 2050s [116]. Also, Soesanto [101] The conclusion of biopesticides was that biopesticides are the best way to control plant pathogens because of their beneficial effects; though there are still many limitations to be reduced, biopesticides supported stability and sustainability of agroecosystem because they did affect negatively on the environment.

Nanotechnology is the new type of IPM providing a promising future in the direction of formulation that can be used to improve the stability and effectiveness of natural product [117, 118]; it provides controlled release of the molecules at the site of action, can minimize potential toxic effects on nontarget organisms, and can prevent degradation of the active agent by microorganisms [118, 119]. Nanotechnology that includes nanopesticides seems to have a promising future in IPM. The potential toxicity of these nanoparticles is not standardized and not well understood yet explored by international and national safety regulators [60, 120–122]. Athanassious et al. [60] report that safer nanopesticides as alternative methods and practice should take the following into consideration: (a) The process of nanomaterial synthesis may cause changes in dimensions and shape; therefore, risk assessment studies are essential before the use of such materials. (b) Specific guidelines explain how to use these formulations on nanomaterials. (c) The toxic nature of these compounds to plants and insects needs to be analyzed.

*Pesticides, Anthropogenic Activities, and the Health of Our Environment Safety DOI: http://dx.doi.org/10.5772/intechopen.84161* 

(d) Working on nanopesticide formulation before they become more popular in pest management by combining analytical techniques that can detect, characterize, and quantify the active ingredient and adjuvants emanating from the formulation.

Emerging pesticide nanoformulations are not only increasingly complex and biologically active but may also exhibit a potential change in the physicochemical properties and/or biological effects at a size range that is larger than the nanoscale (>100 nm) [30].


## **7. Conclusion**

Continuous growth in population around the world leads to increase the demand for higher crop production. The quality and quantity of crops provided to people must be satisfactory, which can be achieved by using specific methods to control pests that play a great role in crop losses and poor product. The main method used for this purpose is synthetic pesticides, with other methods: biopesticides and nanopesticides. Despite the harmful side effects especially of synthetic pesticide compared to the other methods with less harmful effects on humans, plants, and the environment, still the synthetic pesticides play an important part of IPM. This requires intensive work of scientists, institutions of agriculture around the world, environment studies to assess and evaluate the side effects of these different methods, and provide good training for safer application of pesticides and also continues studies for every new chemical production and methods used in the agriculture field, to decrease and minimize the harmful effects on humans, animals, plants, nontarget organisms, and the environment, including aquatic environment.

### **Conflict of interest**

The author declares no conflict of interest.

#### **Author details**

Mona Saud AL-Ahmadi Department of Biology, Science College, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia

\*Address all correspondence to: dr.alahmdi2009@yahoo.com

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
