**5. Effect of pesticides on health and the environment**

The importance of agricultural pesticides for developing countries is undeniable. However, the issue of human health and environmental risks has emerged as a key problem for these countries in a number of studies [107–112]. Attention to the impacts of pesticide use on the environment and ecosystems has grown since the book *Silent Spring* was published in 1962. Extensive published literature has well documented the impacts of pesticide use to the ecosystem and human health [55]. Pesticides can move off-site to contaminate surface water and leach to groundwater. Damage to nontarget organisms and pollution to the soil and air are well documented [59].

The released pesticides into the environment and their impacts on many species have been known for a long time. The senseless and widespread use of OCPs between the 1960s and the 1970s caused a striking decrease in wildlife populations nearly all over the world [113]. DDT, dieldrin, and other toxic OCPs affected birds and other wild species during that time and have been finally banned from agricultural use. Since then, however, decline in birds, wild bees, and aquatic organism populations have been continuing [114]. This could be linked to usages of newly synthesized pesticides that are present in every kind of habitat on the world. Pesticides are still being discovered in marine, freshwater, and terrestrial communities [115].

Insecticides may kill not only the target species but also other invertebrates on which birds rely on for their food. In addition, herbicides are designed to control weed species and they can also kill many other plant species in fields, including the essentially beneficial species, which give both shelter and food for the members of wildlife. Amphibians are now considered the most threatened and rapidly decreasing species on Earth. Brühl et al. [116] suggested that frogs are sensitive to the toxicity of pesticides that are currently used in agriculture.

In addition, pesticide factory workers and agricultural farm workers have high risk to pesticide direct exposures [88]. In recent years, pesticide residues in food have become a focus for food safety and trade. Quarantine regulations sometimes require pesticide treatment of food shipments to prevent the establishment of exotic pests. Nonetheless, local consumers and international trading partners increasingly demand food that is free from unsafe pesticide residues. Therefore, many countries have initiated programs to monitor pesticide residues in food. In addition, many countries are implementing programs to reduce the use of pesticides and thereby minimize pesticide impacts [59].

Intensively used pesticides, despite their ability to protect crops, threaten the environment and human health [88,117]. Besides, the use of pesticides also results in residue problems. Pesticide residue is defined by the WHO as any substance or mixture of substances in the food of either humans or animals that is caused by the use of pesticides and any specified derivatives, such as degradation and conversion products, reaction products, metabolites, and impurities that are considered toxic [118].

#### **5.1. How are we exposed to pesticides?**

People who live in agricultural areas have a high disclosure to pesticides by inhalation of pesticide spray blow in urban areas and parks or in the houses after breathing contaminated air. Farmers and their families can have a higher exposure to pesticides than the general population. Besides, when nursing mothers and pregnant women are exposed to pesticides, their children may also be exposed. Some pesticides can pass through the placenta to the developing fetus in the womb and through breast milk to the nursing infant [119].

These "poisons by design" are prevalent and serious occupational hazards faced by farmers and agricultural workers [117]. The high levels of occupational exposure to pesticides are correlated with low educational levels, which would preclude the ability of farmers to follow the hazard warnings developed by the chemical industries and agencies [120]. Tragedies, such as acute and chronic intoxication and, in some extreme cases, suicide, have frequently been reported, especially in rural regions [117,121]. The lack of a legislative framework regulating the use of pesticides also contributes to the high incidence of poisoning in developing countries [117].

The present data seem to be too limited to analyze the full health effects of pesticide referable chronic exposures. On the contrary, suicide commitments in 2002 using pesticides resulted in 258,000 deaths [122]. In 2002, intentional poisoning from pesticides accounted for approxi‐ mately one third of the world's suicides, and in 2004, 71% of the unintentional poisonings were considered preventable by improving chemical safety methods [45]. The groups most at risk from unintentional pesticide poisoning are children, especially those between ages 0 and 4 years [123]. Human deaths induced by insecticides were mainly because of ingestion of OPPs. OPP poisoning is evident for "cholinergic syndrome". The symptoms in this syndrome are headache, slurred speech, coma, blurred vision, convulsions, blockage of the respiratory center, and delayed neuropathy [124]. In this sense, survivors of acute OPP poisoning may suffer long-term adverse effects to the nervous system [119].

Data show that there is a positive relationship between high pesticide exposures and occur‐ rence of several types of cancer (e.g. prostate and lung) as well as the increase of neurodege‐ nerative diseases, such as Alzheimer's and Parkinson's disease. There are also evidences that pesticides may impair endocrine function and the immune system. Although the mechanisms of such failures are not completely comprehended, there are some clear evidences showing the disruptions in enzymatic function and signaling mechanisms at cellular levels. DNA-based toxicity studies also indicate that pesticides affect gene expression and this may transferred to generations through epigenetic inheritance [119].

Organophosphate compounds (OCs) and OCPs have been widely used as pesticides in agricultural productivity. However, they have been proven to be extremely hazardous for human health. OCs and other pesticides may persist on Earth for a long time, adverse to the ecology. Therefore, pesticide residues in vegetables, fruits, water, and on Earth are drawing more and more attention [125–128]. Applied pesticide residues may persist within the tissues or on the surface of the crops when we buy from market. Scientists have developed a variety of techniques to both determine and quantify the pesticide levels in food. Data obtained from these studies suggested that nonstop monitoring is needed to ensure that pesticide residues do not exceed their acceptable values [99]. Most countries, on either a regional or a national basis, maintain a threshold maximum residue level (MRL) for each substance, above which the foodstuff is thought unacceptable for human consumption [119].

OCPs are among the substances restricted or banned globally under the Stockholm Convention on Persistent Organic Pollutants [129]. These compounds are environmentally persistent [130], toxic, and apt to bioaccumulation [131] and have adverse effects on animals and humans [132]. Some developing countries are still using these compounds because of their low cost and versatility in industry, agriculture, and public health [133]. Consequently, environmental problems associated with toxic contamination in these countries are of great concern [134]. As a result, organochlorines in various environmental media have received much attention [133]. They are well-known anthropogenic and lipophilic pollutants due to their high bioaccumula‐ tion potential in fatty tissues of living organisms [135]. Although these substances are generally stored in the fat and muscles of the animals, some can also be found in the brain, lungs, liver, and other offal. Additionally, because milk and other dairy products contain a range of fat, these foods may also contain a number of pesticides. This is important because cow's milk is one of the indispensable components of human diet [119,136,137]. OCPs can enter animal tissues through different pathways of ingestion, dermal contact of dust, and inhalation [138].

In the past decades, attention was focused on the determination and pollution levels of OCPs in human blood serum, maternal and cord serum, adipose tissue, human milk, and hair and other available tissues to study human exposure and assess health risk [139]. Human exposure to OCPs is through many routes: breathing OCP-contaminated air, working in or living beside OCP factories, drinking and taking a bath with OCP-polluted source water, eating vegetables and grains containing OCP residues, and eating especially fish and animal meats [140]. OCPs accumulated in the human body could cause various negative effects such as immunological function damage, endocrine disruption, female spontaneous abortions and preterm, and children neurodevelopmental delays [141].

Several studies showed that cancer risks could be induced by OCP exposures [142]. At the same time, OCPs could be transferred from maternal to fetal tissues through placenta and from mother to infant through breast milk. Exposure to OCPs could also lead to some adverse effects on human productivity, including spontaneous abortions and preterm [143], delayed neuro‐ development during childhood [144], and reproductive disorders of man [145] and other negative effects. In the fetus, as the rapid growth and development occur during early development, the organs of the baby can be sensitive to the toxic substances; especially, the brain is more susceptible to neurotoxicants [146]. Increasing evidence suggests that prenatal pesticide exposure may have a permanent effect on children's behavior and intelligence. Besides, organophosphates are also hazardous compounds in the environment and public health. When children are exposed to pesticides in various ways at a young age, there is an observed negative effect on the development of the central nervous system [147]. Develop‐ mental impacts were mainly described as behavioral or cognitive, particularly those related to attention-deficit disorders and motor skills [119].

Experimental research has shown that many pesticides are endocrine disruptors that can disturb the functioning of various hormones throughout the body [148]. The production of thyroid hormone is thought to be inhibited by substances such as cyhalothrin, amitrole, pyrimethanil, and fipronil. Other pesticides may also alter thyroid hormone levels and potentially cause thyroid disease. Experimental studies *in vitro* support observations that the balance of sex hormones can be disrupted by exposure to certain pesticides. There is also evidence that fertility of both women and men may be decreased with increased pesticide exposure [119].

Studies showed that there are evidences of pesticide exposure and disorders in both hormonal regulation imbalance and immune system activities. The statistical results are associated with pesticide exposure and occurrence of some diseases. This finding cannot be ignored. The mechanisms of pesticide-induced diseases are not yet fully understood, but we now know that some key enzymatic activities in main metabolic pathways and/or the permeability of the ion channels are affected by them [149].

Moreover, some people carry susceptibility genes to the health effects of pesticides, and for that reason, they are likely to be more at risk than others. The questions on these epigenetical differences and developing policy approaches to ensure a high level of protection for mankind may remain insurmountable for a long time. In the meantime, people will continue with the routine application of pesticides to get more crops. On the contrary, the next generations, even they if are not exposed to pesticides, may also be at risk to these diseases due to epigenetical inheritance [119].

As mentioned by Allsop et al., many synthetic pesticides used in agriculture are persistent and pervasive in the environment. As a result, mankind is exposed to the mixture of pesticides via the food consumed and the environment around. Evidences suggest that more exposure means more toxic effect we will face. Although assays have been made to describe the toxicity of these kinds of interactions, there are no validated international guidelines in assessing these risks. In this case, we need to essentially rethink and change our systems to get rid of the exposure of pesticides. We must protect the health of vulnerable groups as well as the general population and whole ecosystems [119].

Reducing the use of pesticide strategies will not help us protect human health, because there are enormous kinds of pesticides in the market to be sold. In this case, people need to go towards ecological farming. This is a critical act in avoiding all risks. Protecting crops via a multilevel approach will help us increase the heterogeneity of the agricultural areas and this will provide a natural habitat for pollinators and natural pest control species. Thus, a functional biodiversity can be created if we can achieve an active vegetation management. A variety of crop types and cultivars increase both the fertility of soils and resistance to pests. Natural control agents, such as beneficial bacteria, viruses, insects, and nematodes, can be used in improving crop protection successfully [150].
