*Pesticides and Human Health*

*Emerging Contaminants*

somal rearrangements.

different types of studies.

**WHO Hazard Class**

Class Ia

Class Ib Highly Hazardous

Class II

Class III Slightly Hazardous

Class U

hazard

**Table 2.**

Extremely Hazardous

Moderately Hazardous

Products unlikely to present a

*Pesticides hazard classification by FAO.*

*7.2.2 Genotoxic and carcinogenic effects*

A genotoxic agent can be a physical, chemical or biological agent that can interact with the genetic material (DNA) causing alterations, damage or ruptures, and those that interfere with enzymatic processes of repair, genesis or polymerization of proteins involved in chromosome segregation. These alterations could lead to impaired embryonic development or be the initial steps in the development of cancer. Pesticides exposure can cause genomic damage. Genetic damage caused by pesticides is broadly classified into three classes; (i) Pre-mutagenic damage like DNA strand breaks and DNA adducts (ii) gene mutations like insertion, deletion, inversion and translocation (iii) chromosomal aberrations, including loss or gain of whole chromosome (aneuploidy), deletion or breaks (clastogenicity), and chromo-

Farmers exposed to pesticide mixtures in Greece had possible clastogenic (chromosome breakage cause mutation) and aneugenic (abnormal number of chromosomes) effect of pesticides on the genetic material. DNA methylation changes in the placenta were significantly associated with the maternal plasma concentrations of OCs in early pregnancy causing prenatal toxicity. OPs affect DNA methylation, induce the AChE gene expression and activate the NMDA glutamate receptors resulting in calcium influx in the post-synaptic neurons leading to degeneration. Genetic damage has been reported from exposure to malathion (OP), carbofuran (carbamate), triflumuron (Insect growth regulator), imidacloprid, acetamiprid

and thiamethoxam (neonicotinoid insecticides), pentachlorophenol (OC), Emamectin benzoate (used in agriculture, household, and veterinary medicine),

Cancer is characterized by an uncontrolled cell growth with limitless replication, resistance to apoptosis, alteration of growth factors (GFs), resistance to chemotherapy, metastasis and angiogenesis. Cancer develops as a result of multifactorial complex interactions of genetic and lifestyle factors including, diet, stress, physical and biological agents, infections, and exposure to the hazardous chemical substances. Pesticides exposure acts as a stimulant to cancer and chronic low-dose is considered one of the important risk factors for the increasing cancer incidence. **Table 3** presents a list of pesticides suggesting carcinogenicity in

> **Signal word Dermal LD50 (mg/Kg) Solid formulation**

Red VERY TOXIC <10 <40

Red TOXIC 10–100 40–400

Yellow HARMFUL 100-1000 400-4000

Blue CAUTION >1000 >4000

**Liquid formulation**

and tembotrione (novel post-emergence herbicide) (**Table 2**).

**Band color**

Green

**66**



**69**

*7.2.2.2 Leukemia*

*fungicides.*

**Table 3.**

*Pesticides and Human Health*

*DOI: http://dx.doi.org/10.5772/intechopen.93806*

Thyroid OP Malathion Agricultural health [51]

Ovarian OC Pp'-DDT Blood [55]

Pp'-DDE β-HCH Endosulfan

Cypermethrin Cyprodinil

Endosulfan

CAR Aldicarb

TRZ Penconazole Agricultural health [52] TRI Atrazine Agricultural health [53]

OP Diazinon Agricultural health [51]

PYR λ-Cyhalothrin BG-1 ovarian cancer

HYD Fenhexamid Mouse model with

OP Chlorpyrifos Human colorectal

Colorectal OC Pp'-DDE [57]

Brain OP Dichlorvos Male albino Wistar rats [59] *ToP, type of pesticide; OC, organochlorine insecticide; MoC, metabolites of chlordane; OP, organophosphate insecticide; PYT, pyrethroid insecticide; NPYT, natural pyrethroid insecticide; PHC, phenoxy-carboxylate herbicide; CHL, chlorophenoxy herbicide; BEN, benzoate herbicide; GLY, glycine herbicide; NEO, neonicotinoid insecticide; PHT, phthalimide fungicide; OB, organobromine insecticide; QUI, quinone algicide; IMI, imidazole fungicide; DIC, dicarboximide fungicide; MoV, metabolite of vinclozolin; CHP, chlorinated pyridine herbicide; ORG, organoarsenic herbicide; TRI, triazine herbicides; Mo2, metabolite of 2,4-D; Mod, metabolite of dinoseb dinitrophenol herbicide;*  α*CH,* α*-chloroacetamides herbicide; IMZ, imidazolinones herbicides; CAR, carbamate insecticide/nematicide; BEZ, benzamide, pyramide fungicide; BED, benzimidazole fungicide; TRZ, triazole fungicide; HYD, hydroxyanilides* 

Amitrole Nthy-ori-3-1 cell [54]

cells

cells

αCH Acetochlor Agricultural health [51]

transplanted BG-1 cells

adenocarcinoma H508

[56]

[56]

[58]

*7.2.2.1 Non-Hodgkin lymphoma and Hodgkin lymphoma*

*List of Pesticides Suggesting Carcinogenicity in different types of studies.*

cides) have been associated with significant risk of developing HL.

Non-Hodgkin lymphoma (NHL) is a diverse group malignancies and its incidence has increased worldwide. Patients with immune dysfunction are at a high risk to develop NHL. Studies have reported an elevated risk of NHL with exposure to several classes of pesticides. Terbufos (OP nematicide), dimethoate, malathion and chlorpyrifos (OP insecticide), and 2,4-D and dichlorprop (chlorophenoxy herbi-

Leukemia has been associated with occupational exposure with a higher risk in livestock farmers and golf course superintendents. The risk of chronic myelocytic leukemia (CML) and acute myeloblastic leukemia (AML) was found to be higher in women. Children whose parents used garden and indoor insecticides, or


*Pesticides and Human Health DOI: http://dx.doi.org/10.5772/intechopen.93806*

*Emerging Contaminants*

Prostate OC Pp'-DDT

Lindane

Malathion Carbaryl

DIC Vinclozolin MoV M2

TRI Simazine

2,4,5-T

Atrazine

Mo2 2, 4-dichlorophenol (DCP)

MoD Dinoseb amine

TRI Atrazine

Case-control [31]

Case-control [31]

RM1 cells [40]

Case control [31]

[32]

[38]

[47]

[47]

PC3 and DU145 cell

Endosulfan Human prostate cancer

OB Methyl bromide Agricultural health [33] OP Chlorpyrifos Prostate epithelial lines [34]

PYR λ-Cyhalothrin Prostate epithelial lines [34]

QUI Dichlone Case control [31]

CHL 2,4-D Case control [31]

CHP Picloram Histopathology [39] ORG Cacodylic acid Case control [31]

GLY Glyphosate Prostate epithelial lines [34]

PYT Cypermethrin Lewis lung cancer cells [42] αCH Acetochlor Agricultural health [43]

OC Pp'-DDT Serum levels [45]

CAR Carbaryl Toxicological [46] BEZ Fluopyram Female rat [48] BED Carbendazim Toxicological [46] BEN Dicamba Agricultural health [49]

OC Endosulfan Human liver carcinoma

αCH Acetochlor Human liver carcinoma

Stomach TRI Atrazine Agricultural health [50]

Pp'-DDE Toxicological [46]

cells (HepG2)

cells (HepG2)

Lung cancer OP Diazinon Epidemiological [41]

Bladder IMZ Imazethapyr imazaquin Agricultural health [44]

IMI Prochloraz PC-3 prostate cancer

Dimethoate Agricultural health [35]

Bifenthrin PC3 human [36] Deltamethrin Prostate cancer cell [37]

cells

2,4-DB Histopathology [39]

**68**

Hepatocellular carcinoma

*ToP, type of pesticide; OC, organochlorine insecticide; MoC, metabolites of chlordane; OP, organophosphate insecticide; PYT, pyrethroid insecticide; NPYT, natural pyrethroid insecticide; PHC, phenoxy-carboxylate herbicide; CHL, chlorophenoxy herbicide; BEN, benzoate herbicide; GLY, glycine herbicide; NEO, neonicotinoid insecticide; PHT, phthalimide fungicide; OB, organobromine insecticide; QUI, quinone algicide; IMI, imidazole fungicide; DIC, dicarboximide fungicide; MoV, metabolite of vinclozolin; CHP, chlorinated pyridine herbicide; ORG, organoarsenic herbicide; TRI, triazine herbicides; Mo2, metabolite of 2,4-D; Mod, metabolite of dinoseb dinitrophenol herbicide;*  α*CH,* α*-chloroacetamides herbicide; IMZ, imidazolinones herbicides; CAR, carbamate insecticide/nematicide; BEZ, benzamide, pyramide fungicide; BED, benzimidazole fungicide; TRZ, triazole fungicide; HYD, hydroxyanilides fungicides.*

#### **Table 3.**

*List of Pesticides Suggesting Carcinogenicity in different types of studies.*

#### *7.2.2.1 Non-Hodgkin lymphoma and Hodgkin lymphoma*

Non-Hodgkin lymphoma (NHL) is a diverse group malignancies and its incidence has increased worldwide. Patients with immune dysfunction are at a high risk to develop NHL. Studies have reported an elevated risk of NHL with exposure to several classes of pesticides. Terbufos (OP nematicide), dimethoate, malathion and chlorpyrifos (OP insecticide), and 2,4-D and dichlorprop (chlorophenoxy herbicides) have been associated with significant risk of developing HL.

#### *7.2.2.2 Leukemia*

Leukemia has been associated with occupational exposure with a higher risk in livestock farmers and golf course superintendents. The risk of chronic myelocytic leukemia (CML) and acute myeloblastic leukemia (AML) was found to be higher in women. Children whose parents used garden and indoor insecticides, or

#### *Emerging Contaminants*

whose mothers had been exposed while pregnant had increased rates of all types of leukemia. Children living on farms and those exposed to household pesticides have increased risk of leukemia. Association between occupational exposure to pesticides and chronic lymphocytic leukemia (CLL) has been reported from Spain. A nationwide study in France showed a moderate increase in incidence of childhood AL in municipalities where viticulture is common.
