Pesticides Exposure in Relevance to Cancer Risk

Introduction

The presence of a detectible pesticide residue in an edible food should be at levels far lower than those that are considered health risks as indicated by USDA’s Pesticide Data Program. Western epidemiological and agricultural health studies reported the effect for pesticides-associated carcinogenesis in multiple human organ systems such as breast cancer, prostate cancer, lung cancer, brain cancer, testicular cancer, colorectal cancer, pancreatic cancer, esophageal cancer, stomach cancer, brain cancer, skin cancer, and non-Hodgkin lymphoma. There is mounting evidence on the link of pesticide's exposure with the incidence of cancer at higher rates among pesticides manufacturing workers, applicators, farmers, and farms inhabitants. In many countries, agricultural workers and farmers as compared to the general population have higher rates of cancer incidence, for example, farming communities in the United States have higher rates of leukemia, non-Hodgkin lymphoma, multiple myeloma, and soft tissue sarcoma, as well as cancers of the skin, lip, stomach, colorectal, brain, and prostate [1]. Even though no one set of risk factors explains these higher cancer rates, the range of environmental exposures in the farming community is of concern; where farmers, farm workers, and farm family members are exposed to substances such as pesticides, engine exhausts, solvents, dusts, animal viruses, fertilizers, fuels, and specific microbes that may account for these elevated cancer rates. There is growing epidemiological evidence on the putative positive association between long-term exposure to pesticides in occupational settings and an elevated rate of cancer, but data on biological links are scarce to draw any conclusion. Risk factors that are often related to the risk for cancer incidence are generally classified as non-modifiable or modifiable factors. Non-modifiable factors that are often related to cancer incidence rates are age, gender, family history, and genetic predisposition. Modifiable risk factors that are often discussed with increased cancer risk are smoking, low intake of dietary antioxidants, B-vitamins deficiency and Obesity [2]. Cancer may also be linked to modifiable risk factors that are classified as environmental; these environmental risk factors can be altered or changed as they relate to personal behaviors, dietary intake, lifestyle and occupation [3]. Pesticides exposure among general population represents an environmental risk factor in relation to cancer development, and represents a missing component of the present knowledge as there is a lack of evidence in the current available literature. Pesticides are unique, intrinsically toxic chemicals designed to be deliberately spread into the environment to kill off pests. They are comprised of many different categories of chemicals and approximately 5.2 billion pounds were used worldwide in 2006 and a similar amount in 2007, but only 1% of this amount reaches the target pests at lethal doses [4, 5]. Herbicides account for the largest portion of that amount, followed by other pesticides, insecticides and fungicides. Exposure to pesticides can occur through multiple pathways (e.g. food, drinking water, residential, occupational) and routes (oral, inhalation, dermal). Although the contribution of a given route or pathway to overall exposure depends on the pesticide, it is the totality of exposure, by multiple routes and multiple pathways, what determines the risk [6]. The type and severity of adverse health effects of pesticides are determined by the individual chemical category, the dose and the duration of exposure and the exposure route [5, 6]. Given that humans are much larger than the target species for pesticides, they are expected to be unaffected by small amounts of these compounds. However, pesticides are indeed toxic to humans not only at high doses, responsible for acute poisonings, but even in low doses, as there are mixtures of pesticides that might synergize through the long-term exposures and lead to an array of health effects (respiratory, reproductive and developmental toxicity) and human chronic diseases, including cancer. Pesticides are often applied in mixtures to crops, their residues can Waly MI. Pesticides Exposure in Relevance to Cancer Risk. J Agri Res 2017, 2(2): 000129.

be found in foods, drinking water, and aquatic environment, including surface waters that support aquatic life [7]. Assessment of pesticide exposure to humans is generally based on measurement of non-specific metabolites in urine and hair samples, which enables the assessment of the type of exposure and to associate this exposure to relevant health issues. In the European Union and the United States, legislation has been laid down regulating the presence of pesticides residues in food products by setting maximum residue levels (MRL) of individual pesticides. As long as the individual residues do not exceed the MRLs, the presence of multiple residues in one sample as such is not a reason to be considered as not compliant with the MRL legislation. The international agency for research on cancer (IARC), United States national toxicology program (US NTP), United States environmental protection agency (US-EPA), and toxic release inventory (TRI) have indicated that in humans, the carcinogenic properties of pesticides can be influenced by a series of complex factors including age, sex, individual susceptibility, amount and duration of exposure, and simultaneous contacts with other cancer causing chemicals. In experimental animals’ models, the carcinogenic mechanisms of pesticides were explored in their potential to affect genetic material either directly via induction of structural or functional damage to chromosomes, DNA, and Histone proteins, or indirectly via disrupting the profile of gene expression through impairment of cellular organelles like mitochondria and endoplasmic reticulum, nuclear receptors [8, 9]. Human exposure to low-dose pesticide mixtures may occur from environmental or nutritional sources (foods and drinking water) and may have a long-lasting and negative health impact in the long-term, some being connected with the increase of cancer in humans as evidenced in Western countries [10]. Despite many articles describe the carcinogenic effects of exposure to pesticides and their mixtures, relatively little information is available on the nature of metabolic interactions (independent, dose addition or interaction) that may occur between the constituents of a pesticide mixture, and results in biological events favoring cancer incidence via inhibition of detoxifying enzymes, increasing the cytotoxicity, and stimulating or activating oncogenes [11]. Based on rising evidence given by epidemiological and agricultural health studies associated with exposure to pesticides and carcinogenesis, the International Agency Copyright© Waly MI.

for Research on Cancer (IARC) has considered chronic low-dose exposure to pesticides as one of the important risk factors for cancer incidence. Therefore, carcinogenicity tests are now applied to detect carcinogenic potential of pesticides before allowing them to be marketed. These carcinogenicity testing is conducted by the Environmental Protection Agency (US- EPA), and it is a long-term (around two years) rodent bioassay using two species of both sexes, and according to a new list of chemicals evaluated for carcinogenic potential by EPA's pesticide program published in 2010, more than 70 pesticides have been classified as a probable or possible carcinogen [12]. This classification has been accomplished based on the information extracted from animal genotoxicity and mutagenicity- based studies, and there is a need for human-based clinical trials to address these issues.

Conclusion

Taken together, pesticides-associated carcinogenesis as discussed above is considered as the major disorder affecting public health in the 21st century. The relationship between cancer risk and environmental exposures, particularly pesticides increasingly continues to strengthen. Near to all studies carried out in the area of pesticides, and cancer are categorized in the field of epidemiologic evidence or experimental animal investigation with no mechanistic insight into the cancer development. It should not be forgotten that these mechanisms work alongside or sequentially rather than singly, or they even can potentiate genetically susceptible individuals.