Introduction
Chronic exposure to pesticides leads to biochemical changes in the body [1, 2], dur to destructive and degenerative effects of pesticides on many body organs [3, 4, 5, 6]. Exposure to low levels of pesticides can increase liver enzymes [7, 8]. Exposure to pesticides such as organochlorine, organophosphorus, and pyrethroids is associated with an increase in serum lipid levels [9]. Exposure to pesticides is one of the risk factors for cardiovascular diseases and metabolic syndrome [9, 10]. There are several pesticide production factories in Guilan province, Iran. Considering the impact of pesticides on increasing the risk of dangerous health problems and the shortage of necessary protection equipment, and the lack of knowledge of workers how to reduce exposure and direct contact with these substances, this study aims to compare the biochemical parameters in workers with exposure and non-exposure to pesticides in Rasht, Guilan, Iran.
Materials and Methods
This cross-sectional study was conducted on 99 male workers exposed to pesticides and 107 male workers without exposure in a pesticide production factory in Guilan, Iran. They were selected by a convenience sampling method in 2020. Demographic characteristics such as age, Body Mass Index (BMI), blood pressure, etc., as well as clinical characteristics including the respiratory symptoms (cough, shortness of breath, etc.), neurological symptoms (fatigue, tremors, cramps, muscle weakness, etc.), psychological symptoms (sleep disorders, anxiety, etc.) and skin symptoms (redness, itching, etc.) were collected from the occupational health records of the participants. Inclusion criterion was at least 6 months of work experience in the factory and the exclusion criterion was incomplete occupational health records. The study biochemical parameters were Fasting Blood Sugar (FBS), total cholesterol, High-Density Lipoprotein (HDL), Low-Density Lipoprotein (LDL), triglyceride (TG), Creatinine (Cr), Blood Urea Nitrogen (BUN), alanine transaminase (ALT), Aspartate Transaminase (AST) and Alkaline Phosphatase (ALP). Statistical analysis was performed in SPSS software, version 16 using the Shapiro-Wilk test, Mann-Whitney U test, Chi-square test, and Fisher’s exact test. The significance level was set at 0.05.
Results
The mean±SD age of participants was 38±7.74 years. Their mean work experience, BMI, systolic and diastolic blood pressures were 11.19±6.21 years, 25.94±3.36 kg/m2, 125.19±8.2 mmHg, and 79.98±5.53 mmHg, respectively. Most of the workers were married (n=165, 80.9%) and about 20.4% (n=42) were smoking. Demographic information of workers in both groups are reported in Table 1.


The most common symptoms among exposed workers were cough (13.1%), headache (8.7%), sleep disorders (7.8%), and itchy skin (6.8%).
The comparison of biochemical parameters between exposed and unexposed groups showed that the mean levels of FBS, BUN, Cr, and ALP were significantly higher in the exposed group (P<0.05). About 27.3% of the workers in the exposed group were significantly prediabetic. However, the mean level of liver enzymes ALT and AST were not significantly different between the two groups (P>0.05) (Table 2).


Of 206 participants, 11 (5.3%) had thrombocytosis (PLT>450×103 mL). The frequency of thrombocytosis was significantly higher in the exposed group compared to the non-exposure group (9.09% vs. 1.9%) (P=0.028). In comparing the frequency of thrombocytosis based on years of work experience, results showed that workers with a work experience of >11 years had higher rate of thrombocytosis compared to those with a work experience <11 years (90.9 % vs. 9.1%), (P=0.003) (Table 3).


Discussion
The high use of pesticides has increased the concern about its possible adverse effects on human health and the environment. Excessive exposure to pesticides causes toxic changes in liver and kidney enzymes [11, 12]. Elevated Cr level in response to pesticide exposure is an indicative of kidney problems and may be the result of glomerular dysfunction. A study by Yassin et al., showed that some renal function parameters such as BUN and Cr, were significantly higher in farmers who exposed to pesticides, [6] which is consistent with our results. Other studies have also reported similar results [13, 14, 15]attitude and practices of Kuwaiti farmers regarding the safe use of pesticides. A total of 250 farmers participated in this study through in-depth interviews and observations on-farm. The majority of the farmers acknowledged that pesticides were harmful to their health (71%).
The results of our study showed that the ALP level was higher in the exposed workers, but no significant difference was observed in the serum level of ALT and AST. In previous studies, it has been shown that the duration of contact has a relationship with the increase of liver enzymes. In Kori et al.’s study, the liver enzymes ALP, ALT, and AST were higher in the exposure group, which indicates the development of liver problems and hepatotoxicity caused by pesticides [16]. The elevated levels of FBS in workers with exposure to pesticides has also been reported in various studies [9, 17], consistent with our results. In our study, about 9% of workers with a work experience of >11 years had thrombocytosis. The frequency of symptoms such as headache, itchy skin, cough, and sleep disorders were higher in the exposed group, which is consistent with the findings of other studies [18, 19, 20] hematological findings were assessed in workers in an insecticide manufacturing plant. Hematological parameters and clinical symptoms were recorded in 99 workers exposed to insecticides and 107 workers not exposed to them in a cross-sectional study. Assessment of the hematological results showed a higher prevalence of thrombocytosis in the exposed group than the non-exposed group (P<0.05. Overall, it can be concluded that chronic exposure to pesticides can cause thrombosis, changes in biochemical parameters, and clinical symptoms such as headache, itching, cough, and sleep disorders. 

Ethical Considerations
Compliance with ethical guidelines
This study was approved by the Research Ethics committee of Guilan University of Medical Science, Rasht, Iran (Code: IR.GUMS.REC.1399.632). Informed consent was obtained from all participants in this study.

Funding
The paper was extracted from the MD thesis of Maryam Joshan and Fatemeh Rahattalab at the Razi Clinical Research Development Unit, Razi Hospital of Guilan University of Medical Sciences.

Authors' contributions
Design: Mirsaeed Attarchi; Writing the initial draft: Fatemeh Nejatifar; supervision: Hamid Mohammadi Kojidi; Data analysis: Zahra Atrkar Roushan; Editing: Niloofar Faraji; Data collection: Maryam Joshan, Fatemeh Rahattalab and Roholah Amini.

Conflicts of interest
The authors declare no conflict of interest.

Acknowledgements
The authors would like to thank all participants for their cooperation in this study.