An-Najah National University

Faculty of Graduate Studies

Water and Environmental Engineering Master

Date of Submission: 19/5 / 2023

Supervisor: Dr. Abdelhaleem Khader

Group members:
1-Afif Aqad
2-Abeer Abu-Ayhour
3-Taqwa Mohammed
4-Majeda Al-Haj Hussein
 The Impact of Environmental Factors on The Risk of
Developing Parkinson’s Disease. A Case Study: Tulkarm
Governorate-Palestine.

Abstract:

This Study investigates the impact of heavy metals on the development of Parkinson's
disease in Tulkarm. Parkinson's disease is a neurodegenerative disturbance that affects
millions of people worldwide. While genetic factors have been involved in the evolution
of the disease, there is increasing evidence to suggest that environmental factors may also
play a significant role, understanding the environmental factors connected with Parkinson's
disease is necessary for public health to inhibit and reduce the disease among these factors
air, water and soil pollution, mainly pollution caused by heavy metals. The study involved
distributing questionnaires to patients in the Tulkarm Governorate, which revealed the
highest rate of Parkinson's disease in the village of Ramin Therefore , Ramin was chosen
to be the starting point of search. The research team also collected 5 drinking water
samples from different sources in Ramin and conducted tests on these samples ,and the
results showed that it is not a cause for concern. Therefore, the study concludes that water
contamination is not a contributing factor to Parkinson's disease in Ramin. The paper
highlights the need for further research to identify other factors that may effect on the
evolution of the disease. In conclusion, this research provides important ideas into the
potential causes of Parkinson's disease in Ramin. While water contamination does not
appear to be a contributing factor, continued research efforts are needed to consider the
number of samples, and the season of the year in which the samples will be taken and to
identify other environmental factors that may be responsible for the disease.

Keywords— Parkinson’s disease; Environmental factors; Heavy metals; Drinking Water; Tulkarm;
Palestine

1. Introduction

Parkinson's disease (PD) is the second most common neurological disorder after
Alzheimer's[1] and the fastest growing[2] worldwide, It is characterized as a chronic
neurodegenerative condition in the brain associated with low levels of dopamine due to a
decrease in dopaminergic neurons in subansia nigra. This causes motor symptoms such as
tremor and dyskinesia in addition to non-motor symptoms such as constipation. The
development of these symptoms and complications leads to higher rates of disability and
care requirements[3]–[5]. The prevalence of Parkinson's disease (PD) has doubled in the
past 25 years, with global estimates in 2019 showing that more than 8.5 million people
suffer from Parkinson's disease. In addition, it is estimated that in 2019, PD led to 5.8
million disability-adjusted life years, an 81% increase since 2000 and caused 329,000
deaths, an increase of more than 100% since 2000 [5], and future estimates indicate that
PD will affect more than 9 million people. by 2030[6] and 13 million by 2040[1], [2], [7]. Little
is known about the pathophysiology and etiology of Parkinson's disease despite its
prevalence. Studies indicate that PD is a multifactorial disease, in which genetic and
environmental factors contribute to causing the disease, but the molecular mechanisms
linking these two major modifiers of the disease remain obscure[8]. The contribution of
genetic factors is estimated to be around 10-15% for cases of early-onset Parkinson's
disease, indicating that the risk of Parkinson's disease is still largely influenced by
external factors These non-genetic factors continue to be underappreciated
and understudied[2], [9] .

The term "environment" includes any non-internal factor, such as pathogenic infection,
head trauma, diet, pharmaceuticals, nutritional supplements, drug use, and other
physiological stressors (for example, post-traumatic stress disorder). Cumulative
evidence in many scientific papers indicates a close link between the role of
environmental toxins and the risk of developing Parkinson's disease. Examples of
environmental toxins include air pollution, water, metal ions, soil, and exposure to
pesticides for their role in causing oxidative stress, mitochondrial dysfunction, and
chronic neuroinflammation[2], [10].

Regarding pesticides, they are one of the well-documented harmful factors that
contribute to disease. Due to the long half-life of these chemicals and their ability to
accumulate in food chains, the risks may be higher than studies suggest. Pesticides can
enter the human body through inhalation, ingestion, or skin contact, making them
strongly associated with water, air, and soil pollution[10], [11].

As for heavy metal pollution, research indicates that it is an important factor in the onset
of Parkinson's disease. Heavy metals play a role in cell maintenance, but growing
evidence suggests that they can cause disruptions with an increased rate of PD. Metals
disrupt molecular processes and lead to oxidative stress, DNA damage, mitochondrial
dysfunction, and persistence[1], [12], [13].

Regarding air pollution, research on the impact of ambient air pollution on Parkinson's
disease remains controversial. Epidemiological studies have reported conflicting results.
Some studies have found that long-term exposure to PM2.5, NO2, and O3 may increase
the risk of developing Parkinson's disease, but the evidence is not yet conclusive. In this
study, we will focus on factors related to water and soil pollution. In this study, we will
be focusing on environmental toxins as one of the environmental factors. Wherever
environmental factors are mentioned in this study, they specifically refer to
environmental toxins[9], [14], [15]
In Palestine, there is a scarcity of research related to Parkinson's disease, as well as
studies on the impact of environmental factors on increasing the risk of the disease, in
addition to the lack of official statistics and data on the number and distribution of
patients. All of this presents a challenge in determining the optimal location for
conducting such a study. Tulkarm Governorate was chosen as the number one site for this
investigation due to its complex environmental conditions, which may play a role in
increasing the risk of Parkinson's disease. Tulkarm is located in the northwestern part of
the West Bank, with a population of 186,760[16], which represents 12% of the population
of the West Bank. Most of its population is engaged in agriculture. Since the 1980s, many
industries have been relocated to areas in the western part of Tulkarm, leading to
increased air pollution. Among these factories is Gishori, which produces agricultural
pesticides, insecticides, and fertilizers. Analysis of some heavy metals in rainwater, soil,
and groundwater showed that the concentrations of these elements were higher in areas
close to the factories, such as B, Ni, Pb, Cu, Cd, Fe, Cr, Mn, Co, and Zn. Furthermore, an
interesting finding was that the analysis of a rainwater sample showed much higher levels
of nitrogen oxides and chlorine[17], [18].

In terms of drinking water, groundwater is the main source of water in Tulkarm, and the
type of water for most wells is alkaline-saline with high levels of bicarbonates and
alkalinity. Studies have shown high levels of nitrate concentrations exceeding the World
Health Organization's standards of 45 mg/L for drinking water. This increase is primarily
attributed to pollution-causing activities such as intensive irrigation, sewage treatment,
and excessive land fertilization. Water consumption is estimated at 85 liters per person
per day[19]. Regarding sewage, the main sewage valley in the area is called Wadi Zomar,
with a length of about 22 km and a width of 5 km. Wadi Zomar is heavily polluted due to
human activities, leading to serious health problems. Wadi Zomar is used to drain sewage
from the cities of Nablus and Tulkarm and the villages located on the banks of the valley.
In addition to Wadi Zomar, sewage is disposed of through many absorption wells, posing
a significant threat to groundwater[20]. Furthermore, other studies have shown that
Tulkarm residents have among the highest rates of cancer, asthma, eye health disorders,
and respiratory problems compared to residents of other areas[18].

In this study, we utilized the descriptive epidemiology methodology to examine the

impact of environmental factors on the development of Parkinson's disease. Descriptive
epidemiology is a methodology that involves analyzing and interpreting data on the
distribution and patterns of disease occurrence in a population. This methodology seeks to
provide a detailed understanding of the disease and its various characteristics, including
its prevalence, incidence, and risk factors. By using this approach, we can identify
potential environmental factors that may contribute to the development of Parkinson's
disease and inform public health strategies for prevention and control. Overall, descriptive
epidemiology plays a critical role in identifying health disparities and informing public
health policy and practice.

This study aims to investigate the effect of heavy metals on the risk of developing
Parkinson's disease in Tulkarm governorate and to link these pollutants to their potential
sources, which can guide decision makers to take the necessary measures to protect public
health.

2. METHODOLOGY

2.1. Study area description

Based on the questionnaires we identified Ramin as a good starting point for the research.
Ramin is a Palestinian village located in the eastern part of the Tulkarm governorate as
shown in Figure 1 . According to the Palestinian Central Bureau of Statistics, its
population 2,203 in 2023. The majority of the village's inhabitants work in agriculture,
particularly olive and fig cultivation, as well as livestock breeding. The village's main
sources of water are the Anabta well, located in the nearby village of Anabta, which
provides the majority of the village's water supply, and AL-Qantarah spring located 2 km
east of the village. In terms of sanitation, around 85% of the wastewater in Ramin is
isposed of using absorption pits.

Figure 1: Tulkarm Governorate

2.2.1. Data collection and questionnaires

We collected 32 questionnaires for patients who were born or raised in Tulkarm that
Included Information was obtained concerning: sex, year of birth , age of clinical onset,
occupation, lifestyle habits , prior history of encephalitis, major tranquilizer usage, family
history of parkinsonism or other neurological disorders, the residence of the family when
the patient was born, residence of the patient during the various periods of his life and the
source of drinking water during that's periods. This information was reported in 2023 and
obtained by distributing questionnaires to patients through local hospitals and clinics, to
ensure that the patient's identities remain confidential.

2.2.2. Ethical Considerations

The Institutional Review Boards (IRB) of An-Najah National University and the
Palestinian Health Authority approved every aspect of the study protocol, including the
use of and access to the patients’ data. Furthermore, before initiating data collection, we
properly explained all parts of the questionnaire to patients and received their verbal
consent.

2.3. Sampling

Ramin was visited and 5 samples were taken in plastic bottles after washing the bottles
five times with the water of the sample to be taken and it was kept in a dark place at a
temperature of 4±1 degrees Celsius. The samples taken from the sources that supply
Ramin village with drinking water, which are as follows:

1. AL-Qantarah spring.

2- Anabta well that supplies water to ramin.

3- A tank containing a mixture of water of AL-Qanatrah spring and Anabta well.

4- Water tap after passing through the network and household tanks.

5- Tap water after passing through the network and before going through household tanks.

2.4. Laboratory Analysis

the collected water samples were analyzed in a certified laboratory for the presence of
potential contaminants, such as heavy metals. The laboratory followed standard analytical
techniques, including inductively coupled plasma mass spectrometry (ICP-MS), the
collected water samples were analyzed in Water and Environmental Studies Institute ,
An-Najah National University- Nablus (WEST) laboratory, such as Analysis heavy
metals for 30 metals: silver (Ag), aluminum (Al), Arsenic (As), barium (Ba), boron (B),
beryllium (Be), Bismuth (Bi), calcium (Ca), cadmium (Cd), cobalt (Co), chromium (Cr),
copper (Cu), iron (Fe), Gallium (Ga), potassium (K), Lithium (Li),magnesium (Mg),
manganese (Mn), molybdenum (Mo), sodium (Na), nickel (Ni), lead (Pb), Rubidium (Rb),
Selenium (Se) ,Strontium (Sr), Tellurium (Te), titanium (Ti), Uranium (U),vanadium (V),
and zinc (Zn), These analyses were performed without prior knowledge of the source of
the water sample. Methods used for chemical analysis were similar to those described
elsewhere and the laboratory followed standard analytical techniques, including
inductively coupled plasma mass spectrometry (ICP-MS)

2.5. Statistical analysis

This study contains descriptive Epidemiology statistics such as means, standard

deviations, were calculated to summarize the data with using excel (Microsoft).

2.6. Limitations

This study cannot establish causality between exposure to environmental factors and
Parkinson's disease as it is an observational study. Furthermore, the accuracy of the
questionnaires may also be limited by the patients' received information from the
ability to recall. In addition, there are still two soil samples under examination in the
laboratory, the results of which have not yet been received.

3. Result and Discussion

After collecting 32 questionnaires from patients in the Tulkarem region, and through the
patients’ answers to these questionnaires, we found that there are two other patients
for whom questionnaires were not made, one of them died a year before the
questionnaires were conducted, which makes the total number of patients in the
Tulkarem region 34 patients.
The distribution of disease cases among the city of Tulkarem and its villages was as
the percentage of infection between shown in the attached diagram in Figure 2, where
females and males was equal (14 females & 14 males).
 12
10

No.of patients
8
6
4
2
0

Figure 2: Clustered vertical graph of the distribution of patients in Tulkarm Governorate

As shown in Figure 2, and although the population of Tulkarm has the highest number of
patients, however, Ramin had the highest number of patients in relation to the
population with 4 females and 3 males as shown in Figure 3.

Figure 3:Annular graph of the proportion of patients to the population

The Based on these percentages we identified Ramin as a starting point for the research.
The results in Table 1 present the analysis of the five drinking water samples that were
collected from several sources in the village of Ramin by ICP device.
 Table 1: Results for analyzed drinking water samples in Ramin

Sample No 1 2 3 4 5
Metal Mean Concentration ( ppb)
Ag 0.0015 0.0105 0.006 0.002 -0.002
Al 1.0915 1.6083 1.358 0.499 1.509
AS 1.64 1.985 1.502 1.64 1.63
B 49.645 48.435 43.91 46.01 41.4
Ba 219.34 196.635 182.075 191.89 166.65
Ca 81778.1 68587.15 64709.35 60393.6 61878.8
Cd -0.045 -0.055 -0.055 -0.03 -0.07
Cr 19.295 18.55 16.99 15.85 15.92
Cu 0.53 6.575 1.15 0.69 1.49
Fe 167.17 130.045 116.185 121.31 113.43
Ga 2.14 1.94 1.83 1.89 1.66
K -7334.2 -7901.99 -6946.63 -7371.3 -6256.9
Li 2.99 2.11 2.035 1.98 1.93
Mg 12286.3 29179.15 25703.98 25563.3 24615.6
Mn 4.04 0.05 0.065 0.77 0.16
Mo 0.41 1.34 1.1 1.04 1.04
Na 43444.6 60425.84 54762.35 55679.7 51469.1
Ni 5.985 3.7 3.605 3.06 3.21
Pb 0.045 0.42 0.05 0.06 0.06
Rb 2.415 1.23 1.18 1.19 1.12
Se 0.405 4.315 4.26 2.87 3.93
Sr 497.88 335.375 326.8 312.69 308.13
U 0.645 1.355 1.17 1.14 1.16
V 6.375 7.655 7.175 7.08 6.7
Zn 118.395 13.49 11.29 67.57 53.55

The results in Table 1 show that the concentrations of the elements were within the
permissible limit for their concentrations in the drinking water

4. Conclusion and Recommendations

largest Heavy metal concentrations were found in the order Ca > Na> Mg> Sr > Ba > Fe
in drinking water in Ramin. were found within the permissible limits set by WHO and
EPA. is concluded that, the drinking water in the study area does not pose chronic health
risk that Related to heavy metals. This finding highlights the need for further research to
identify other contaminants in drinking water other than heavy metals Additionally, it is
essential to investigate contaminants for other environment factors that may impact the
disease’s development in such as soil and air. research team recommends to increase the
sample size, this will enhance the reliability and validating of the findings, take samples in
summer season to consider the dilution that the rains may have caused to the contaminants
in winter season ( where our sample taken in). By adopting these recommendations, we
can enhance our understanding of the relationship between the disease and environmental
factors and take protective steps towards management and prevention..

5. References

[1] S. Pyatha, H. Kim, D. Lee, and K. Kim, “Association between Heavy Metal
Exposure and Parkinson’s Disease: A Review of the Mechanisms Related to
Oxidative Stress,” Antioxidants, vol. 11, no. 12, 2022, doi:
10.3390/antiox11122467.
[2] B. R. De Miranda, S. M. Goldman, G. W. Miller, J. T. Greenamyre, and E. R.
Dorsey, “Preventing Parkinson’s Disease: An Environmental Agenda,” J.
Parkinsons. Dis., vol. 12, no. 1, pp. 45–68, 2022, doi: 10.3233/JPD-212922.
[3] S. Safiri et al., “The burden of Parkinson’s disease in the Middle East and North
Africa region, 1990–2019: results from the global burden of disease study 2019,”
BMC Public Health, vol. 23, no. 1, pp. 1–12, 2023, doi: 10.1186/s12889-023-
15018-x.
[4] R. Jia et al., “The Relationship between Iron and LRRK2 in a 6-OHDA-Induced
Parkinson’s Disease Model,” Int. J. Mol. Sci., vol. 24, no. 4, 2023, doi:
10.3390/ijms24043709.
[5] World Health Organization, “Launch of WHO’s Parkinson disease technical brief,”
14 June 2022. [Online]. Available: https://www.who.int/news/item/14-06-2022-
launch-of-who-s-parkinson-disease-technical-brief. [Accessed: 05-May-2023].

[6] A. Bougea et al., “Ambiental Factors in Parkinson’s Disease Progression: A

Systematic Review.,” Medicina (Kaunas)., vol. 59, no. 2, 2023, doi:
10.3390/medicina59020294.
[7] A. Zirra et al., “Gender Differences in the Prevalence of Parkinson’s Disease,”
Mov. Disord. Clin. Pract., vol. 10, no. 1, pp. 86–93, 2023, doi:
10.1002/mdc3.13584.
[8] E. Angelopoulou, Y. N. Paudel, S. G. Papageorgiou, and C. Piperi,
“Environmental Impact on the Epigenetic Mechanisms Underlying Parkinson’s
Disease Pathogenesis: A Narrative Review,” Brain Sci., vol. 12, no. 2, pp. 1–24,
2022, doi: 10.3390/brainsci12020175.
[9] H. Khreis et al., “Impact of long-term air pollution exposure on incidence of
neurodegenerative diseases: A protocol for a systematic review and exposure-
response meta-analysis,” Environ. Int., vol. 170, no. May, p. 107596, 2022, doi:
10.1016/j.envint.2022.107596.
[10] H. Reichmann et al., “Life style and Parkinson’s disease,” J. Neural Transm., vol.
129, no. 9, pp. 1235–1245, 2022, doi: 10.1007/s00702-022-02509-1.
[11] H. Chen and B. Ritz, “The search for environmental causes of Parkinson’s disease:
Moving forward,” J. Parkinsons. Dis., vol. 8, no. s1, pp. S9–S17, 2018, doi:
10.3233/JPD-181493.
[12] M. A. Gonzalez-Alvarez, D. Hernandez-Bonilla, N. I. Plascencia-Alvarez, H.
Riojas-Rodriguez, and D. Rosselli, “Environmental and occupational exposure to
metals (manganese, mercury, iron) and Parkinson’s disease in low and middle-
income countries: A narrative review,” Rev. Environ. Health, vol. 37, no. 1, pp. 1–
11, 2022, doi: 10.1515/reveh-2020-0140.
[13] F. Okechukwu Ohiagu, P. C. Chikezie, C. C. Ahaneku, and C. M. Chikezie,
“Human exposure to heavy metals: toxicity mechanisms and health implications,”
Mater. Sci. Eng. Int. J., vol. 6, no. 2, pp. 78–87, 2022, doi:
10.15406/mseij.2022.06.00183.
[14] C. Han, Y. Lu, H. Cheng, C. Wang, and P. Chan, “The impact of long-term
exposure to ambient air pollution and second-hand smoke on the onset of
Parkinson disease: a review and meta-analysis,” Public Health, vol. 179. Elsevier
B.V., pp. 100–110, Feb. 01, 2020. doi: 10.1016/j.puhe.2019.09.020.
[15] R. Liu, M. T. Young, J. C. Chen, J. D. Kaufman, and H. Chen, “Ambient air
pollution exposures and risk of parkinson disease,” Environ. Health Perspect., vol.
124, no. 11, pp. 1759–1765, Nov. 2016, doi: 10.1289/EHP135.
[16] PCBS, “Preliminary Results of the Population, Housing and Establishments
Census 2017; Palestinian Central Bureau of Statistics: Ramallah, Palestine, 2018;
p. 82,” 2017.
[17] G. I. Omar and S. I. AlKhalil, “A study of the environmental impacts of the
Gishori Industrial Complex on plant diversity in Tulkarm, Palestine,” Jordan J.
Biol. Sci., vol. 12, no. 4, pp. 487–494, 2019.
[18] B. Natsheh, “The Impact of Gishouri Factories on Soil Pollution in Tulkarm Area:
A Case Study,” Resour. Environ., vol. 6, no. 4, pp. 72–79, 2016, doi:
10.5923/j.re.20160604.02.
[19] M. Ghanem and N. Samhan, “Groundwater pollution assessment in {T}ulkarem
area, {P}alestine,” J. {E}arth {S}ciences {G}eotechnical {E}ngineering, vol. 2, no.
1, pp. 1–16, 2012.
[20] S. Khayat, A. Marei, B. Natsheh, and N. Abu-Khalaf, “Mechanisms of
Groundwater Pollutants Transport in Tulkarm Area / Palestine,” Resour. Environ.,
vol. 2, no. 6, pp. 281–290, 2012, doi: 10.5923/j.re.20120206.06.