ABSTRAK BLOOD PRESSURE FLUCTUATION AND NEUROBEHAVIORAL PERFORMANCE EFFECT OF LONG TERM ORGANOPHOSPHATES (OPs) PESTICIDE EXPOSURE AMONG THE ADOLESCENTS IN AGRICULTURAL AREA Latar belakang: Pestisida organofosfat (OP) banyak digunakan dalam praktek pertanian. Pestisida ini dilaporkan mempunyai pengaruh negatif terhadap kesehatan termasuk tekanan darah dan neurobehavior. Remaja pada daerah pertanian berisiko terhadap paparan pestisida OP jangka panjang melalui beberapa cara dan rute. Metode: Tiga puluh enam subjek pada daerah pertanian dan tiga puluh sembilan subjek pada daerah non pertanian diikutsertakan dalam penelitian ini. Terhadap seluruh subjek dilakukan pengukuran tekanan darah (dari duduk kemudian berdiri) dan tes neurobehavior. Untuk neurobehavior, tiga battery (waktu reaksi, digit symbol dan tepuk) dilakukan pengukuran. Dua puluh sembilan data dari masing-masing kelompok kemudian dipilih secara acak. Data yang terpilih kemudian dianalisis untuk mendapatkan beda rerata. Hasil: Fluktuasi tekanan darah lebih tinggi pada kelompok dengan paparan pestisida OP jangka panjang dibandingkan dengan kelompok tanpa paparan. Beda rerata fluktuasi sistol adalah 3.345 (95%CI; 1.226-5.464) mmHg lebih tinggi pada kelompok terpapar. Hasil yang hampir sama didapatkan pada fluktuasi diastole didapatkan 7.069 (95%CI; 4.610-9.528) mmHg lebih tinggi pada kelompok terpapar. Pada performa neurobehavior, beda rerata waktu reaksi (battery atensi) 0.180 (95%CI; 0.093-0.268) detik lebih lama pada kelompok terpapar dan beda rerata dari digit symbol (battery psikomotor) -13.759 (95%CI; -19.404-(-8.114)), lebih rendah pada kelompok terpapar. Sedangkan, jumlah tepuk (battery kecepatan motorik) tidak berbeda pada kedua kelompok. Kesimpulan: Remaja dengan paparan pestisida OP jangka panjang di daerah pertanian memiliki fluktuasi tekanan darah lebih tinggi dan performa neurobehavior lebih buruk dibandingkan kelompok tidak terpapar, kecuali kecepatan motorik. Kata kunci: Pestisida Organofosfat, Remaja, Daerah Pertanian, Perubahan Tekanan Darah, Performa Neurobehavior.
ABSTRACT BLOOD PRESSURE FLUCTUATION AND NEUROBEHAVIORAL PERFORMANCE EFFECT OF LONG TERM ORGANOPHOSPHATES (OPs) PESTICIDE EXPOSURE AMONG THE ADOLESCENTS IN AGRICULTURAL AREA Background: Organophosphates (OPs) pesticide was widely used in agricultural practice. This pesticide reported have some negative health impacts include of blood pressure and neurobehavioral. The adolescents in agricultural area are risk from long term OP pesticide exposure by multiple pathways and routes. Method: Thirty six subjects in agricultural and thirty nine subjects in non agricultural area were enrolled in this study. All the subjects had undergone blood pressure fluctuation measurement (from sitting to standing) and neurobehavioral test. For neurobehavioral performance, three batteries (reaction time, digit symbol and tapping) were measured. Twenty nine data of both groups were selected randomly. The selected data then analyzed to identify its mean difference. Results: Blood pressure fluctuation was higher in long term OPs pesticide group than non exposed group. The mean of systole fluctuation (sitting-standing) was 3.345 (95%CI; 1.226-5.464) mmHg higher in exposed group. The similar finding was found on diastole fluctuation (sitting-standing) by 7.069 (95%CI; 4.6109.528) mmHg higher in exposed group. For neurobehavioral performance, the mean of reaction time (attention battery) found 0.180 (95%CI; 0.093-0.268) second longer in exposed group and the mean difference of digit symbol (psychomotor battery) score was -13.759 (95%CI; -19.404-(-8.114)), lower score in exposed group. Meanwhile, tapping domain (motor speed battery) was not difference between two groups. Conclusion: Adolescents with long term OPs pesticide exposure in agricultural area have higher blood pressure fluctuation and poorer neurobehavioral performances than non exposed adolescents, but exception for motor speed. Key words: Organophosphate pesticide, Adolescents, Agricultural area, Blood Pressure Fluctuation, Neurobehavioral Performance.
RINGKASAN BLOOD PRESSURE FLUCTUATION AND NEUROBEHAVIORAL PERFORMANCE EFFECT OF LONG TERM ORGANOPHOSPHATES (OPs) PESTICIDE EXPOSURE AMONG THE ADOLESCENTS IN AGRICULTURAL AREA Organofosfat (OP) adalah pestisida yang paling sering digunakan dalam praktik pertanian. OP berpotensi masuk ke dalam tubuh manusia melalui beberapa cara dan rute. Masuknya pestisida kedalam tubuh manusia behubungan dengan beberapa pengaruh kesehatan termasuk sistem saraf dan integritas seluler. Populasi termasuk remaja pada daerah pertanian memiliki risiko lebih tinggi terpapar dalam jangka waktu panjang. Paparan jangka panjang ini berperan dalam penurunan performa abnormalitas tekanan darah dan neurobehavior. Secara kimia, bentuk fosforik dari substansi pestisida OP adalah penghambat ireversibel AChE. AChE ini berperan degradasi ACh untuk mencegah stimulasi neuron secara berlebihan. Penghambatan AChE oleh OP menyebabkan akumulasi ACh secara berlebihan pada synaptic cleft, yang kemudian menyebabkan efek neurotoxik. Efek neurotoksik tersebut kemudian mengganggu transmisi sinyal. Risiko tambahan OP memiliki kemampuan melewati sawar darah otak. Sifat OP tersebut berpotensi mengganggu fungsi sistem saraf pusat, yang memilki fungsi dalam koordinasi dan perilaku. OP juga mempengaruhi fungsi saraf simpatis, sebab neurotransmitter pada preganglion adalah ACh. Efek simpatis dari OP tersebut mungkin menyebabkan abnormalitas pengaturan tekanan darah. Berdasarkan latar belakang dan teori di atas, dapat dirumuskan dua hipotesis: pertama, fluktuasi tekanan darah berbeda antara remaja dengan paparan pestisida OP jangka panjang dan remaja tanpa paparan pestisida OP; kedua, performa neurobehavior (atensi, psikomotor, dan kecepatan motorik) berbeda antara remaja dengan paparan pestisida OP jangka panjang dan remaja tanpa paparan. Terdapat tiga battery digunakan untuk mengukur performa neurobehavior: waktu reaksi (atensi), digit symbol (psikomotor) dan tepuk (kecepatan motorik). Untuk membuktikan hipotesis, penelitian dilaksanakan di daerah pertanian, Banjar Dalem, Songan dan untuk pembanding dilakukan di SMP N 3 Bangli. Design penelitian adalah analitik potong lintang dengan teknik pengambilan sampel berupa purposive sampling. Tiga puluh enam pada daerah pertanian dan tiga puluh sembilan pada daerah non pertanian diikutsertakan dalam penelitian ini. Terhadap seluruh subjek dilakukan pengukuran tekanan darah (dari duduk kemudian berdiri) dan tes performa neurobehavior. Untuk performa neurobehavior, tiga battery (waktu reaksi, digit symbol dan tepuk) dilakukan pengukuran. Dua puluh sembilan data dari masing-masing kelompok kemudian dipilih secara acak. Fluktuasi tekanan darah lebih tinggi pada kelompok dengan paparan pestisida OP jangka panjang dibandingkan dengan kelompok tanpa paparan. Beda
rerata fluktuasi sistol adalah 3.345 (95%CI; 1.226-5.464) mmHg lebih tinggi pada kelompok terpapar. Hasil yang hampir sama didapatkan pada fluktuasi diastole didapatkan 7.069 (95%CI; 4.610-9.528) mmHg lebih tinggi pada kelompok terpapar. Pada performa neurobehavior, beda rerata waktu reaksi (battery atensi) 0.180 (95%CI; 0.093-0.268) detik lebih lama pada kelompok terpapar dan beda rerata dari digit symbol (battery psikomotor) -13.759 (95%CI; -19.404-(-8.114)), lebih rendah pada kelompok terpapar. Sedangkan, jumlah tepuk (battery kecepatan motorik) tidak berbeda pada kedua kelompok. Sebagai kesimpulan, Remaja dengan paparan pestisida OP jangka panjang di daerah pertanian memiliki fluktuasi tekanan darah lebih tinggi dan performa neurobehavior lebih buruk dibandingkan kelompok tidak terpapar, kecuali pada kecepatan motorik.
SUMMARY BLOOD PRESSURE FLUCTUATION AND NEUROBEHAVIORAL PERFORMANCE EFFECT OF LONG TERM ORGANOPHOSPHATES (OPs) PESTICIDE EXPOSURE AMONG THE ADOLESCENTS IN AGRICULTURAL AREA
Organophosphates (OPs) were the most common pesticide used in agricultural practice. The OPs pesticide potentially entered human body by multiple pathways and routes. This entering of pesticide to human body associated with some health impact include of nervous system and cellular integrity. Population include of adolescents in agricultural area took more risk being exposed for long time. Long term OPs exposure contributed in neurobehavioral performance deficit and blood pressure abnormality. Chemically, phosphoric form of OPs Pesticide substance is an irreversible inhibitor of AChE. The AChE is an enzyme whose function in ACh degradation to prevent excessive neuron stimulation. Inhibition of AChE by the OPs pesticide induces excessive accumulation of acetylcoline in synaptic cleft, this lead to cause neurotoxic effect. The neurotoxic effect of OPs then interfere signal transmission. The additional risk factor of OPs exposure is its ability to cross through blood brain barrier. These OPs properties were potentially interferes the central nervous system function, whose function in coordination and behavior. The OPs may also influence the sympathetic nervous system function, as its neurotransmitter in preganglion is ACh. The sympathetic effect of OPs may lead to blood pressure regulation abnormality. Base on background and theories above, two hypotheses was formulated: first, the blood pressure fluctuation is difference between adolescents with long term OPs pesticide exposure and adolescents without OPs pesticide exposure; and the second, neurobehavioral performances (attention, psychomotor, and motor speed) are different between adolescents with long term OPs pesticide exposure and adolescents without OPs pesticide exposure. Three batteries were used to measure neurobehavior performance: reaction time (attention), digit symbol (psychomotor) and tapping (motor speed). For proving the hypotheses, the research was conducted in agricultural area; Banjar Dalem, Songan and for the comparator was conducted in SMP N 3 Bangli. The study design was cross sectional analytic with purposive sampling technique. Thirty six subjects in agricultural and thirty nine subjects in non agricultural area were enrolled in this study. All the subjects undergone blood pressure measurement and neurobehavioral performance test. The blood pressure was measured in sitting and standing position to find its fluctuation. Meanwhile, the three neurobehavioral performance batteries (reaction time, digit symbol and tapping) were measured once. Twenty nine of both groups were selected randomly. The selected data then analyzed to identify its mean difference between two groups.
Blood pressure fluctuation was higher in long term OPs pesticide group than non exposed group. The mean of systole fluctuation (sitting-standing) was 3.345 (95%CI; 1.226-5.464) mmHg higher in exposed group. The similar finding was found on diastole fluctuation (sitting-standing) by 7.069 (95%CI; 4.6109.528) mmHg higher in exposed group. For neurobehavioral performance, the mean of reaction time (attention battery) found 0.180 (95%CI; 0.093-0.268) second longer in exposed group and the mean difference of digit symbol (psychomotor battery) score was -13.759 (95%CI; -19.404-(-8.114)), lower score in exposed group. Meanwhile, tapping domain (motor speed battery) was not difference between two groups. For conclusion, adolescents with long term OPs pesticide exposure in agricultural area have higher blood pressure fluctuation and poorer neurobehavioral performances than non exposed adolescents, but exception for motor speed.
TABLE OF CONTENT
COVER ............................................................................................................ i LEMBAR PENGESAHAN ............................................................................. ii LEMBAR PENETAPAN PENGUJI ............................................................... iii PREFACE ........................................................................................................ iv PERNYATAAN KEASLIAN KARYA TULIS SKRIPSI .............................. v ABSTRAK ....................................................................................................... vi ABSTRACT ..................................................................................................... vii RINGKASAN .................................................................................................. viii SUMMARY ..................................................................................................... x TABLE OF CONTENT ................................................................................... xii LIST OF TABLE ............................................................................................. xv LIST OF FIGURE ............................................................................................ xvi ABBREVIATION ............................................................................................ xvii APPENDIX ...................................................................................................... xviii CHAPTER I INTRODUCTION 1.1
Background ......................................................................................1
1.2
Research Questions ..........................................................................5
1.3
Purposes of Research .......................................................................5
1.4
Benefit of Research ..........................................................................5
CHAPTER II LITERATURE REVIEW 1.1
Organophosphate (OPs) ......................................................................7
1.1.1 Definition and Chemical Properties ...................................................7 1.1.2 Toxicokinetic and Toxicodynamic of Organophosphate ...................8 1.2
Blood Pressure Fluctuation.................................................................11
1.2.1 Physiology of Autonomic Nervous System .......................................11 1.2.2 Physiology of Blood Pressure Fluctuation due to Positional Change 12 1.2.3 The OPs Pesticide Role in Blood Pressure Fluctuation due to Positional Change 1.3
..........................................................................13
Neurobehavior ....................................................................................14
1.3.1 Physiology of Nervous System ..........................................................14 1.3.2 Neurophysiology of Muscle Contraction ..........................................17 1.3.3 Behavior Function of Nervous System ...............................................18 1.3.4 Potential Effect of OPs Pesticide in Neurobehavioral Performance ..19 CHAPTER III RESEARCH FRAMEWORK, CONCEPTUAL FRAMEWORK AND HYPOTHESIS 3.1
Thinking Framework ..........................................................................21
3.2
Conceptual Framework.......................................................................22
3.3
Hypothesis ..........................................................................................22
CHAPTER IV METHOD OF RESEARCH 4.1
Scope of Research ............................................................................23
4.1.1 Place of Research .............................................................................23 4.1.2 Duration of Research .......................................................................23 4.2
Research Design ...............................................................................23
4.3
Variable Identification......................................................................23
4.4
Operational Definition of Variable ..................................................24
4.5
Research Subject ..............................................................................26
4.6
Inclusion and Exclusion Criteria ......................................................26
4.6.1 Inclusion Criteria ..............................................................................26 4.6.2 Exclusion Criteria.............................................................................26 4.7
Sample ..............................................................................................26
4.8
Research Instrument .........................................................................27
4.9
Research Protocol .............................................................................28
4.10
Data Collection .................................................................................28
4.11
Data Analysis and Tabulation ..........................................................29
CHAPTER V RESULT AND DISCUSSION 5.1
Data Collection .................................................................................30
5.2
Characteristic of Sample ..................................................................30
5.3
Data Representation .........................................................................31
5.3.1 Blood Pressure Fluctuation ..............................................................31 5.3.2 Neurobehavioral Performance..........................................................33 5.4
Data Analysis and Discussion ..........................................................35
5.4.1 Blood Pressure Fluctuation ..............................................................35 5.4.2 Neurobehavioral Performance..........................................................39 CHAPTER VI CONCLUSION...........................................................................46 6.1
Conclusion .......................................................................................46
6.2
Suggestions.......................................................................................46
REFERENCE
LIST OF TABLE
Page Table 5.1 Characteristic of Sample ................................................................... 30 Table 5.2 Mean difference of systole fluctuation (sitting-standing) between Long Term OPs Pesticide Exposure and Non Exposure .................... 35 Table 5.3 Mean difference of diastole fluctuation (sitting-standing) between Long Term OPs Pesticide Exposure and Non Exposure .................... 36 Table 5.4 Mean difference of reaction time between Long Term OPs Pesticide Exposure and Non Exposure............................................... 39 Table 5.5 Mean difference of Digit Symbol Score between Long Term OPs Pesticide Exposure and Non Exposure .............................................. 40 Table 5.6 Mean difference of Hand Tapping between Long Term OPs Pesticide Exposure and Non Exposure............................................... 41
LIST OF FIGURE
Page Figure 2.1 General structure of organophosphate (OP) ....................................... 7 Figure 2.2 The structure of toxic OP warfare agents ........................................... 7 Figure 2.3 The structures of methyl-parathion and methyl-paraoxon ................. 8 Figure 2.4 Oxidation and Hydrolyzation of Chlorpyrifos ................................... 10 Figure 2.5 The binding of OP to the active site of AChE.................................... 10 Figure 2.6 General structure of Neuron ............................................................... 15 Figure 2.7 Neurotransmission process in synapse ............................................... 16 Figure 2.8 Excitation-contraction coupling of muscle contraction ..................... 18 Figure 3.1 Conceptual Framework ...................................................................... 22 Figure 5.1 Box plot of Systole Fluctuation (sitting-standing .............................. 32 Figure 5.2 Box plot of Diastole Fluctuation (sitting-standing). .......................... 32 Figure 5.3 Box plot of Reaction Time base on status of OPs Pesticide Exposure ............................................................................................. 33 Figure 5.4 Box plot of digit symbol score base on status of OPs Pesticide Exposure ............................................................................................. 34 Figure 5.5 Box plot of hand tapping base on status of OPs Pesticide Exposure . 35
ABBREVIATION OPs
= Organophosphates
OP
= Organophosphate
ACh
= Acetylcholine
AChE
= Acetylcholine Esterase
LIST OF APPENDIX Research Schedule Lembar Persetujuan Responden (Informed Consent) Lembar Pengumpulan Data (Data Collection Sheet) SPSS Based Data
CHAPTER I INTRODUCTION
1.1 Background Indonesia is a country with dense population in world. According to Badan Pusat Statistik on census 2010, Indonesian population was 237 millions, this brought Indonesia as the fourth most number population in the world. Among this number, 26.67% were adolescents; age 10-24 years, in addition adolescents was rendered 60.06% of the labor (BKKBN, 2011).
The demographic showed that
approximately 34% of populations were working on Agriculture. Especially in Bali, the agricultural populations contributed 1.64% of all Indonesian agriculture sector (BPS, 2010). According to oxford dictionary, Agriculture is the science or practice of farming, including cultivation of the soil for the growing of crops and the rearing of animals to provide food, wool and other products. The end of agricultural process especially in crops is the harvest. The harvest is influenced by many factors include of climate, weather, pest, and many others. When the harvest was failed, farmers tend to judge that the pest was the main causal of harvest failure. This perception made the utilization of pesticide have been increased over the time. About 20-30% of cost production among vegetable farmers used pesticide, this became second most expenditure of cost production (Ameriana, 2008). In Thailand, 54.4% of agriculture areas reported using pesticides, of which 45.9% used chemical (Saowanee et al, 2012). 1
There are many kinds of pesticide, but the organophosphate was most widely used in agricultural practice. In United State, approximately 5.2 million pounds of pesticide was used in 2006, but only 1% of them reached lethal doses in pest targeted (Hernendez, 2012). Another study reported that there were 15 million kg OPs pesticide used in United State in 2007. Then, 1.6 million kg of Organophosphates (OPs) were used in 2008 (Bouchard et al, 2011). Pesticides which used were varying according to kind of pests. The kind of pests was difference on each kind of cultivate, so this mean the number of cultivate variation will comparable to type of the pesticide used. In multicultural there been increasing type and concentrate of pesticide utilization every year. This was due to variety of cultivation, pesticide resistant and farming along the year. Moreover, pesticides resistant compel the farmer to substitute with more potent pesticide. The OPs was a kind of pesticide that widely used in agricultural practice which had been successfully to prevent harmful of pest. But, most of them may affect non-target organisms such as human (Saowanee et al, 2012). Exposure to pesticide of human is through multiple pathways (e.g. food, drinking, residential, and occupational) and routes (e.g. oral, dermal, and inhalation). The risk hazard of pesticide depend on number of routes and pathways, frequency of exposure, duration, and chemical category of pesticide (Hernendez, 2012). Directly, it can enter human body through the contaminated air while and after pesticide’s syringing, in which commonly occurred among the farmer and population around syringing. Meanwhile the consumer could be intoxicated indirectly through crops’ product. Indirect way, the population around the cultivation may also consume
contaminated water beside the product. So, that means that populations in agriculture area have multiply potent pesticide exposed compare to non-agricultural area. The additional hazard of pesticide is increasing the concentrations, frequency, substitution to more potential and mixture some pesticide over the time (Ameriana, 2008). Exposed or consuming pesticide contaminated products can cause negative effects on human health. Studies had been explored that pesticide affect the endocrine system, metabolism mainly glucose and lipid, neural degeneration, reproductive and respiratory. The importance that has been noted is its effect on neural and endocrine development during critical period of early life (Eskenazi et al, 2007; Androutsopoulos et al, 2013). The OPs pesticide’s mechanism of action on neural through inhibition of Acetilcolinesterase (AChE) resulting in accumulation of Acetylcolin, in turn induce excessive muscarinic and nicotinic stimulation. Inhibition of AChE, disrupts cell replication, synaptogenesis and axonogenesis leading neuronal dysfunction and excitotoxicity. According to the age, children and fetuses have lower level of paraoxonase or chlorpyrifos-oxonase (detoxifying enzyme), so this age more vulnerable to these exposure. Another potential risk of pesticide is its ability to cross through placenta and blood brain barrier (Eskenazi et al, 2007; Androutsopoulos et al, 2013). Another possible side effect of OPs pesticide is its effect on autonomic nervous system. As known, Acetylcholine also found as neurotransmitter of preganglionic sympathetic nervous and postganglionic for sweet gland only (Baehr et al, 2005). This sympathetic nervous has function in modulation of blood pressure,
especially to compensate blood pressure change when body position is turning up from lying. So, OPs pesticide exposed potentially cause disturbing sympathetic nervous in compensating blood pressure. Systole and diastole fluctuation from sitting to standing position may important as predictor of orthostatic hypotension, even epidemiologically orthostatic hypotension rarely occurred in adolescents. The neurotoxicities that may be caused by OPs are Cholinergic Syndrome, Intermediate syndrome, Organophosphate-induce delay polyneuropathy (OPIDP) and chronic organophosphate-induce neuropsychiatric disorder (COIND). Other than that, World Health Organization (WHO) reported that about 1 million accidental and 2 million suicidal poisoning with OPs insecticide were occurred per year, with more than three hundred thousand fatalities. Moreover, medical management is difficult with case fatality commonly more than 15% (Jokanovic et al, 2010). These neural influences of OPs also associated to neurobehavioral performances both in acute case or chronically (Olson, 2015; Harari et al., 2010; Kamel et al., 2003) . As mention above, the utilization of pesticides were high among the agriculture. Along with this, there also many negative effect of OPs in human health. The research of this issue had been conducted among the prenatal, children and adult refer to pesticide exposure, but few were assessed in adolescence. Most of studies were conducted in acute intoxication and its long term effect. There were limited data about long (chronic) term intoxication of OPs effect. Moreover, almost all of the data that published were found in foreign studies, just limited data were provided from Indonesian studies. Therefore, this research would like to asses effect of long term of low level OPs pesticide exposure in neurobehavior among the adolescents in
agricultural area. This is important in order to provide a data which can be used as preliminary study of future research, or reference of program building in establishing heath agriculture. 1.2
Research Questions
Based on background above, the Research Questions can be formulated as below: 1.2.1 Is the blood pressure fluctuation (from sitting to standing) difference between adolescents with long term OPs pesticide exposure and adolescents without OPs pesticide exposure? 1.2.2 Are neurobehavioral performances (attention, psychomotor and motor speed) different between adolescents with long term OPs pesticide exposure and adolescents without OPs pesticide exposure? 1.3
Purposes of Research
1.2.1 To know the difference of blood pressure fluctuation (from sitting to standing) between adolescents with long term OPs pesticide exposure and adolescents without OPs pesticide exposure. 1.2.2 To
know
the
different
of
neurobehavioral
performance
(attention,
psychomotor and motor speed) between adolescents with long term OPs pesticide exposure and adolescents without OPs pesticide exposure. 1.4
Benefits of Research
1.4.1 Benefit for Researcher Enhance the knowledge about effect of OPs in blood pressure fluctuation (from sitting to standing) and neurobehavioral performances (attention, psychomotor and motor speed) in adolescents.
1.4.2 Benefits in Science a.
Give a contribution in science about effect of long term OPs exposure in blood pressure
fluctuation
(from
sitting
to
standing)
and
neurobehavioral
performances (attention, psychomotor and motor function) among adolescents. b.
As preliminary study for other studies on the future.
1.4.3 Benefit for health service and regulation a.
Give a description about effects of OPs pesticide in blood pressure fluctuation (from sitting to standing) and neurobehavioral as a basic concept of underlying problems that affect blood pressure and neurobehavioral functions.
b.
Give description of agriculture’s condition and health related, so better program can be developed in order to build health agriculture.
