UNIVERSITI PUTRA MALAYSIA

RELATIONSHIP BETWEEN SERUM IgG LEVEL, FRACTIONAL

EXHALED NITRIC OXIDE AND MICROBIAL CONTAMINATION IN METALWORKING FLUIDS AMONG MACHINISTS IN NILAI,

NEGERI SEMBILAN, MALAYSIA

NURUL MAIZURA BINTI HASHIM

FPSK(M) 2017 56

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RELATIONSHIP BETWEEN SERUM IgG LEVEL, FRACTIONAL EXHALED

NITRIC OXIDE AND MICROBIAL CONTAMINATION IN

METALWORKING FLUIDS AMONG MACHINISTS IN NILAI,

NEGERI SEMBILAN, MALAYSIA

By

NURUL MAIZURA BINTI HASHIM

Thesis Submitted to the School of Graduate Studies, Universiti Putra Malaysia, in

Fulfilment of the Requirements for the Degree of Master of Science

December 2016

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All material contained within the thesis, including without limitation text, logos, icons,

photographs and all other artwork, is copyright material of Universiti Putra Malaysia

unless otherwise stated. Use may be made of any material contained within the thesis for

non-commercial purposes from the copyright holder. Commercial use of material may

only be made with the express, prior, written permission of Universiti Putra Malaysia.

Copyright © Universiti Putra Malaysia

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Abstract of thesis presented to the Senate of Universiti Putra Malaysia in fulfilment of

the requirement for the degree of Master of Science

RELATIONSHIP BETWEEN SERUM IgG LEVEL, FRACTIONAL EXHALED

NITRIC OXIDE AND MICROBIAL CONTAMINATION IN

METALWORKING FLUIDS AMONG MACHINISTS IN NILAI,

NEGERI SEMBILAN, MALAYSIA

By

NURUL MAIZURA BINTI HASHIM

December 2016

Chairman : Professor Zailina Hashim, PhD

Faculty : Medicine and Health Sciences

Introduction: Metalworking fluids (MWFs) are commonly used in machining industry

during metal working process such as cutting, turning, milling, drilling and grinding.

Water based metalworking fluids (MWFs) are commonly used in machining industries

and are excellent media for microorganism growth. Machining’s workers are most

exposed to the contaminant of metalworking. Problem Statement: Machining industry

is one of the industries in Malaysia that are rapidly growth. Soluble metalworking

fluids (MWFs) are commonly used by machining industry. These fluids represent a

high potential for health risk due to high water content present in the emulsion which is

excellent for micro-organism growth. Respiratory problem and skin problem may be

implicated by the microbial contaminants exposure of metalworking fluids (MWFs).

Upper airway inflammation was a common problem among machinists and it is

reported that, about 39% of the workers exposed to MWFs had airway symptoms.

MWFs exposure containing a mixture of reactive and pro-inflammatory agents may

induce a toxic response in the upper cell-linin, resulting in decreased formation of

normally expressed immune defence protein. Objective: To study the relationships

between serum IgG levels and airway inflammation with the microbial exposure among

MWFs workers. Methodology: This cross sectional study was carried out on 138

machining workers exposed to MWF. Background, working, health and resedential

information of respodents were collected by a set of questionaire adapted from

American Thoracic Society (ATS-DLD-78). Two ml blood were drawn from the

cubital to be tested for the level of total and specific IgG antibody in blood. The

workers’ FeNO were measured using NIOX-MINO instrumentation. The microbial

assessments were carried out on the MWF bulk samples and the aerosol in the work

environment. DUO SAS SUPER 360TM sampler was used to sample the bacteria and

fungi in the air. The data were analysed using the SPSS Version 22.0. Result and

Discussion: This study found that, the mean value for the environmental bacteria and

fungal in all work sections were 285.83cfu/m3 and 231.2cfu/m3 respectively. Whereas,

the means for microbial contamination in bulk samples were 37916.7 cfu/ml3 (bacteria)

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and 38833.3 cfu/ml3 (fungal) respectively. The mean of the IgG in all work sections

was 13.79 g/litre. The environmental bacteria levels has a significant correlation with

the total IgG antibodies levels (p=0.003). There were also a significant relationship

between BMI (p=0.044), work duration (p=0.014), smoking (p=0.014) and

environmental contaminants (0.049) with the total of IgG.levels Findings also showed

significantly difference in the FeNO levels of workers from various work sections

(p=0.01). From the multivariate statistics, there were also significant relationships

between the high FeNO with their closeness between machines (p=0.03), higher

number of machines (p=0.02), high environmental bacteria colonies (p=0.04), longer

employment years (p=<0.001) and frequent reporting of respiratory symptom such as

cough (p=0.03). Conclusion: There were significant correlations between the total IgG

antibodies levels with the microbial contaminants of metalworking fluids in metal

working process. Besides, there were also significant relationships between work

duration, smoking, BMI and environmental contaminants with the total IgG.levels.

Risk factors from the workplace such as the number of machines, closeness between

machines and high environmental bacteria colonies and longer employment years had

significant relationships with the airway inflammation (FeNO). Exposure to MWF also

resulted in significantly frequent cough symptom.

Keywords: Metalworkings fluids, IgG Antibodies, Microbial Contaminants, Airway

Inflammation and Fractional Exhaled Nitric Oxide (FeNO)

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Abstrak tesis yang dikemukakan kepada Senat Universiti Putra Malaysia sebagai

memenuhi keperluan untuk ijazah Master Sains

HUBUNGAN ANTARA SERUM IgG DAN KERADANGAN SALUR

PERNAFASAN SEBAGAI PENENTU PENDEDAHAN MIKROB DALAM

BENDALIR KERJA LOGAM ANTARA PEKERJA PEMESINAN DI NILAI,

NEGERI SEMBILAN, MALAYSIA

Oleh

NURUL MAIZURA BINTI HASHIM

Disember 2016

Pengerusi

Fakulti

: Professor Zailina Hashim, PhD: Perubatan dan Sains Kesihatan

Pengenalan: Bendalir kerja logam (MWFs) yang biasa digunakan dalam industri

pemesinan semasa proses kerja logam seperti memotong, membelok, pengilangan,

penggerudian dan pengisaran. Bendalir kerja logam (MWFs) yang berasaskan air biasa

digunakan dalam industri pemesinan merupakan media yang sangat baik bagi

pertumbuhan mikroorganisma. Pekerja pemesinan ini adalah yang paling terdedah

kepada bahan cemar logam. Pernyataan Masalah: Industri pemesinan adalah salah

satu industri di Malaysia yang pesat pertumbuhan. cecair logam larut (MWFs) yang

biasa digunakan oleh industri pemesinan. cecair ini mewakili potensi yang tinggi untuk

risiko kesihatan kerana kandungan air yang tinggi di dalam emulsi yang sangat baik

untuk pertumbuhan mikro-organisma. masalah pernafasan dan masalah kulit mana

yang berkaitan dengan pendedahan pencemaran mikrob cecair logam (MWFs). Upper

keradangan saluran udara adalah masalah biasa di kalangan machinists dan ia

dilaporkan bahawa, kira-kira 39% daripada pekerja yang terdedah kepada MWFs

mempunyai gejala saluran udara. pendedahan MWFs mengandungi campuran ejen

reaktif dan pro-radang boleh menyebabkan tindak balas toksik di atas sel-linin,

menyebabkan pembentukan penurunan biasanya dinyatakan protein pertahanan imun

Objektif: Untuk mengkaji hubungan antara tahap serum IgG dan keradangan saluran

pernafasan dengan pendedahan mikrob dalam kalangan pekerja MWFs. Metodologi:

Kajian irisan lintang telah dijalankan ke atas 138 pekerja pemesinan yang terdedah

kepada MWFs. Maklumat latar belakang, pekerjaan, kesihatan dan kediaman respoden

telah dikumpulkan dalam satu set soal selidik yang diadaptasi daripada Persatuan

Thoracic Amerika (ATS-DLD-78). Dua ml darah telah diambil daripada cubital

respondan untuk menguji tahap jumlah antibodi IgG dalam darah. Pecahan hembusan

Nitrik Oksida (Feno) pekerja diukur menggunakan instrumen NIOX-MINO. Penilaian

mikrob telah dijalankan ke atas sampel MWF di setiap mesin dan aerosol dalam

persekitaran kerja. Intrumen DUO SAS SUPER 360TM telah digunakan untuk

persampelan bakteria dan kulat di udara. Data telah dianalisis dengan menggunakan

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perisian SPSS Versi 22.0. Keputusan dan Perbincangan: Kajian ini mendapati

bahawa, nilai minima bagi bakteria alam sekitar dan kulat dalam semua bahagian kerja

adalah 285.83 cfu/m3 dan 231.2 cfu/m3. Manakala pencemaran mikrob dalam sampel

MWFs adalah 37.9167 cfu/ml3 (bakteria) dan 38.8333 cfu/ml3 (kulat). Purata bagi

tahap IgG dalam semua bahagian kerja adalah 13.79 g/liter. Tahap Bakteria di dalam

persekitaran mempunyai hubungan yang signifikan dengan jumlah IgG antibodi

(p=0.003). Terdapat juga hubungan yang signifikan antara BMI (p=0.044), tempoh

kerja (p=0.014), merokok (p=0.014) dan microb di persekitar (0,049) dengan tahap IgG

responden. Dapatan kajian juga menunjukkan perbezaan dalam tahap Feno pekerja dari

pelbagai bahagian kerja (p=0.01). Daripada statistik multivariate, terdapat juga

hubungan yang signifikan antara Feno yang tinggi dengan jarak antara mesin (p=0.03),

bilangan mesin yang lebih tinggi (p=0.02), microb persekitaran yang tinggi (p=0.04),

pengalaman bekerja yang lama (p=<0.001) dan laporan gejala pernafasan seperti batuk

(p=0.03). Conclusion: Terdapat hubungan signifikan antara jumlah antibodi IgG

dengan microb di dalam sampel berdalir kerja logam dalam proses kerja logam. Selain

itu, terdapat juga hubungan yang signifikan di antara tempoh kerja, merokok, BMI dan

pencemaran microb di persekitaran dengan tahap IgG. Faktor-faktor risiko dari tempat

kerja seperti bilangan mesin, jarak antara mesin dan pencemaran microb di persekitaran

yang tinggi dan tahun pekerjaan juga mempunyai hubungan yang signifikan dengan

keradangan saluran udara(Feno). Pendedahan kepada MWFs juga menyebabkan gejala

batuk ketara.

Kata Kunci: Bendalir Kerja Logam, Antibodi IgG, Pencemaran Mikrob, Keradangan

Salur Pernafasan dan Pecahan hembusan Nitrik Oksida (Feno)

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ACKNOWLEDGEMENTS

In the name of Allah, the Most Gracious and the Most Merciful. Alhamdulillah, all

praises to Allah for the strengths and His blessing in completing this thesis. I would

like to express my deepest gratitude and appreciation to every person who gave me

strength and ideas to complete this report. Special appreciation goes to my supervisor,

Prof. Dr. Zailina Hashim, for her guidance, encouragement and assistance throughout

this whole project. Her invaluable help of constructive comments and suggestion

throughout the experimental and thesis works have contributed to the success of this

research.

I would like to express my deeply and highest appreciation to the management of the

study factory in Nilai and also respondents in this study for their help, cooperation and

support throughout this study. My gratitude also goes to all my great research team for

their endless support throughout this study.

Next on the list, my deepest gratitude goes to my beloved parent, Mr. Hashim Harun

and Mrs. Normah Kussin for their constant love and immeasurable sacrifice. Without

them besides me, I would never have enjoyed so many opportunities in my entire life.

Last but not least, thanks to my husband, Abdul Rahman and our beloved daughter,

Aish Alisha for their endless love, prayers and encouragement. To those who indirectly

contributed in this research, your kindness means a lot to me.

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This thesis was submitted to the Senate of Universiti Putra Malaysia and has been

accepted as fulfilment of the requirement for the degree of Master of Science. The

members of the Supervisory Committee were as follows:

Zailina Hashim, PhD

Professor

Faculty of Medicine and Health Sciences

Universiti Putra Malaysia

(Chairman)

Rukman Awang Hamat, PhD

Associate Professor

Faculty of Medicine and Health Sciences

Universiti Putra Malaysia

(Member)

Hayati Kadir, PhD

Senior Lecturer

Faculty of Medicine and Health Sciences

Universiti Putra Malaysia

(Member)

__________________________

ROBIAH BINTI YUNUS, PhD

Professor and Dean

School of Graduate Studies

Universiti Putra Malaysia

Date:

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Declaration by graduate student

I hereby confirm that:

this thesis is my original work;

quotations, illustrations and citations have been duly referenced;

this thesis has not been submitted previously or concurrently for any other degree

at any other institutions;

intellectual property from the thesis and copyright of thesis are fully-owned by

Universiti Putra Malaysia, as according to the Universiti Putra Malaysia

(Research) Rules 2012;

written permission must be obtained from supervisor and the office of Deputy

Vice-Chancellor (Research and Innovation) before thesis is published (in the form

of written, printed or in electronic form) including books, journals, modules,

proceedings, popular writings, seminar papers, manuscripts, posters, reports,

lecture notes, learning modules or any other materials as stated in the Universiti

Putra Malaysia (Research) Rules 2012;

there is no plagiarism or data falsification/fabrication in the thesis, and scholarly

integrity is upheld as according to the Universiti Putra Malaysia (Graduate

Studies) Rules 2003 (Revision 2012-2013) and the Universiti Putra Malaysia

(Research) Rules 2012. The thesis has undergone plagiarism detection software.

Signature: ________________________ Date: __________________

Name and Matric No.: Nurul Maizura Binti Hashim (GS41438)

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Declaration by Members of Supervisory Committee

This is to confirm that:

the research conducted and the writing of this thesis was under our supervision;

supervision responsibilities as stated in the Universiti Putra Malaysia (Graduate

Studies) Rules 2003 (Revision 2012-2013) are adhered to.

Signature:

Name of Chairman of

Supervisory

Committee:

Signature:

Name of Member of

Supervisory

Committee:

Signature:

Name of Member of

Supervisory

Committee:

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TABLE OF CONTENTS

Page

ABSTRACT i

ABSTRAK iii

ACKNOWLEDGEMENTS v

APPROVAL vi

DECLARATION viii

LIST OF TABLES xiv

LIST OF FIGURES xv

LIST OF ABBREVIATIONS xvi

CHAPTER

1 INTRODUCTION 1

1.1 Introduction 1

1.2 Problem statement 3

1.3 Research justification 5

1.4 Study variables 5

1.5 Conceptual framework 5

1.6 Research objective 8

1.7 Research hypothesis 8

2 LITERATURE REVIEW 9

2.1 Metalworking fluids (MWFs) 9

2.1.1 Metalworking fluids (MWFs) additives 10

2.2 Health effects of metalworking fluids (MWFs) 11

2.2.1 Respiratory symptoms 11

2.2.2 Skin symptoms 12

2.3 Microbial contamination in MWFs 14

2.3.1 Species of microbial contaminants in MWFs 15

2.3.2 Infectious disease caused by microbial agent 15

2.4 Human immune system 16

2.4.1 Immunoglobulin g (IgG) 17

2.5 Fractional exhaled nitric oxide 18

2.5.1 Principal and mechanisms of nitric oxide 18

2.6 Airway Inflammation 20

2.6.1 Mechanism of airway inflammation 21

2.6.2 Airway inflammation among MWFs workers 22

3 MATERIALS AND METHODS / METHODOLOGY 24

3.1 Study location 24

3.1.1 Workplace information 25

3.1.2 Work process 27

3.2 Study design 29

3.3 Sampling 29

3.3.1 Sampling population 29

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3.3.2 Sampling frame 29

3.3.3 Sampling unit 30

3.3.4 Sampling method 30

3.3.5 Study sample 30

3.4 Study instrumentation 31

3.4.1 DUO SAS SUOER 360™ 31

3.4.2 NIOX-MINO device 32

3.4.3 Questionnaire 33

3.4.4 TANITA® digital scale 33

3.4.5 Body meter SECA® 208 33

3.4.6 Roche Cobas C501 analyser (automated

chemistry analyser)

34

3.4.7 ELISA kit 34

3.4.8 Analytical Profile Index (API) 35

3.5 Data collection procedure 35

3.5.1 Pilot study 35

3.5.2 Face-to-face interview 35

3.5.3 Microbial air sampling 36

3.5.4 MWFs sampling 36

3.5.5 Blood collection 37

3.5.6 Measurement of FeNO 37

3.5.7 Microorganism identification 38

3.5.8 Microorganism speciation using API 40

3.5.9 Detection of IgG for specific bacteria by using

ELISA kit

45

3.5.10 Analysis of total IgG level in blood by using

automated chemistry analyser (Roche Cobas C501)47

3.6 48

3.7

Data analysis

Quality control 48

3.7.1 Questionnaire 48

3.7.2 Microbial air sampling 48

3.7.3 IgG analysis in blood 48

3.7.4 Fractional nitric oxide measurements 49

3.7.5 Microbial analysis 49

3.8 Study ethics 49

4 RESULTS AND DISCUSSION 50

4.1 Socio demographic characteristic 50

4.2 Residential information 50

4.3 Employment information 52

4.4 Workplace information 54

4.5 Microbial contamination levels and species in various

work section

54

4.5.1 Microbial contaminations levels in various

section

54

4.5.2 Microbial contamination species in various

work section

55

4.6 Distribution of total and specific serum IgG levels, FeNo

levels, respiratory and skin symptoms of the respondents

in various work section

57

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4.6.1 Total serum igg level in blood at various work

section

57

4.6.2 IgG antibodies in the serum of respondents

against specific microorganism at various work

section

58

4.6.3 FeNo level of respondents at various work

section

59

4.6.4 Reported health symptoms information 60

4.7 Correlation between serum IgG and FeNO levels with

microbial levels

61

4.7.1 Correlation between serum IgG levels with

microbial levels 61

4.7.2 Correlation between FeNo levels with

microbial levels 62

4.8 The relationship between microbial levels with workplace

characteristics. 62

4.9 Relationship between health outcomes with individual,

residential and workplace characteristics of the

respondents and microbial levels.

64

4.9.1 The relationship between total serum IgG with

individual, residential and workplace

characteristics of respondents

64

4.9.2 Relationship between specific IgG antibodies

level against specific microorganisms of the

respondents with individual, residential,

workplace characteristics and microbial levels.

66

4.9.3 Relationship between FeNo levels with

individual, residential, workplace

characteristics and microbial levels.

70

4.10 Association between reported health symptoms with the

IgG antibodies level against specific microorganism.

70

4.11 Relationship between reported health symptoms 74

5

information with total serum IgG and FeNo levels.

DISCUSSION 75

5.1 Subject and method 75

5.2 Individual characteristics of the respondents 75

5.3 Microbial contaminants levels in different work section 76

5.4 Species of microbial contaminants in different work

sections.

77

5.5 Total serum igg level in blood at various work section 79

5.6 Specific serum IgG level in blood at different work

section

79

5.7 FeNo level of respondents from various work section 80

5.8 Correlation between the total serum IgG levels of

respondents from various work section

80

5.9 Correlation between the FeNo level with environmental

and MWF microbial contaminants

80

5.10 The relationship between total serum IgG level with

individual, residential, workplace characteristics and

microbial levels

81

5.11 The relationship between FeNo levels with individual, 82

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residential, workplace characteristics and microbial

5.12 The relationship between the health symptoms with the

total serum IgG and FeNo levels 82

6 SUMMARY, CONCLUSION AND RECOMMENDATIONS

FOR FUTURE RESEARCH

84

REFERENCES 88

APPENDICES 97

BIODATA OF STUDENT 110

LIST OF PUBLICATIONS 111

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LIST OF TABLES

Table Page

2.1 Examples of metalworking fluids additives 10

3.1 The list of MWF and chemical used in each section 28

4.1 Individual characteristics of the respondents. 51

4.2 Residential information of the respondents. 52

4.3 Respondents’ work information 53

4.4 Information on the workplace 54

4.5 Microbial contaminants levels in different work section 55

4.6 Microbial species in different work sections. 56

4.7 Distribution of serum IgG Level in Blood at Various Work Sections 57

4.8 Distribution of the IgG Antibodies Level against

Pseudomonas aeruginosa of the Respondents.

58

4.9 Distribution of the IgG antibodies level against Klebsiella

pneumoniae of the respondents.

58

4.10 Distribution of the IgG antibodies level against E. coli of the

respondents.

59

4.11 Distribution of the IgG antibodies Level against Candida albicans of

the respondents

59

4.12 Distribution of FeNO levels of respondents at various work sections 60

4.13 Prevalence of health symptoms reported by respondents 61

4.14 Correlation between the serum IgG level with environmental and

fluid microbial contaminants

62

4.15 Correlation between the FeNO Level with environmental and MWFs

microbial contaminants

62

4.16 The relationship between microbial levels with workplace

characteristics.

63

4.17 The relationship between total serum IgG with individual and

workplace characteristics of respondents

65

4.18 The relationship between total serum IgG with individual and

workplace characteristics of respondents

66

4.19 Relationship between specific IgG antibodies level against specific

microorganisms characteristics

67

4.20 Relationship between specific IgG antibodies level against specific

microorganisms of the respondents with residential characteristics.

68

4.21 Relationship between specific IgG antibodies level against specific

microorganisms of the respondents with workplace characteristics

and microbial levels

69

4.22 Relationship between FeNO levels with individual and residential

characteristics.

71

4.23 Relationship between FeNO levels with workplace characteristics

and microbial levels.

72

4.24 Association between the IgG antibodies level against specific

microorganism with reported health symptoms.

73

4.25 The relationship between reported health symptoms with total serum

IgG and FeNO levels.

74

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LIST OF FIGURES

Figure Page

1.1 Conceptual framework 7

2.1 Regulation of inducible nitric oxide synthase (iNOS) expression in

human airway proposed by Alvin and Malonovschi

19

2.2 The different between normal and inflamed lung 20

2.3 Schematic diagram of the role of airway smooth muscle in airway

inflammation

22

3.1 Study Location at Kawasan Perindustrian Nilai, Nilai, Negeri

Sembilan

24

3.2 Example of Bearings 25

3.3 Plant Layout for Each Section 26

3.4 Flowchart for the work process of bearing manufacturing 27

3.5 Sampling Unit 28

3.6 The Duo SAS Super 360™ 32

3.7 NIOX-MINO Monitor 32

3.8 Tanita Digital Body Fat Scales 33

3.9 SECA Bodymeter 208 34

3.10 Roche Cobas C501 Chemistry 34

3.11 Flowchart of microorganism identification process 39

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LIST OF ABBREVIATIONS

BMI Body Mass Index

CFU Colony Forming Unit

DGBB Deep Groove Ball Bearing

eNos Endothelial Nitric Oxide Synthase

FeNo Fractional Exhaled Nitric Oxide

HVAC Heating, Ventilation, And Air Conditioning.

ICS Inhaled Corticosteroid Therapy

iNOS Inducible Nitric Oxide Synthase

IgG Immunoglobulin G

LPS Lipopolysaccharide

LSR Large Size Roller

MBL Mannose Binding Lectin

MSDS Material Safety Data Sheet

MWFs Metalworking Fluids

nNOS Neuronal nitric oxide synthase

NO Nitric Oxide

NOS Nitric Oxide System

Ppb Part Per Billion

PPE Personal Protective Equipment

SABB Self-Aligning Ball Bearing

SRB Spherical Roller Bearing

TH T-helper

X2 Chi Square

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CHAPTER 1

INTRODUCTION

1.1 Background of Study

Metalworking fluids (MWFs) are commonly used in machining industry during metal

working process such as cutting, turning, milling, drilling and grinding. These fluids

wer3e used extensively as industrial lubricants to provide lubricate cool metalworking

operation by reducing friction at tool-work piece interfaces and carrying away heat.

MWFs are also frequently known as coolant, lubricants, machining fluids and cutting

oil (NIOSH, 2011). MWFs generally comprised four major categories which are

straight oil, soluble oil, semi-synthetic fluids and synthetic fluids. Straight oil contain

of highly refined petroleum, marine, vegetable, animal or synthetic oil and not to be

diluted with water. Soluble oil is the combination of highly refined lubricant-based oil

and emulsifiers which will be diluted with water. Semi-synthetic fluids contain lower

amount of highly refined lubricant-based oil and is water soluble .Synthetic fluids is

water soluble and contain no petroleum oil (NIOSH, 1998). All of these MWFs are

water soluble except for straight oil.

MWFs are usually contains a wide range of additives, such as biocides, surfactants,

anti-oxidants, corrosion inhibitor, emulsifiers and stabilizers. Various chemical

additives are formulated into MWFs in order to achieve specific performance

requirements. Each of these additives has specific function and its own negative effects

to the worker’s health (Fornander, 2013).

Since the most frequently used MWFs in machining industry are water-based type, the

primary concern is the presence of contaminants that encourage the growth of bacteria

and fungi. The fluids contain hydrocarbon, organic substrate, phosphorus, nitrogen and

water which are conducive for microbial growth. Biological agents present in the

MWFs liquids are emitted in the formed of droplet bioaerosols during a rapid rotation

of the working metal tools which are inhaled by machine operator and causing adverse

health effects mainly on respiratory system (Cyprowski et al., 2007).

Exposures to MWFs were associated to various health diseases such as cancer,

respiratory outcome and skin disease (Park et al., 2009). Dermatitis is the most

common complaint associated with MWFs. Respiratory effects such as upper

respiratory irritation, asthma and hypersensitive pneumonitis (HP) are caused by

exposure to diluted MWFs, microbial contaminants and chemical contaminants of the

fluids (Park et al., 2009).

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Based on a National Occupational Exposure Survey (NOES) by the National Safety

and Health, it is estimated that 1.2 million workers are potentially exposed to MWFs

(NIOSH, 1983). Workers were exposed to the MWFs by inhalation of the diluted fluids

mist (aerosol) or skin absorption of fluids through contact with the MWFs during the

handling with the workpieces coated with fluids (NIOSH, 1998).

Other chemical constituents may also presence in MWFs during their recirculation such

as debris, dust, metal swarf, metal fines, hydraulic oil, bacteria and fungi (Burton et al.,

2012). The MWFs are still easily contaminated by microbes even after the adding of

biocides into the fluids as a treatment and remain in the tanks (Mattsby-Baltzer et al.,

1989). The breakdown product of biocides in the MWFs may serve as nutrients for

microbial growth. The common contaminants in MWFs are the Gram-negative bacteria

(Bakalova et al., 2007).

There is very few biomarkers of exposure or dose have been identified. IgG molecules

are composed of two light chain (kappa or lamda) and two gamma heavy chain.

Approximately 80% of serum immunoglobulin is IgG and its main task is to defence

our body against microorganism. IgG antibodies in serum have been suggested as an

indirect marker of exposure of fungi (Burell and Rylander, 1981; Eduard et al., 1992).

IgG antibodies serve as excellent indicator and tool in assessing the exposure to

microbial contaminants. There is significant elevation of IgG antibodies response to

bacteria antigen (Laitinen et al., 1999).

Based on National Safety and Health (NIOSH), there is no recommended or specific

limit for bacterial and fungal concentration in contaminated MWFs due to limited and

insufficient health data. Thus, management programme of MWFs is conducted in order

to protect workers. However, not all of the control measures are successful in

eliminating the microbial contaminants. For example, addition of biocides in the

MWFs may result in the emergence of other biocides-resistant strain and induced other

health impact such as allergy and dermatitis (NIOSH, 1998).

Previous studies in rats show that the levels of endotoxin-specific antibodies, including

IgG2a and IgE, were increased significantly (P < 0.05) in the rats exposed to

endotoxins. The results also shows that lung inflammatory responses may induce

without changing pulmonary function after repeated exposure to MWFs contaminated

with endotoxins. Thus, the study concluded that endotoxin-specific IgG2a and IgE may

be effective biomarkers for workers exposed to MWFs contaminated with endotoxins

in the workplace (Lim et al., 2005).

Based on Clinical Practice Guideline of The American Thoracic Society (ATS),

measurement of fractional nitric oxide (NO) concentration in exhaled breath (FENO) is

a quantitative, non-invasive, simple, and reliable method of measuring airway

inflammation that provides a complementary tool to other ways of assessing airways

disease (ATS, 2011). Studies shows that FENO level increased substantially after

exposure to MWFs in most subjects. Repeated measurements of FENO in workers

seem to be a relevant method to identify subjects with airway inflammation after

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exposure to MWFs. When more subjects have been included in the study, FENO may

also help to sort out what characteristics of the exposure can be associated with airway

inflammation (Andersson et al., 2012).

1.1 Problem Statement

Rapid shift of employment in manufacturing industry from the agriculture industry is

due to the globalization phenomena in Malaysia. Machining industry is one of the

industries in Malaysia that are rapidly growth (MIDA, 2012). Widespread use of

MWFs as lubricants was initiated along with automobile and aircraft manufacturing in

the beginning of the 1900s (Suuronen, 2009).

MWFs are critical issue because it causes a variety of health implications to the

machinists and are commonly used in machining industry as lubricant during metal

working process were used extensively as industrial lubricants to lubricate

metalworking operation by reducing friction at tool-work piece interfaces and carrying

away heat. The fluids are used to improve the machining performance thus prolong the

life of the cutting tool (HSE, 2011).

Soluble metalworking fluids (MWFs) are commonly used by machining industry.

These fluids represent a high potential for health risk due to high water content present

in the emulsion which is excellent for micro-organism growth (Duchaine et al., 2012).

Respiratory problem and skin problem may be implicated by the microbial

contaminants exposure of metalworking fluids (MWFs). Biological agents present in

the MWFs liquids are emitted in the formed of droplet bioaerosols during a rapid

rotation of the working metal tools which are inhaled by machine operator and causing

adverse health effects mainly on respiratory system (Cyprowski et al., 2007).

High number of cases of allergic alveolitis reported in the last 15 years (Bernstein

1995; Kreiss, 1997; Zacharisen 1998). Immune response to environmental antigens was

associated with this disease. Mycobacteria group was suspected as a causal agent in

infected workers. In the first study reporting cases of allergic alveolitis in metal turning

plants, IgGs against Pseudomonas fluorescens were investigated (Duchaine et al.,

2012).

According to Fornander et al. (2013), upper airway inflammation was a common

problem among machinists and it is reported that, about 39% of the workers exposed to

MWFs had airway symptoms. Some of the examples of airway symptoms are runny

nose, sore throat, nasal blockage and allergic rhinitis. The findings also imply effects

on the immune system among worker exposed to MWFs which may contribute to the

upper airway inflammation. MWFs exposure containing a mixture of reactive and pro-

inflammatory agents may induce a toxic response in the upper cell-linin, resulting in

decreased formation of normally expressed immune defence protein (Fornander, 2013).

Similar finding has been shown by Greaves et al. (1997), which they conclude that

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about two-fold higher risk for upper airway symptoms in workers exposed to MWFs

compared to unexposed workers.

A study conducted by Laitinen et al. (2007), showed that there is a significant elevation

of specific IgG antibodies response to bacteria antigen and serum IgG antibodies may

serve as indicator and tool in assessing the exposure to microbial contaminants. The

detection of many diseases is dependent upon accurate detection of particular

antibodies present in blood. However, the development of biochemical reagents that

can reliably detect these antibodies has proved remarkably challenging. The diagnosis

of many diseases relies heavily upon the accuracy of antibody detection. Assays to

detect antibodies using known antigens are used extensively to diagnose infectious and

autoimmune diseases. And antibodies exhibiting unique antigen binding patterns have

been shown to occur in diverse human diseases, including oncological, inflammatory,

and neurological and psychiatric disorders.

Based on study by John et. al. (2013), the utility of antibodies in diagnostics derives

from their intrinsic affinity and specificity, biochemical stability, and abundance in

blood. Nevertheless, the identification of rare antibody specificities indicative of

disease and the development of reagents for their accurate detection have proved

exceptionally difficult. Intersubjective variability of antibody specificities is a major

challenge to the development of accurate tests. Specifically, individual genetic and

stochastic variations that shape the antibody repertoire introduce heterogeneity in

disease antibody subpopulations (polyclonal variation, specificity, affinity, and titer)

that hinders uniform antibody detection.

Human exposure may occur via inhalation of airborne spores and hyphal fragments,

ingestion of contaminated food products, and skin or eye contact after handling of

contaminated material.The presence of antibodies to specific fungi could be used to

determine whether specific species of fungi found in a person’s environment are the

cause of health concerns a patient may be having. Although antibody reactivity is

necessary to identify certain fungi as possible sources of sensitization, the presence of

serum antibody against a specific fungus offers only supporting evidence of causation

in cases where environmental exposure has been confirmed (Douglas et. al., 2004).

A study by Immonen et. al. (2002), studied specific IgG to 24 fungi in students at

schools with identifiable fungal contamination and students at schools without

observable fungal contamination. The study found association between IgG to fungi

and exposure to fungi in the school. In addition, there was association between fungal

IgG levels and asthma, coughing, or wheezing (Immonen et. al., 2002). Another study,

compared IgG levels with a variety of fungi between 93 students in schools with

moisture problems and 33 students from a school without moisture problems. The

authors found relationship between IgG levels and “exposure” status or the presence of

asthma among study participants (Immonen et. al., 2002).

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1.2 Research Justification

Machining industry is one of the largest machining industries in Malaysia. MWFs are

widely used as lubricant in these machining industries. Most commonly used MWFS in

Malaysia industry is water-based which are very conducive for microbial growth such

as bacteria and fungus. Machining workers are most exposed to the contaminant of

metalworking fluids (Duchaine et al., 2012).

Exposures to MWFs were associated to various health diseases such as cancer,

respiratory outcome and skin disease (Park et al., 2009). Dermatitis is the most

common complaint associated with MWFs. Respiratory effects such as upper

respiratory irritation, asthma and hypersensitive pneumonitis (HP) are caused by

exposure to diluted MWFs, microbial contaminants and chemical contaminants of the

fluids (Park et al., 2009). However, there is limited study related to metalworking fluids

exposure yet in Malaysia. Therefore, more studies are required to study the interaction

effect between biological contaminants so that prevalence action can be applied to

prevent related health implications.

Nowadays, many workers spend at least 8 hours per day or more than 40 hours per

week in their workplace. Healthy workplace is an important concern as the

environmental exposures in the workplace will influence health, well-being and

productivity of the employees. However, there is lack of MWFs research and its

association with airway inflammation and also immune response conducted at this

country. Thus, MWFs research among machining workers which are exposed to MWFs

and its relation to microbial contaminant exposure need to be explored and therefore,

control measures to prevent health impact from the usage of metalworking fluids and

the intervention to overcome matter can be taken in the future.

1.3 Study Variables

In this study, the independent variable is the exposure of microbial contaminants in

metalworking fluids (MWFs) while the dependent variable is the serum IgG level and

airway inflammation level of workers.

1.4 Conceptual Framework

Figure 1.1 shows the conceptual framework of the study. In Malaysia, rapid shift of

employment in machining industry from the agriculture industry is due to the

globalization phenomena. Automotive, electronic and manufacturing are the examples

of machining industries in Malaysia that are rapidly growth (MIDA, 2012).

Metalworking fluids (MWFs) are widely used as lubricant in these machining

industries.

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Physical, chemical and biological hazard are main hazards from the usage of MWFs.

Most commonly used MWFs in Malaysia industry is water-based which are very

conducive for microbial growth such as bacteria and fungus. Thus, in this study we

were focused on the biological hazard which comprises bacteria and fungus. All types

of hazards could affect human health through inhalation, ingestion and skin contact.

These microorganisms exposure will cause the physiological response such as airway

inflammation and respiratory problem to the human. Besides that, this microbial

exposure also will trigger immune response. Thus, antibodies in the human blood are

one of the biomarkers and indicator for the specific microbial exposure. In this study,

specific IgG antibodies in the blood were studied to study the microbial exposure.

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Metal Machining

Biological

(Bacteria, Fungi)

Chemical

Painting Metalworking

Fluids

Physical

Physiological

Response

Airway Inflammation

Inhalation Skin Contact

Industry

IgM

IgE

IgG Blood

Respiratory Symptom

Skin Symptoms

Electronics Automotive Manufacturing

Ingestion

Confounding Factors

• Age

• Employments

years

• Medical and

occupational

history

Figure 1.1: Conceptual Framework

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1.6 Research Objective

1.6.1 General Objective

To study the relationships between serum IgG levels and airway inflammation (FeNO

level) with the microbial exposure among MWFs workers.

1.6.2 Specific Objectives

1. To determine the social demography, residential information, employment and

workplace characteristics of the respondents in metal working process.

2. To determine the species and levels of bacteria and fungi in MWFs in various

work sections.

3. To determine the distribution of total and specific serum IgG levels, FeNO levels,

respiratory and skin symptoms of the respondents in various work section.

4. To determine the correlation between serum IgG and FeNO levels with the

microbial levels in MWFs.

5. To determine the relationship between microbial levels with workplace

characteristics.

6. To determine the relationship between serum IgG and FeNo levels with

individual, residential, workplace characteristics of the respondents and microbial

levels.

7. To determine the relationship between reported health symptoms serum IgG and

FeNO levels.

1.7 Research Hypothesis

1. There are significant correlation between serum IgG and FeNO level with the

microbial levels of MWFs among respondents in metal working process.

2. There are significant relationships between microbial levels with individual and

workplace characteristics of the respondents.

3. There are significant relationships between serum IgG and FeNO levels with

individual, residential, workplace characteristics of the respondents and microbial

levels.

4. There are significant relationships between reported health symptoms with serum

IgG and FeNO levels of the respondents.

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