Title Page
ABSTRACT
국문 초록
Contents
CHAPTER 1. BACKGROUND 21
1.1. Biocidal active substances and their toxicity 21
1.2. Biocidal products regulation 24
1.3. Occupational exposure to biocides and health risks 30
1.4. Environmental exposure to biocides and health risks 32
1.5. Study design and aims 38
CHAPTER 2. HEALTH RISKS OF PEST CONTROL AND DISINFECTION WORKERS AFTER THE COVID-19 OUTBREAK IN SOUTH KOREA 40
2.1. Introduction 40
2.2. Materials and methods 42
2.2.1. Study participants 42
2.2.2. Questionnaire survey 43
2.2.3. Selection of target chemicals for the risk assessment 43
2.2.4. Toxicity endpoints 44
2.2.5. Exposure assessment 45
2.2.6. Risk characterization 49
2.2.7. Statistical analysis 49
2.3. Results 50
2.3.1. Characteristics of pest control and disinfection workers 50
2.3.2. Biocidal active ingredients used in pest control and disinfection 53
2.3.3. Target chemicals for the risk assessment 55
2.3.4. Toxicological endpoints of target chemicals for the risk assessment 57
2.3.5. Exposure factor and estimated exposure dose 58
2.3.6. Risk characterization 63
2.3.7. Health symptoms 66
2.4. Discussion 67
CHAPTER 3. EXPOSURE TO BIOCIDE AND THEIR POTENTIAL EXPOSURE SOURCES AMONG KOREAN CHILDREN, ADOLESCENTS, AND ADULTS: KOREAN NATIONAL ENVIRONMENTAL HEALTH SURVEY 2018-2020 71
3.1. Introduction 71
3.2. Materials and methods 73
3.2.1. Study participants 73
3.2.2. Urinary biocide exposure assessment 73
3.2.3. Statistical analysis 74
3.3. Results 76
3.3.1. Characteristics of study participants 76
3.3.2. Comparison urinary TCS, parabens, and 3-PBA levels with other national biomonitoring studies 81
3.3.3. Exposure factors for TCS, parabens, and 3-PBA 83
3.4. Discussion 116
3.4.1. Urinary concentration of TCS, parabens, and 3-PBA in Korean general population 116
3.4.2. Exposure to TCS, parabens, and 3-PBA through personal care products 117
3.4.3. Exposure to TCS, parabens, and 3-PBA through pesticide products 118
3.4.4. Exposure to TCS, parabens, and 3-PBA through food 118
CHAPTER 4. URINARY LEVELS OF TRICLOSAN, PARABENS, AND 3-PHENOXYBENZOIC ACID AND ALLERGIC DISEASES AMONG CHILDREN, ADOLESCENTS, AND ADULTS: A POPULATION-BASED STUDY IN KOREA 120
4.1. Introduction 120
4.2. Materials and methods 123
4.2.1. Study participants 123
4.2.2. Measurement of urinary triclosan (TCS), parabens, and 3-phenoxybenzoic acid (3-PBA) 125
4.2.3. Ascertainment of allergic symptoms 125
4.2.4. Covariates 126
4.2.5. Statistical analysis 126
4.3. Results 128
4.3.1. Characteristics of study participants 128
4.3.2. Distribution of urinary TCS, parabens, and 3-PBA concentrations 131
4.3.3. Effects of urinary TCS, parabens, and 3-PBA levels on the allergic disorders 136
4.3.4. Joint effects of urinary TCS, parabens, and 3-PBA levels on the allergic disorders 140
4.4. Discussion 150
CHAPTER 5. CONCLUSION 155
REFERENCES 157
APPENDICES 174
A. Eight sub-indexes and scores for defining product ingredient safety index. 174
B. Equations for calculating toxicity reference values by the exposure route. 177
C. Summary of toxicological endpoints for ingredients in biocidal product. 178
D. Korean biocide exposure factors. (NIER, 2017). 180
E. Product ingredient safety index (PISI) scores of chemicals. 181
F. Univariate effects of TCS, parabens, and 3-PBA mixture on atopic dermatitis in (A) preschool children, (B) school children, (C) adolescents, and (D) adults. 183
G. Bivariate effects of TCS, parabens, and 3-PBA mixture on atopic dermatitis in (A) preschool children, (B) school children, (C) adolescents, and (D) adults. 185
H. Univariate effects of TCS, parabens, and 3-PBA mixture on allergic rhinitis in (A) preschool children, (B) school children, (C) adolescents, and (D) adults. 187
I. Bivariate effects of TCS, parabens, and 3-PBA mixture on allergic rhinitis in (A) preschool children, (B) school children, (C) adolescents, and (D) adults. 189
Table 1-1. Molecular structure and physiochemical properties of major biocides found in general population. 22
Table 1-2. The product type regulated among United States (US) and European Union (EU). 25
Table 1-3. The product type regulated before and after implementing the Consumer Chemical Products and Biocides Safety Act (K-BPR). 27
Table 1-4. The most used ingredient by product type among existing active substance designated under the K-BPR. 28
Table 1-5. Previous studies evaluated health risks among biocide applicators. 31
Table 1-6. Exposure characteristics among different age groups of general population. 33
Table 1-7. Previous studies evaluated the exposure sources of biocide and allergic disorders among general populations. 34
Table 1-8. Previous studies evaluated the associations between biocide and allergic disorders among general populations. 37
Table 2-1. Working method, product type, and exposure scenario of pest control and disinfection workers. 46
Table 2-2. The pre- and post-COVID-19 pandemic demographic and work-related traits of pest control and disinfection workers. 51
Table 2-3. Active ingredients of biocides employed in pest control and disinfection practices pre- and post-COVID-19 pandemic. 54
Table 2-4. Product ingredient safety index (PISI) scores on inhalation (0-3 points), dermal (0-3 points), carcinogenicity (0-4 points), and target chemicals for the risk assessment. 56
Table 2-5. A summary of toxicological endpoints calculated for the target chemicals. 57
Table 2-6. Estimated exposure concentration (μg/m³) and LAEC (μg/m³) for inhalation risk assessment. 61
Table 2-7. Estimated exposure concentration (μg/kg/day) during averaging work time and lifetime average daily dose (µg/kg/day) for dermal risk assessment. 62
Table 3-1. Geometric means and standard errors (μg/g-creatinine) for urinary TCS, parabens, and 3-PBA by preschool children participants' characteristics. 77
Table 3-2. Geometric means and standard errors (μg/g-creatinine) for urinary TCS, parabens, and 3-PBA by school children participants' characteristics. 78
Table 3-3. Geometric means and standard errors (μg/g-creatinine) for urinary TCS, parabens, and 3-PBA by adolescent participants' characteristics. 79
Table 3-4. Geometric means and standard errors (μg/g-creatinine) for urinary TCS, parabens, and 3-PBA by adult participants' characteristics. 80
Table 3-5. Urinary TCS, parabens, and 3-PBA levels (μg/g-creatinine) among Korean compared to that of other national biomonitoring program. 82
Table 3-6. Multiple linear regression coefficient (β) and standard errors for TCS, parabens, and 3-PBA in personal care products among preschool children (n=556). 84
Table 3-7. Multiple linear regression coefficient (β) and standard errors for TCS, parabens, and 3-PBA in pesticides products among preschool children (n=556). 86
Table 3-8. Multiple linear regression coefficient (β) and standard errors for TCS, parabens, and 3-PBA in dietary factors among preschool children (n=556). 88
Table 3-9. Multiple linear regression coefficient (β) and standard errors for TCS, parabens, and 3-PBA in personal care products among school children (n=701). 92
Table 3-10. Multiple linear regression coefficient (β) and standard errors for TCS, parabens, and 3-PBA in pesticides products among school children (n=701). 94
Table 3-11. Multiple linear regression coefficient (β) and standard errors for TCS, parabens, and 3-PBA in dietary factors among school children (n=701). 96
Table 3-12. Multiple linear regression coefficient (β) and standard errors for TCS, parabens, and 3-PBA in personal care products among adolescents (n=731). 100
Table 3-13. Multiple linear regression coefficient (β) and standard errors for TCS, parabens, and 3-PBA in pesticides products among adolescents (n=731). 102
Table 3-14. Multiple linear regression coefficient (β) and standard errors for TCS, parabens, and 3-PBA in dietary factors among adolescents (n=731). 104
Table 3-15. Multiple linear regression coefficient (β) and standard errors for TCS, parabens, and 3-PBA in personal care products among adults (n=4,195). 108
Table 3-16. Multiple linear regression coefficient (β) and standard errors for TCS, parabens, and 3-PBA in pesticides products among adults (n=4,195). 110
Table 3-17. Multiple linear regression coefficient (β) and standard errors for TCS, parabens, and 3-PBA in dietary factors among adults (n=4,195). 112
Table 4-1. Demographic characteristics of the study participants. 129
Table 4-2. Multiple logistic regression odds ratios (95% confidence intervals) for atopic dermatitis with changes of urinary TCS, parabens, and 3-PBA levels.... 137
Table 4-3. Multiple logistic regression odds ratios (95% confidence intervals) for allergic rhinitis with changes of urinary TCS, parabens, and 3-PBA levels. 139
Table 4-4. Posterior inclusion probabilities (PIPs) for group inclusion and conditional inclusion into atopic dermatitis, using the BKMR model. 143
Table 4-5. Posterior inclusion probabilities (PIPs) for group inclusion and conditional inclusion into allergic rhinitis, using the BKMR model. 148
Fig. 1-1. The number of active substances with each health hazard (bottom) by biocidal product types (left). Numbers at the top of the figure indicate the number of chemicals... 29
Fig. 1-2. Schematic figure of biocide mixture scenario in Korea. 36
Fig. 1-3. Study design to investigate the associations between occupational exposure and environmental exposure to biocide and associated health risks in South Korea. 38
Fig. 2-1. The exposure factors by product type before and after the COVID-19 outbreak include work frequency (work/year), amount (g/use), and work duration (hour/work), as shown in the data. A black star (*) denotes a significant difference before... 59
Fig. 2-2. The margin of exposure (MOE) for selected chemicals through two different inhalation exposure routes before and after the COVID-19 outbreak is presented. 63
Fig. 2-3. The margin of exposure (MOE) for selected chemicals through three different dermal exposure routes before and after the COVID-19 outbreak. a The results of fipronil... 64
Fig. 2-4. The cancer risks associated with dichlorvos exposure via inhalation and dermal routes before and after the COVID-19 outbreak. 65
Fig. 2-5. The percentage of health symptoms reported by pest control and disinfection workers is presented, categorized based on their working years (〈10 years or ≥10 years). A... 66
Fig. 3-1. Decision tree to identify exposure sources to (A) TCS (B) MP (C) EP (D) PP (E) BP and (F) 3-PBA among preschool children. GM, geometric mean; TCS, triclosan; MP, methyl paraben; EP, ethyl paraben; PP, propyl paraben; BP,... 90
Fig. 3-2. Decision tree to identify exposure sources to (A) TCS (B) MP (C) EP (D) PP (E) BP and (F) 3-PBA among school children. GM, geometric mean; TCS, triclosan; MP, methyl paraben; EP, ethyl paraben; PP, propyl paraben; BP, butyl... 98
Fig. 3-3. Decision tree to identify exposure sources to (A) TCS (B) MP (C) EP (D) PP (E) BP and (F) 3-PBA among adolescents. GM, geometric mean; TCS, triclosan; MP, methyl paraben; EP, ethyl paraben; PP, propyl paraben; BP, butyl... 106
Fig. 3-4. Decision tree to identify exposure sources to (A) TCS (B) MP (C) EP (D) PP (E) BP and (F) 3-PBA among adults. GM, geometric mean; TCS, triclosan; MP, methyl paraben; EP, ethyl paraben; PP, propyl paraben; BP, butyl paraben; 3-PBA,... 114
Fig. 4-1. Flow chart of study participants in the 2018-2020 Korean National Environmental Health Survey. TCS, triclosan; 3- PBA, 3-phenoxybenzoic acid. 124
Fig. 4-2. Pearson correlations among urinary concentrations of TCS, parabens, and 3-PBA in (A) preschool children, (B) school children, (C) adolescents, and (D) adults. X indicates... 130
Fig. 4-3. Geometric means and 95% confidence intervals (μg/L) for urinary concentrations of TCS, parabens and 3-PBA by preschool children participant's characteristics. The red star (*) indicates a significant difference between the groups... 132
Fig. 4-4. Geometric means and 95% confidence intervals (μg/L) for urinary concentrations of TCS, parabens and 3-PBA by school children participant's characteristics. The red star (*) indicates a significant difference between the groups (p〈0.05).... 133
Fig. 4-5. Geometric means and 95% confidence intervals (μg/L) for urinary concentrations of TCS, parabens and 3-PBA by adolescent participant's characteristics. The red star (*) indicates a significant difference between the groups (p〈0.05). TCS,... 134
Fig. 4-6. Geometric means and 95% confidence intervals (μg/L) for urinary concentrations of TCS, parabens and 3-PBA by adult participant's characteristics. The red star (*) indicates a significant difference between the groups (p〈0.05). TCS,... 135
Fig. 4-7. The overall effects of TCS, parabens and 3-PBA mixture on the atopic dermatitis estimated by the Bayesian Kernel Machine Regression (BKMR) in (A) preschool children,... 141
Fig. 4-8. The overall effects of TCS, parabens and 3-PBA mixture on the allergic rhinitis estimated by the Bayesian Kernel Machine Regression (BKMR) in (A) preschool children,... 146