Children’s Environmental Health in Thailand: Past, Present, and Future

Background: There is increasing evidence of a link between environmental pollution and preventable diseases in developing countries, including Thailand. Economic development has generated several types of pollution that can affect population health. While these environmental health effects can be observed throughout life, pregnant women and children represent particularly vulnerable and sensitive groups. Methods: The published epidemiological literature investigating environmental chemical exposure in Thai children was reviewed, highlighting those that investigated associations between exposure and subsequent health outcomes. Results: The majority of the Thai epidemiological studies on environmental health in children were cross-sectional in design, with some demonstrating associations between exposure and outcome. The three main types of chemical exposure in Thai children were pesticides, heavy metals, and air pollution, which resulted from agricultural activities in countryside areas, industrial zones (both registered and unregistered establishments), mining, and traffic in inner cities. Major health outcomes included detrimental effects on cognitive function and cancer risk. Pesticide exposure was focused on, but not limited to, agricultural areas. The success of the Thai environmental policy to introduce lead–free petrol can be demonstrated by the decline of mean blood lead levels in children, particularly in urban areas. However, unregistered lead-related factories and smelters act as hidden sources. In addition, there is increasing concern, but little acknowledgement, about the effects of chronic arsenic exposure related to mining. Lastly, air pollution remains a problem in both dense city populations due to traffic and in rural areas due to contamination of indoor air and house dust with heavy metals, endotoxins and other allergens. Conclusions: The increasing number of published articles demonstrates an improved awareness of children’s environmental health in Thailand. Chemical hazards, including the improper use of pesticides, environmental contamination with heavy metals (lead and arsenic), and air pollution in inner cities and indoor air, continue to be growing issues.

as traffic-related emissions; asbestos construction materials; untreated manufacturing waste; electronic appliance waste; heavy metal contaminants such as lead, arsenic, cadmium from anthropogenic activities such as mining; pesticides; and persistent organic pollutants (POPs). Since 2011, The World Bank has categorized Thailand as an upper-middle income economy based on gross national income (GNI) per capita, with the country's major income source changing from agriculture to the industrial sector [3]. However, economic development via industrialization and globalization is increasing at a greater rate than environmental preservation. This has generated several types of pollution that can affect population health. Health effects can occur throughout life; however, pregnant women and children represent particularly vulnerable and sensitive groups [2].
The main ministry for pollution control is the Ministry of Natural Resources and Environment, especially the Department of Pollution Control. From a public and environmental health policy perspective, the challenges to children's environmental health in Thailand include the lack of efficiently regulated controls and the reluctance to recognize and/or use the precautionary principle. The environmental legislation in Thailand is based on proof of evidence. In addition, awareness of environmental health problems is relatively limited among health care providers as well as the general population. Compared to 20 years ago, however, the approach of the health care system towards environmental problems has improved. The positive direction of public policy and research in children's environmental health in Thailand includes several international collaborations that reflect increasing awareness and the opportunity to exchange knowledge on environmental health. Both government agencies and non-governmental organizations such as Ecological Alert and Recovery-Thailand (EARTH) are involved in coordinating such initiatives. As a result, research is increasing, particularly as advances in technologies for the detection, monitoring, and intervention of exposures are made. Furthermore, collaboration could augment harmonization of methods and results that are very useful to evaluate uncommon outcomes such as cancer. Multidisciplinary government inter-departmental and agency collaboration is essential to help protect Thai children from unhealthy environments.

Hazard Identification: Physical, Biological, and Chemical
The catastrophic tsunami in 2004, which killed 230,000-280,000 people in 14 countries, including Thailand, was one of the most tragic environmental emergency disasters. Flooding and drought are also increasing, with possible links to climate change and global warming. Radiation exposures (environmental and medical) receive less attention in the literature from Thailand. However, there is concern over radon exposure in specific geographical locations [4,5]. and also about radiation used for medical diagnostics and interventions for some pediatric patients [6,7]. Thus, in combination with the multiple pollutants already mentioned as a result of urbanization, globalization and industrialization, there is a wide variety of environmental exposures relevant to children's environmental health in Thailand. For the purposes of this review, we limited exposure to environmental chemicals and air pollution, exposures most relevant to children in Thailand.

Objectives
This review aims to 1) conceptualise children's environmental health in Thailand through a comprehensive review of the available epidemiological literature investigating environmental chemical exposure in Thai children, and 2) propose the future direction of research, policy, and practice to improve the health of children in Thailand and similar upper-middle income countries.

Methods
We searched the health research databases on children's environmental health in Thailand in the Medline/Pub-Med, Web of Science, EMBASE, and Scopus databases using the PICO (Problem/Patient/Population, Intervention/Indicator, Comparison, Outcome, and (optional) Time element or Type of Study) search strategy shown in Table 1. Randomized controlled, retrospective, prospective, case-controlled, and cross-sectional studies, and case reports on human cohorts in Thailand from 1980-2017 were included. Literature published in Thai and/or English was included to minimize selection bias from language barriers. Articles were excluded if they: 1) did not meet the inclusion criteria, 2) focused on physical hazards including radiation, electromagnetic field, noise, heat, cold, or injury 3) focused on psycho-social hazards including stress, poverty, or inequity, and 4) focused on biological hazards (except aeroallergens; mold, fungi, and cockroaches) such as bacteria, viruses, insects, plants, birds, or animals. Aeroallergens were included due to the link with chronic respiratory symptoms.
All article titles and abstracts (where appropriate) were screened by two independent reviewers (RS and CW). A third independent reviewer (EM) provided a final decision on the inclusion/exclusion of articles where the first two reviewers had disagreed. Thus, the final list of studies for review was selected in agreement by at least 2 out of 3 independent reviewers (RS, CW, EM). The full text of Thai articles was retrieved from Journal of Medical Association of Thailand and Thai Pediatric Journal. All available full-text articles were critically reviewed to identify the major environmental chemical and air pollution threats to children living in Thailand, highlighting those that investigated associations between exposure and subsequent health outcomes. Relevant studies cited in the selected studies were also included as appropriate. Figure 1, 343 articles were identified from four databases, resulting in 273 unduplicated articles. Following screening of titles and abstracts, 79 articles were selected for critical review. Of these 79 articles, 26 were further excluded due to restricted access to the full paper. An additional two articles, which were cited in the key article of arsenic exposure, were included later. Therefore, a total of 55 full-text articles were critically reviewed and summarized in Tables 2, 3, and 4. The majority of exposures were pesticides (organochlorine, organophosphate, paraquat, glyphosate, or paraquat), heavy metals (lead, arsenic, cadmium, or mercury), or air pollution (ambient air pollution or environmental tobacco smoke). The sources of these exposures varied by geographical region.
Factors associated with pesticide exposure included living close to agricultural farmland, frequency of agricultural field visit, agricultural activities, insecticide use in the home, household environment, and child-specific factors (such as frequency of pesticides used on farm, being a member of a rice farming family, proximity to rice farm, being with parent on rice farm, playing on rice farm, parentally observed dirt on body) [19]. In addition, Liu et al. demonstrated the indirect transfer of pesticide from the farmer to child through contamination of the home environment [14]. The health outcomes associated with organochlorine (dichlorodiphenyltrichloroethane; DDT) or  [8] or neurotoxicity [12], respectively. The third study that investigated health outcomes showed no association between organophosphate or pyrethroid exposure and neurobehavior in school children [11].

Heavy Metal
There were 21 full-text articles available that investigated heavy metal exposure in Thai children ( Table 3), nine of which measured both exposure and subsequent health effects in the same cohorts (lead, three articles; arsenic, four articles; cadmium, one article; and mercury, one article). The current sources of lead exposure in Thai children (following the ban on leaded fuel) appear to be para-occupational and related to household location and activities [21][22][23][24][25][26][27][28][29][30]. The high risk areas of lead exposure were boatyard and shipyard factories or locations of former mining and smelting. Maharachpong et al. demonstrated lead contamination in coastal communities connected with boat repair and boat building activities [31]. Increased levels of lead in household dust were observed in households with a member that worked on boat repair (either in boatyards or at home). Similarly, Pusapukdepob et al. demonstrated lead contamination from mining, where the waste from lead mining that was discharged directly into a stream near Klity village in 1998 was still present in the sediment over a decade later [29]. The risk factors for elevated blood lead levels were anemia, large families, male gender, age under two years, access to lead-acid batteries, and residence in a house with peeling paint [21,22,30,32,33]. The health outcomes associated with chronic lead exposure in Thai children were cognitive deterioration and dental caries [26,29].
The studies on arsenic exposure in Thai children were all focused in the Ron Pibul district, Nakorn Srithammarat province, Southern region of Thailand. Here, former tin mining and smelting activities had led to the contamination of drinking water, soil and some of the food chain with arsenic [34][35][36]. Furthermore, the level of arsenic exposure was exacerbated by the children's risk behavior, such as playing with soil and no hand-washing before eating [34]. The health outcome associated with arsenic exposure in utero and through childhood was increased cancer risk, where hypomethylation of inflammatory genes (COX2, EGR1, and SOC3) positively correlated with levels of 8-nitroguanine, increased DNA damage and reduce DNA repair capacity [35,36].
Likewise, cadmium exposure in the Northern region appeared to be mainly a result of tin mining activity leading to contamination of land, water, and eventually the staple food (rice grown in contaminated soil) [37]. However, the level of cadmium exposure in Thai children appeared to be decreasing due to cessation of mining activity and subsequent declining environmental contamination [38]. It is therefore hoped that the renal effects associated with cadmium exposure the in local Thai children will also continue to decrease [37,39]. Indeed, Swaddiwudhipong et al. have reported no association between cadmium exposure and blood pressure in children [37].
Finally, children attending an elementary school near a small-scale gold mine in Phichit demonstrated elevated urinary inorganic mercury levels. However, the hazard quotient (HQ) based on the inorganic mercury exposure was <1 in these school children [40], suggesting they are not at risk of nephrotoxicity from inorganic mercury at this level of exposure [41].    • PM10 levels exceeded 120 mg/m 3 for 14 days.
• When PM10 levels were >120 mg/ m 3 , the daily reported nasal irritation of asthmatic children was significantly higher than when PM10 levels were ≤ 120 mg/m 3 • PEFR did not change with different ambient PM10 levels in both groups.
• Elevated levels of PM10 concentrations in Bangkok affected respiratory symptoms of schoolchildren with and without asthma.

SO2
Aekplakorn et al. The lifetime cancer and non-cancer risk in all high-risk group including children were in acceptable range based on the US EPA health risk assessment.

Air Pollution
The majority of the 17 full-text articles available investigated exposure to outdoor air pollution, and secondhand or environmental tobacco smoke (ETS) ( Table 4). The source of outdoor air pollution depended on the geographical area, and included traffic-related pollution in inner cities, petrochemical factories in coastal provinces, coal power plants and agricultural burning activities in the northern region of Thailand. Traffic-related and automotive emissions, including diesel exhaust particles, have been reported in urban areas and linked to both cancer and non-cancer risks [47][48][49][50][51][52]. Studies of petrochemical industrial estates have focused on volatile organic compounds (VOCs), particularly benzene and polyaromatic hydrocarbons (PAHs), demonstrating associations with both occupational and environmental health in central Thailand [48,[52][53][54][55]. For example, exposure to 1,3-butadiene and PAHs in children living close to petrochemical industries was associated with increased cancer risk [52].
Outdoor biomass burning activities (including forest fires, agricultural, and refuse burning) appear to be a major sources of air pollution in Northern Thailand, potentially creating PM2.5-bound PAHs [56]. However, there was limited evidence of related health outcomes (either respiratory or non-respiratory diseases such as cancer risk) [56].
There have been two large studies assessing the exposure of Thai children to secondhand smoke inhalation: 1) the Prospective Cohort Study of Thai Children (PCTC) covering Bangkok and across Thailand (3,256 participants, all were parents of infants aged less than 1 year) [57] and 2) the fifth-round census of the Kanchanaburi Demographic Surveillance System (KDSS) covering the Kanchanaburi province (28,248 participants, 2,596 children of 15-19 years) [58]. Anuntaseree et al. reported that the prevalence of at least one smoker in a household was 47.2%, paternal smoking in the presence of an infant was 35.1%, and maternal smoking was 0.3% [57]. Paternal smoking was significantly associated with an age of 25-34 years, education lower than secondary school, and a Muslim father [57]. Thongthai et al. reported the prevalence of secondhand smoke exposure in 60% of the Kanchanaburi population (24.6% and 1% prevalence in male and female teenagers, respectively) [58]. The smokers in this report were more likely to be older and male, while those exposed to secondhand smoke tended to be younger and female. Despite these surveys, there was only one study that investigated both ETS exposure and health outcomes in Thai children, which demonstrated an association between ETS exposure and an increase of the severity of respiratory syncytial virus (RSV) infection in young children [59].
There was one study that examined sensitization in Thai children suffering from allergic rhinitis, reporting that the predominant aeroallergen to which patients were sensitized in Bangkok was house dust mite [60]. A subsequent exposure study collected dust from the mattresses of young children in Thailand and Singapore [61]. Dust mite allergen in rural Thailand was less than in urban Singapore and positively correlated with air-conditioning use, while the endotoxin level in rural Thailand was higher (particularly in agricultural areas) compared to Singapore. The cleaning practices and type of mattress were associated with endotoxin levels.

Specific Geographical Area of Health Effect Related to Environmental Exposure in Thailand
Focusing on the evidence of health effects related to environmental exposure in particular geographical areas in Thailand (Table 5), six major health effects were identified: neurotoxicity (IQ and neurodevelopment), respiratory impairment, renal effect, endocrine disorder, allergic diseases, and cancer risk (probably via DNA damage and impaired DNA repairing). The IQ deterioration from chronic lead exposure was reported in Klity village, Kanchanaburi (central region) [29]. The neurodevelopmental effect was associated with in utero exposure to organophosphate in Amnatchareon, Nakhon Sawan and Kanchaburi [12]. In contrast, in the greater Bangkok area, which was rice farming area, organophosphates, chlorpyrifos, and pyrethroid were detected but there was no statistically significant association with neurobehavioral problems in school age children [11]. Respiratory effects, such as declined pulmonary function or chronic respiratory symptoms, were associated with air pollution (PM) in the Maemoh district, Lampang, and Bangkok [62,64]. Early renal effects from chronic cadmium exposure, reduced cord serum T4 from organochlorine exposure, and allergy risk of allergic rhinitis and atopic dermatitis from air pollution (DEPs) were found in Tak and Chiang Mai, respectively [37,39,67]. Increased cancer risk and DNA damage, and decreased DNA repair capacity, were detected in Bangkok and the Ron Phibul district, Nakorn Sri Thammarat. However, the culprit hazards were different: air pollution (benzene, traffic-related PAH) in Bangkok, and arsenic in the Ron Phibul district [34, 35, 47-52, 59, 60, 63, 65, 68].

Children's Environmental Health in Thailand: Past Issues
Before the 21st century, Thailand was classified as a lowermiddle income country. Industrialization had begun, but with less awareness of the environmental impact. This led to the major pollution of air, water and soil, which in turn had a negative effect on the population's health. A key legislative change that positively impacted environmental health in Thailand (including children's health) was the lead-free gasoline policy in 1993. This policy gradually reduced lead in fuel from 1984 onwards. Unleaded petrol was introduced in 1991, and fuel containing lead was completely phased out in 1993. The resulting impact was demonstrated by the improvement of average air quality in Bangkok in 1998. Studies showed that over a one-month period the lead level in ambient air was below the standard limit of 1.5 μg/m 3 . In addition, the blood levels of lead in children living in urban areas also showed a decline. By 2002, blood lead levels in Bangkok children had decreased compared to those levels in neonates and school children measured in 1989 [32,69].

Pesticides
Traditional pest management (with chemical pesticides) in Thailand seems to be a more common practice than integrated pest management [13]. Pesticides, including insecticides, herbicides, fungicides, rodenticides, fumigants, and repellants, are widely used for both agricultural and domestic management. Each product can be subdivided according to chemical structure, which reflects mechanisms of action and toxicity. Organophosphate, carbamate, and pyrethroid insecticide use is currently allowed in Thailand. In contrast, the use of the organochlorine dichlorodiphenyltrichloroethane (DDT) was banned in 1989. Between 1949 to 1989, DDT was used as a pest control in farming and to control the spread of malaria by limiting the number of mosquitoes. However, exposure to DDT was detected via biomonitoring in agricultural areas a number of years later [8,9]. This result may be a result of the bioaccumulative and persistent nature of DDT, or it may reflect illegal use. DDT acts as an endocrine disruptor and showed a negative association with thyroid hormones in the cord blood of newborn Thai children [8]. Chronic exposure in children can occur via air, soil, dust, food, and through direct exposure to residential/garden agricultural products or product residues. Of highest risk are children and pregnant women who live in agricultural areas or live with agriculturists [74]. Contact with potentially contaminated dirt/soil, handto-mouth activity, and walking/playing on the farm all represent possible means of exposure in children. These children also encounter more accidental exposures as a result of products being taken home and spilled [10, 12-14, 19, 20]. However, only two studies have evaluated subsequent health effects in Thai children, both of which focused on neurodevelopment. The first, a case-controlled study in school children, showed no association between organophosphate (dialkylphosphates; DAPs) or pyrethroid exposure and neurobehavior [11]. In contrast, the second, which looked at a birth cohort in an unspecified agricultural area (50% of participants were farm workers), demonstrated a negative association between organophosphate exposure (diethyl phosphate) and cognitive and motor development of infants at five months of age [12]. This discordance may be due to the difference in age group, neurobehavioral assessment, and the timing/level of pesticide exposure. Furthermore, there is increasing evidence from other studies outside Thailand supporting the neurotoxicity of low-dose chronic organophosphate exposure [75,76].

Heavy metals
Although the lead-fuel ban has had a major impact on lead exposure in Thai children, other sources of environmental lead contamination remain. These include former mining areas, shipyards, lead-based paints, and the use of car batteries in the household. Indeed, the extensive use of pumbopumpic oxide (Pb 3 O 4 ) in boat repairing activities in the southern region of Thailand has caused lead contamination of the surrounding air, soil and dust [31]. As a result, lead exposure in children living in such contaminated environments is unavoidable. Chronic arsenic exposure in Thai children has been detected in the vicinity of the former tin mining and smelting activities in the Ron Pibul district of the Nakorn Srithammarat province in the Southern region of Thailand. There were more than 1,000 reported cases of arsenicosis in 1987 and mining was eventually banned in 1994, resulting in arsenopyrite and pyrite-rich waste piles [34,35]. Arsenic exposure from this waste remains, as demonstrated by the detection of biomarkers of exposure and disease reported in multiple studies [34][35][36]. The major health risks associated with arsenic exposure are carcinogenic [77]. Indeed, early life arsenic exposure has been associated with DNA damage (8-nitroguanine or 8-OHdG formation) and activation of inflammatory genes (COX2, EGR1 and SOC3) through a proposed epigenetic mechanism involving hypomethylation and increased mRNA expression [35,36,45].
Chronic cadmium exposure in Thai children has not been widely studied and the current source of exposure appears to be limited to the former zinc mining areas of the Mae Sot district, Tak province, northern Thailand. This zinc mine was established in 1977 and environmental cadmium contamination was first demonstrated in 1998 [78]. Most of the adverse health effects were identified in adults. However, there were two studies reporting cadmium exposure in children and potential adverse effects on renal impairment [37,39]. Although cadmium environmental contamination appeared to decline after cessation of the zinc mining operation, other sources of environmental cadmium exposure, such as second-or third-hand smoking exist and should be considered.

Air pollution
Like other developing countries, air pollution in Thailand is prominent in inner cities and industrialized provinces, with the specific types of air pollution depending upon the geographical area [2]. The main sources of outdoor air pollution in Thailand are: traffic in cities and industrial provinces (VOCs, benzene, PAHs, and particulate matter); petrochemical industries in coastal areas (VOCs, benzene) areas; and coal power plant and open biomass burning in the northern region of Thailand (particulate matter and PAH). In contrast, ETS, which can be both an indoor and outdoor air pollutant, is more generally prevalent across Thailand. Approximately 50% of the Thai population has contact with secondhand smoke, which is similar to the global secondhand tobacco smoke prevalence [79]. Likewise, house-dust and/or cockroach allergens represent another more widespread indoor air exposure across Thailand [80]. Sensitization to these allergens is very common in Asian countries, including Thailand [60,61]. Some sources of indoor air pollution are also linked with outdoor air pollution and children tend to spend more time in indoors than outdoors. For example, children can be exposed via direct transfer of chemicals from parents working in agriculture [14]; dust in households living close to boat repair yards contain higher levels of lead [31]; and endotoxin levels are higher in households located in agricultural areas [61]. The latter observation may be linked to the hygiene hypothesis and might explain the lower prevalence of allergic disease in Thailand compare to other Western countries [81]. The health outcomes associated with air pollution in Thai children were well-established effects on the respiratory system, and some genotoxic and potentially carcinogenic outcomes [47,49,51,[63][64][65]67].
It is also important to note that those studies that demonstrated no association between environmental exposures and health outcomes in Thai children are also very useful from both a scientific and policy perspective. They highlight those outcomes that are less likely to be linked with environmental exposures, identify more resistant life stages, may help set thresholds of exposure/toxicity and focus the limited resources on the most important issues.

Children's Environmental Health in Thailand: Proposed Future Direction of Research
To further improve children's environmental health in Thailand, we suggest that: 1) future epidemiological and molecular studies combine exposure and health outcome assessment in a prospective design and incorporate stateof-the-art technologies where appropriate, 2) regular monitoring of the levels of current hazards such as pesticides, heavy metals and air pollutants should be considered, and 3) vulnerable populations such as pregnant women and children be given greater attention. Such studies would help to identify the key pollutants associated with children's health in Thailand, and develop policy changes that will achieve the greatest impact.

Conclusions
Environmental health in Thailand is improving in terms of awareness, expanding knowledge, and increasing environmental conservation. However, pesticide, heavy metal, and air pollution exposures are still major issues that can affect the health of the next generation. Further advancement of children's environmental health in Thailand now requires a greater understanding of the links between exposures and outcomes, education of the public and policymakers, development of policies in environmental health, improved regulations, and enhanced coordination between organizations.