Microplastics in the Asia-Pacific Region in the Plasticene Era: Exposures and Health Risks.

Within the broader Anthropocene Epoch resides the Plasticene Era, where humans are subjected pervasively to nano- and microplastics (NMPs). Human's widespread exposure with NMPs occurs through the air we breathe, water we drink, and food we eat. NMP sources are wide and varied; atmospheric NMPs are largely attributed to fibres from car tyres and synthetic clothing, while particles from food packaging, personal care products, and plastic manufacturing contribute significantly to food and water contamination. NMPs have become inherent within the human body and have been found in every organ. As such, the evidence base around adverse health effects is fragmented but growing. This article presents a mini-review and report of sessions presented about NMPs at the 19th International Conference of the Pacific Basin Consortium for Environment and Health, held on Jeju Island, in 2022. Abundant evidence of substantial exposure to NMPs in the Asia-Pacific region has been exhibited. Addressing this issue necessitates the collaboration of policymakers, manufacturers, and researchers to develop safer alternatives and implement mitigation and remediation strategies. The ongoing development of a new United Nations-led global plastic treaty presents a crucial opportunity that must be acted on and not be compromised.

[Allergy and immunotoxicology in preventive and clinical medicine from theory to practice: Occupational allergy and isocyanate-induced asthma].

Genetic and environmental factors and their interactions cause diseases and deteriorate health (Genetic and Environmental Interaction). Exposure to environmental factors plays a major role in the deterioration of health in the workplace.Occupational asthma (OA) is a common disorder in the workplace. Approaches to OA are well described and discussed in "Japanese Guideline for Diagnosis and Management of Occupational Allergic Diseases" by the Japanese Society of Occupational and Environmental Allergy. According to the guideline, OA and work-aggravated asthma comprise work-related asthma, and OA can be further divided into two disease entities: sensitizer-induced OA and irritant-induced OA. The guidelines also describe diagnostic and therapeutic strategies for OA. Since a definitive diagnosis of OA requires a comprehensive decision based on a detailed interview on clinical symptoms related to employment status and clinical tests, including inhalation tests of suspected substances as needed, the possibility of OA should be considered as the first step toward diagnosis of the patient. Otherwise, OA may not be diagnosed. Therapeutic strategies include exposure avoidance, environmental arrangements in the workplace, utilization of social resources for workers, and conventional pharmacotherapy for asthma.Artificially synthesized small compounds are used in various industries and can cause allergies. For example, isocyanates are small compounds in the -NCO group, which have been toxicologically studied. It was later shown that isocyanate could cause various nontoxic adverse health effects, including allergic reactions. Since small agents with low molecular weights bind to proteins, detecting their specific immunoglobulin E (IgE) antibodies targeting small compounds is generally difficult. In contrast, isocyanate-specific IgE antibodies are detectable in individuals with isocyanate allergies.Suspecting OA is essential in cases exposed to newly synthesized compounds, or to those that are already known but applied to new uses, which can be better understood and predicted by studying the health effects of isocyanates.Academic interest in various issues related to allergies, immunology, and toxicology in the workplace includes clinical medicine, epidemiology, and epigenetics related to environmental exposure. Further advanced research in these areas is necessary and promising.

Lead In Food And Its Correlation With Blood Lead Levels Among Pregnant Women Of Sindh, Pakistan.

BACKGROUND: With increasing control of lead (Pb) in gasoline, food has emerged as an important secondary pathway for Pb exposure globally. This study assessed Pb levels in food duplicates and blood. Furthermore, it assessed the correlation of Pb in food duplicates and blood Pb levels with common food items taken by pregnant women of Sindh, Pakistan. METHODS: A cross-sectional study was conducted from August 2014 to November 2015, in urban (Karachi) and rural (Gambat, Khairpur) area of Sindh-Pakistan. A total of 103 venous blood samples (Karachi = 63 and Gambat = 40) of pregnant women were measured for blood Pb levels at the time of delivery. One month post-delivery, food frequency questionnaire (FFQ) was administered and three-day food duplicates (same number of cooked portions of food eaten by women) were collected. Food duplicates were analysed for Pb levels. Multivariable linear regression was conducted to identify the frequency of food items which contribute to blood and food Pb levels of pregnant women, separately. RESULTS: With 90% confidence interval, chapati (local flat bread) (ß=0.20, p<0.001), boiled rice (ß=0.35, p<0.001), cooked root vegetables (ß= 0.16, p=0.03), fried savory items (ß=0.15, p=0.03), sweet snacks (ß=0.13, p=0.08) were positively associated with elevated mother blood Pb levels. While cream biscuits (ß =-0.14, p=0.04), lassi (blend of yogurt, water and spices) (ß= -0.31, p<0.01), market milk desserts (ß=-0.22, p<0.001), fish (ß= -0.16, p=0.02), soft drinks (ß= -0.19, p=0.01) and supari/gutka (betel-nut) (ß=-0.13, p= 0.06) were negatively associated with mother Pb levels. Tetra-pak market juices (ß= 0.30, p<0.001) and cooked root vegetables (ß=0.19, p=0.05) were positively associated with mother food Pb levels, at 90% CI. CONCLUSIONS: Bread, boiled rice, fried savoury items, sweet snacks and cooked root vegetables were contributing to blood Pb levels of pregnant women in Pakistan. These food items may be contaminated with Pb during processing, packaging and storage. Inverse relation of Supari/gutka and soft drinks with blood Pb levels may be due its overall reduction in absorption capacity of the gut for nutrients. Objective individual food item analysis for Pb is warranted for further intervention.

Concentration of folic acid (FA) in serum of Japanese pregnant women.

Objectives Exposure to inorganic arsenic (iAs) is a world-wide health concern. We reported that Japanese children and pregnant women are exposed to moderate levels of iAs through food. Reducing iAs contamination from foods of high iAs is an important issue unique in Japan. Integrated iAs is methylated to less toxic organic forms, and S-adenosyl-L-methyonine (SAM), a common methyl-donor of DNA and histones, is utilized in this process. Chronic consumption of SAM by iAs metabolism due to exposure to iAs might alter the epigenetic modification of genome. The SAM biosynthesis pathway is dependent on folate cycle, and it is possible that ingestion of sufficient folic acid (FA) is protective to iAs induced toxicity. Methods In the course of our cross-sectional body burden analyses of Pb and iAs in Japanese children and pregnant women, termed "PbAs study", FA concentration in serum of 104 pregnant women was measured. Results Mean (±SEM) of serum FA concentration was 15.8 ± 1.3 (ng/mL). There are significant number of people showing very high FA (>30 ng/ mL), and large fraction of them were taking supplements daily. Conclusions These results suggested that level of FA ingestion of Japanese pregnant women is high for supporting normal fetal development.

Contribution of house dust contamination towards lead exposure among children in Karachi, Pakistan.

Lead exposure is associated with impaired neurodevelopment among children. House dust is recognized as one of the important secondary sources of lead exposure in children. We assessed the relationship between lead contamination in house dust and blood lead level in Pakistani children. We investigated lead contamination in house dust samples collected from 59 houses in Karachi, Pakistan. The lead content of house dust in Pakistan was relatively higher than that reported in previous studies. Weekly lead intakes from house dust were considerably higher among Pakistani children. In Pakistani children, 12% (7 of 58) showed lead intake values greater than the previous Provisional Tolerable Weekly Intake of lead. A correlation (Pearson's correlation = 0.37) was found between weekly lead intake from house dust and blood lead level in Pakistani children. In addition, blood lead levels were significantly higher in children with high lead intakes than in children with low and medium lead intakes. Thus, house dust is an important source of lead exposure in Pakistani children.

Exposure Assessment of Cadmium in Female Farmers in Cadmium-Polluted Areas in Northern Japan.

Akita prefecture is located in the northern part of Japan and has many cadmium-polluted areas. We herein performed an exposure assessment of cadmium in 712 and 432 female farmers in two adjacent cadmium-polluted areas (A and B, respectively), who underwent local health examinations from 2001-2004. We measured cadmium concentrations in 100 food items collected from local markets in 2003. We then multiplied the intake of each food item by its cadmium concentration in each subject to assess cadmium intake from food and summed cadmium intake from all food items to obtain the total cadmium intake. Median cadmium intake levels in areas A and B were 55.7 and 47.8 µg/day, respectively, which were both higher than that of the general population and were attributed to local agricultural products, particularly rice. We also calculated weekly cadmium intake per body weight and compared it to the previous provisional tolerable weekly intake reported by the Joint FAO (Food and Agriculture Organization)/WHO (World Health Organization) expert committee on food additives or current tolerable weekly intake in Japan of 7 µg/kg BW/week. Medians in areas A and B were 7.2 and 6.0 µg/kg BW/week, respectively. Similar estimated values were also obtained by the Monte Carlo simulation. These results demonstrated that the cadmium exposure levels among the farmers were high enough to be approximately the tolerable weekly intake.

Exploratory analysis of plasma cytokine/chemokine levels in 6-year-old children from a birth cohort study.

This study aimed to reveal a new dimension of allergy profiles in the general population by using machine learning to explore complex relationships among various cytokines/chemokines and allergic diseases (asthma and atopic dermatitis; AD). We examined the symptoms related to asthma and AD and the plasma levels of 72 cytokines/chemokines obtained from a general population of 161 children at 6 years of age who participated in a pilot birth cohort study of the Japan Environment and Children's Study (JECS). The children whose signs and symptoms fulfilled the criteria of AD, which are mostly based on questionnaire including past symptoms, tended to have higher levels of the two chemokine ligands, CCL17 and CCL27, which are used for diagnosis of AD. On the other hand, another AD-related chemokine CCL22 level in plasma was higher only in children with visible flexural eczema, which is one of AD diagnostic criteria but was judged on the same day of blood examination unlike other criteria. Here, we also developed an innovative method of machine learning for elucidating the complex cytokine/chemokine milieu related to symptoms of allergic diseases by using clustering analysis based on the random forest dissimilarity measure that relies on artificial intelligence (AI) technique. To our surprise, the majority of children showing at least any asthma-related symptoms during the last month were divided by AI into the two clusters, either cluster-2 having elevated levels of IL-33 (related to eosinophil activation) or cluster-3 having elevated levels of CXCL7/NAP2 (related to neutrophil activation), among the total three clusters. Future studies will clarify better approach for allergic diseases by endotype classification.

Oral exposure to lead for Japanese children and pregnant women, estimated using duplicate food portions and house dust analyses.

BACKGROUND: Lead is a toxic metal abundant in the environment. Consumption of food contaminated at low levels of lead, especially by small children and pregnant women, raises a health concern. METHODS: Duplicated food portions and drinking water were collected over 3 days from 88 children and 87 pregnant women in Shimotsuke, Tochigi, Japan. Participants were recruited in this study between January 2014 and October 2015. Dust was also collected from their homes. Lead concentrations were measured and consequent oral lead exposure levels were estimated for this population at high risk to environmental toxicants. Lead concentrations of peripheral and cord blood, taken from children and pregnant women, and were also analyzed. RESULTS: Lead concentrations in food, drinking water, and house dust were low in general. Oral lead exposure to lead was higher for children (Mean ± SEM; 5.21 ± 0.30 µg/kg BW/week) than in pregnant women (1.47 ± 0.13 µg/kg BW/week). Food and house dust were main sources of lead contamination, but the contribution of house dust widely varied. Means ± SEM of peripheral and cord blood lead concentrations were 0.69 ± 0.04 µg/dL and 0.54 ± 0.05 µg/dL, respectively for pregnant women and 1.30 ± 0.07 µg/dL (peripheral only) in children. We detect no correlation between smoking situations and blood lead concentration in pregnant women. CONCLUSION: We conclude that oral lead exposure levels for Japanese children and pregnant women were generally low, with higher concentrations and exposure for children than for pregnant women. More efforts are necessary to clarify the sources of lead contamination and reduce lead exposure of the population at high risk even in Japan.

Augmentation of cadmium-induced oxidative cytotoxicity by pioglitazone in renal tubular epithelial cells.

The aim of this study was to examine whether a peroxisome proliferator-activated receptor (PPAR)-γ agonist could affect cadmium (Cd)-induced cytotoxicity via the increased expression of megalin, one of the uptake pathways, using renal epithelial LLC-PK1 cells. The treatment with 1 µM Cd for 24 h was not cytotoxic; however, when the cells were pretreated with 0.1 µM pioglitazone for 12 h and then exposed to 1 µM Cd for 24 h, significant accumulation of Cd and cytotoxicity were detected, with an increase in megalin mRNA expression. In addition, pretreatment with pioglitazone significantly increased the Cd-induced generation of hydrogen peroxide and cell apoptosis. The augmented Cd-induced cytotoxicity and apoptosis on preincubation with pioglitazone were inhibited by prior treatment with GW 9662 (PPAR-γ antagonist). These findings suggest that a PPAR-γ agonist could augment Cd-induced oxidative injury and cell apoptosis, possibly dependent on the expression level of the uptake pathway.

Hijiki seaweed consumption elevates levels of inorganic arsenic intake in Japanese children and pregnant women.

Although exposure to inorganic arsenic is a health concern, especially in developing foetuses and children, dietary exposure levels among pregnant women and children have not been extensively studied in Japan. To address this shortcoming, we completed a 3-day duplicate diet study for 104 children and 101 pregnant women in two cities, Shimotsuke, Tochigi and Asahikawa, Hokkaido. The levels of intake of total and inorganic arsenic were estimated using the concentrations of total and inorganic arsenic in food and drinking water measured by inductively coupled plasma-mass spectrometry. Estimated intakes of total and inorganic arsenic were 8.46 ± 3.02 [µg/kg BW/week] and 1.74 ± 1.07 [µg/kg BW/week] in pregnant women and 20.07 ± 3.53 [µg/kg BW/week] and 8.46 ± 3.02 [µg/kg BW/week] in children, respectively. Weekly arsenic exposure per kg body weight was significantly higher in children than in pregnant women. Concentrations of total arsenic were generally very low in collected drinking water samples with a small number of exceptions, and drinking water was not considered as a major source of inorganic arsenic exposure in Japan. We found that total and inorganic arsenic intake were higher among frequent consumers of hijiki seaweed, in both pregnant women and children. Although rice and rice products that are staple foods of the Japanese have been reported to be major sources of inorganic arsenic exposure in Japan, our results indicate that hijiki consumption elevates levels of inorganic arsenic in Japanese children and pregnant women. More efforts are necessary to reduce the risk of exposure to inorganic arsenic in populations highly sensitive to environmental pollutants.

Regional differences in infant 25-Hydroxyvitamin D: Pilot study of the Japan Environment and Children's Study.

BACKGROUND: In recent years, a resurgence in the number of infants with vitamin D deficiency has been noted. In addition to seasonal differences in exposure to ultraviolet (UV) rays, regional differences in dietary habits and lifestyles may affect susceptibility to vitamin D deficiency. No studies have been conducted, however, on infants in multiple regions of Japan to determine the extent of differences in vitamin D status. METHODS: 25-Hydroxyvitamin D (25OHD) was measured on radioimmunoassay in 126 infants aged 2-4 years, who participated in the Pilot Study of the Japan Environment and Children's Study (JECS) by the Ministry of Environment of Japan. A multiple regression model with 25OHD level as the outcome variable, and season and region as explanatory variables, was generated. RESULTS: Both region and season during which infants participated in this study significantly affected 25OHD level (P = 0.0087 and <0.0001, respectively; Wald test). Reflecting decreased exposure to UV rays, infants who were examined in winter had lower 25OHD than those examined in summer. Infants from both Fukuoka Prefecture (33°N) and Kumamoto Prefecture (32°N), however, had lower 25OHD than those from Tochigi Prefecture (36°N), contrary to expectations given the extent of UV exposure. CONCLUSIONS: Regional differences in daily habits and/or environmental factors affect 25OHD level in Japanese infants. The JECS is expected to identify those factors to provide guidance on preventing infantile vitamin D deficiency.

The cardiac glycoside ouabain activates NLRP3 inflammasomes and promotes cardiac inflammation and dysfunction.

Cardiac glycosides such as digoxin are Na+/K+-ATPase inhibitors that are widely used for the treatment of chronic heart failure and cardiac arrhythmias; however, recent epidemiological studies have suggested a relationship between digoxin treatment and increased mortality. We previously showed that nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasomes, which regulate caspase-1-dependent interleukin (IL)-1ß release, mediate the sterile cardiovascular inflammation. Because the Na+/K+-ATPase is involved in inflammatory responses, we investigated the role of NLRP3 inflammasomes in the pathophysiology of cardiac glycoside-induced cardiac inflammation and dysfunction. The cardiac glycoside ouabain induced cardiac dysfunction and injury in wild-type mice primed with a low dose of lipopolysaccharide (LPS), although no cardiac dysfunction was observed in mice treated with either ouabain or LPS alone. Ouabain also induced cardiac inflammatory responses, such as macrophage infiltration and IL-1ß release, when mice were primed with LPS. These cardiac manifestations were all significantly attenuated in mice deficient in IL-1ß. Furthermore, deficiency of NLRP3 inflammasome components, NLRP3 and caspase-1, also attenuated ouabain-induced cardiac dysfunction and inflammation. In vitro experiments revealed that ouabain induced NLRP3 inflammasome activation as well as subsequent IL-1ß release from macrophages, and this activation was mediated by K+ efflux. Our findings demonstrate that cardiac glycosides promote cardiac inflammation and dysfunction through NLRP3 inflammasomes and provide new insights into the mechanisms underlying the adverse effects of cardiac glycosides.

Lead Exposure Assessment among Pregnant Women, Newborns, and Children: Case Study from Karachi, Pakistan.

Lead (Pb) in petrol has been banned in developed countries. Despite the control of Pb in petrol since 2001, high levels were reported in the blood of pregnant women and children in Pakistan. However, the identification of sources of Pb has been elusive due to its pervasiveness. In this study, we assessed the lead intake of pregnant women and one- to three-year-old children from food, water, house dust, respirable dust, and soil. In addition, we completed the fingerprinting of the Pb isotopic ratios (LIR) of petrol and secondary sources (food, house-dust, respirable dust, soil, surma (eye cosmetics)) of exposure within the blood of pregnant women, newborns, and children. Eight families, with high (~50 µg/dL), medium (~20 µg/dL), and low blood levels (~10 µg/dL), were selected from 60 families. The main sources of exposure to lead for children were food and house-dust, and those for pregnant women were soil, respirable dust, and food. LIR was determined by inductively coupled plasma quadrupole mass spectrometry (ICP-QMS) with a two sigma uncertainty of ±0.03%. The LIR of mothers and newborns was similar. In contrast, surma, and to a larger extent petrol, exhibited a negligible contribution to both the child's and mother's blood Pb. Household wet-mopping could be effective in reducing Pb exposure. This intake assessment could be replicated for other developing countries to identify sources of lead and the burden of lead exposure in the population.

External lead contamination of women's nails by surma in Pakistan: Is the biomarker reliable?

Adverse health effects of heavy metals are a public health concern, especially lead may cause negative health impacts to human fetal and infantile development. The lead concentrations in Pakistani pregnant women's nails, used as a biomarker, were measured to estimate the lead exposure. Thirteen nail samples out of 84 nails analyzed contained lead higher than the concentration (13.6 µg/g) of the fatal lead poisoning case, raising the possibility of an external contamination. Eye cosmetics such as surma are recognized as one of the important sources of lead exposure in Pakistan. We collected in Pakistan 30 eye cosmetics made in Pakistan, Saudi Arabia and western countries. As the metal composition analysis by energy dispersive X-ray fluorescence spectrometry revealed that some surma samples contained lead more than 96%, the surma might contaminate the nail specimen. Scanning electron microscopy observations showed that lead-containing surma consists of fine particle of galena (ore of lead sulfide) in respirable dust range (less than 10 µm). In addition, relative in vitro bioavailability of lead in the surma was determined as 5.2%. Thus, lead-containing surma consists of inhalable and bioavailable particles, and it contributes an increased risk of lead exposure. Moreover, the relationship between the surma and the lead-contaminated nails by lead isotope ratios analysis indicated the potential of lead contamination in nails by surma. These results suggest that lead in the nails was derived both from body burden of lead and external contamination by lead-containing surma. Therefore, nail is not suited as a biomarker for lead exposure in the countries where surma used, because we may overestimate lead exposure by surface lead contamination in the nail by surma.

Heavy metal exposure, in combination with physical activity and aging, is related with oxidative stress in Japanese women from a rural agricultural community.

This study aimed to evaluate the relationships between oxidative stress and heavy metal exposure (lead [Pb] and cadmium [Cd]), as well as co-factors such as physical activity and age, in Japanese women. This study was conducted with female subjects from a rural agricultural community in Japan. Subjects were asked to complete lifestyle-related questionnaires and undergo a group health examination. Physical activity, alcohol consumption, body mass index, and other demographic information were collected. Blood and urine samples were collected to measure urinary 8-hydroxydeoxyguanosine (8-OHdG) levels and blood and urinary Cd and Pb concentrations. Urine samples were analyzed using high performance liquid chromatography and flameless atomic absorption spectrometry; blood samples were analyzed using inductively coupled plasma-mass spectrometry. Age, physical activity, and blood and urinary Cd and Pb concentrations were included in structural equation modeling analysis. Two latent factors for heavy metal exposure and physical activity were produced to predict the total influence of the variables. The final model was good: CMIN/DF = 0.775, CFI = 1.000, GFI = 0.975, AGFI = 0.954, RMSEA = 0.000. 8-OHdG levels were positively associated with heavy metal exposure, physical activity, and age (standard ß of path analysis: 0.33, 0.38, and 0.20, respectively). Therefore, oxidative stress is associated with both, environmental and lifestyle factors, in combination with aging.

Exposure assessment of lead from food and airborne dusts and biomonitoring in pregnant mothers, their fetus and siblings in Karachi, Pakistan and Shimotsuke, Japan.

AIM: Exposure assessment of lead (Pb) and Arsenic (As) from food, water, and house dust intake were assessed among pregnant women, their children and fetuses in Pakistan and Japan, as well as their body burden of the metals in their blood. METHOD: Fifty families which included a pregnant woman, a fetus and the 1-3-year-old siblings were recruited in Karachi and Khairpur in Pakistan, and Shimotsuke and Asahikawa in Japan, respectively. Their dietary exposure to Pb and As was measured in 3-day food duplicates and drinking water by ICP-MP. Pb in house dust and respirable dust was evaluated with an energy dispersive X-ray fluorescence spectrometry. Non-radioactive isotope Pb profiles of blood specimens will be compared with those of the exposure origins, such as food duplicates, respirable house dust, the soils nearby, and gasoline. RESULTS: Judging from the data collected and analyzed so far, contribution from dietary intake is highly correlated to higher body burden of Pb among Pakistani mothers. Additional data analyses will reveal the status of Pb and As body burden in Pakistani mothers, fetuses and their siblings, and causal sources of high body burden is delineated by Pb isotope profile analysis of different sources of Pb exposure.

Relieving pain and distress during venipuncture: Pilot study of the Japan Environment and Children's Study (JECS).

Pain management for needle-related procedures is poor in Japan. In many countries the use of lidocaine/prilocaine cream for the relief of pain associated with venipuncture has been approved. In children, a psychological approach has also been shown to be effective in reducing pain with venipuncture. We developed a multidisciplinary procedure that combines a cream (2.5% lidocaine and 2.5% prilocaine) and pharmacological approaches such as preparation, education, positioning and distraction. We evaluated the feasibility and acceptability of the procedure for young children. Among 132 pediatric participants, 58.3% did not cry during venipuncture. According to caregiver questionnaire, 71.9% felt that the multidisciplinary procedure eliminated the fear of needle-related procedures in the children; 90.9% were satisfied with it and 75.8% thought it should be applied to all children undergoing venipuncture. The present results suggest that the multidisciplinary procedure is feasible, acceptable and suitable for use in children undergoing venipuncture.

A study of the association between urinary aluminum concentration and pre-clinical findings among aluminum-handling and non-handling workers.

BACKGROUND: Aluminum is considered to be a relatively safe metal for humans. However, there are some reports that aluminum can be toxic to humans and animals. In order to estimate the toxicity of aluminum with respect to humans, we measured the aluminum concentration in urine of aluminum-handling and non-handling workers and investigated the relationships between their urinary aluminum concentrations and pre-clinical findings. METHODS: Twenty-three healthy aluminum-handling workers and 10 healthy non-aluminum-handling workers participated in this study. Their medical examinations, which were otherwise unremarkable, included the collection of urine and blood. Urinary aluminum levels were analyzed using ICP analysis. As pre-clinical tests, we measured KL-6, SP-D, TRCP-5b, IL-6, and IL-8 in blood and δ-ALA and ß2-microglobulin in urine. These were considered to be lung, bone, kidney and inflammation markers. Moreover, we measured 8-OHdG in urine as an oxidative DNA damage marker. RESULTS: The aluminum concentration in urine ranged from 6.9 to 55.1 µg/g cre (median: 20.1 µg/g cre) in the aluminum-handling workers and from 5.6 to 15.6 µg/g cre (median: 8.8 µg/g cre) in the non-aluminum-handling workers, with a significant difference between them. In the pre-clinical findings, there were no significant differences between these two groups except in the case of δ-ALA. However, there were no significant relationships between aluminum concentration and the pre-clinical findings, work years, age or 8-OHdG in the aluminum-handling workers. CONCLUSIONS: While the excretion of aluminum in urine was elevated in aluminum-handling workers, our findings suggest that low-dose aluminum is not directly harmful to humans, at least when workers' urinary aluminum concentration is below 55 µg/g cre.