Clinical Pharmacist and Master’s student in Clinical Pharmacy with research interests in pharmacovigilance, behavioral interventions in mental health, and AI applications in clinical decision support. Experience includes digital health research with Bloomsbury Health (London) and pharmacovigilance practice in patient support programs. Published work covers drug awareness among healthcare providers, postpartum depression management, and patient safety reporting. 
Clinical Pharmacist and Master’s student in Clinical Pharmacy with research interests in pharmacovigilance, behavioral interventions in mental health, and AI applications in clinical decision support. Experience includes digital health research with Bloomsbury Health (London) and pharmacovigilance practice in patient support programs. Published work covers drug awareness among healthcare providers, postpartum depression management, and patient safety reporting. What was reviewed?
This article examined the epidemiological and biochemical evidence linking chronic arsenic exposure to various non-malignant health outcomes across three countries with differing exposure histories. The authors synthesized data from Taiwan, where arsenic-induced “black foot disease” emerged as a severe vascular disorder; Chile, where long-term follow-up studies revealed persistent cardiovascular, diabetic, and pulmonary effects decades after exposure ceased; and Bangladesh, where ongoing contamination provided opportunities for biomarker-based mechanistic studies. The review focused on the biochemical pathways by which arsenic induces oxidative stress, endothelial dysfunction, and inflammatory responses leading to hypertension, diabetes mellitus, and cardiovascular and respiratory diseases. Special emphasis was placed on Bangladeshi studies that identified dose-dependent changes in disease-related biomarkers such as big endothelin-1, oxidized LDL, CRP, soluble adhesion molecules, and Th2 cytokines, providing molecular-level insight into arsenic’s chronic toxicological impacts on vascular, metabolic, and immune systems relevant to heavy metal health standards and certification frameworks.
Who was reviewed?
The populations reviewed encompassed diverse exposure contexts: Taiwanese residents consuming artesian well water with arsenic concentrations averaging 780 μg/L for over three decades, Chilean residents of Antofagasta exposed to 860 μg/L arsenic in municipal water between 1958–1970, and Bangladeshi rural populations exposed to 150–1000 μg/L arsenic through groundwater and rice irrigation. Collectively, more than 200 million individuals worldwide are affected by similar exposures exceeding the WHO limit of 10 μg/L. The Bangladeshi cohorts—particularly from Araihazar and Matlab under the Health Effects of Arsenic Longitudinal Study (HEALS)—provided robust cross-sectional and longitudinal datasets linking biomarker responses to real-time exposure, in contrast to the historical epidemiological data from Taiwan and Chile. Participants typically had low BMI, minimal alcohol or tobacco use, and lived in socioeconomically homogenous environments, which minimized confounding and strengthened associations between arsenic dose and disease endpoints. This multi-country comparison offered a unique opportunity to examine both acute and chronic exposure effects across age, sex, and metabolic profiles.
Most important findings
| Critical Points | Details |
|---|---|
| Cardiovascular and vascular pathology | Chronic arsenic exposure promotes endothelial damage, increases oxidative stress, and elevates vascular biomarkers such as big endothelin-1, oxidized LDL (OxLDL), C-reactive protein (CRP), and adhesion molecules (sVCAM-1, sICAM-1). These effects lead to atherosclerosis, hypertension, and endothelial inflammation. Arsenic activates NADPH oxidase (NOX2) and lectin-like oxidized LDL receptor (LOX-1), reinforcing ROS generation and monocyte adhesion, which contribute to plaque formation and vascular occlusion. |
| Metabolic disruption and diabetes mellitus | Arsenic exposure elevates fasting blood glucose and insulin resistance (HOMA-IR) without direct pancreatic damage. Evidence from Bangladesh suggests arsenic-induced skeletal muscle atrophy (reflected by decreased serum creatinine and lean body mass) impairs glucose uptake, promoting insulin resistance. Females exhibited higher susceptibility to hyperglycemia. |
| Biomarker alterations | Dose-dependent increases were documented in big endothelin-1, VEGF, MMP-2/9, uric acid, soluble thrombomodulin (sTM), and Th2 cytokines (IL-4, IL-5, IL-13, eotaxin). HDL decreased while oxidized LDL increased, reflecting lipid peroxidation and impaired vascular repair. These biomarkers form a mechanistic chain linking oxidative injury to systemic inflammation and vascular remodeling. |
| Respiratory dysfunction and immune modulation | Spirometric tests showed reduced FEV1 and FEV1/FEV6 ratios among Bangladeshi subjects, indicating obstructive lung disease consistent with asthma-like symptoms. Elevated IgE and Th2 cytokines confirmed a Th2-dominant immune response, implicating arsenic in allergic-type asthma pathogenesis. |
| Cross-country epidemiology | Taiwanese “black foot disease” exemplified high-dose, long-duration vascular pathology; Chilean cohorts demonstrated delayed disease manifestation after early-life exposure; and Bangladeshi cohorts provided current mechanistic data via biomarkers. Together, these findings established a global continuum of arsenic toxicity outcomes. |
Key implications
The findings underscore arsenic’s role as a multi-system toxicant, highlighting the need for stringent heavy metal certification and monitoring standards under programs like HTMC. Regulatory bodies must incorporate biomarker-based assessments—especially big endothelin-1, OxLDL, and Th2 cytokine profiles—to detect early subclinical impacts. Certification protocols should address cumulative exposure from both water and food sources, particularly rice in arsenic-affected regions. For industry application, these insights call for advanced testing technologies in food and water safety certification, alongside inclusion of immunological and metabolic indicators in compliance benchmarks. Research gaps remain in understanding gender-specific vulnerability, long-term reversibility of arsenic-induced changes, and synergistic effects with obesity. Practically, routine biomarker surveillance and community-level education programs are recommended for sustainable risk mitigation.
Citation
Himeno S, Hossain K. Non-malignant diseases associated with environmental arsenic exposure in Taiwan, Chile, and Bangladesh.Metallomics Research. 2021;1:#MR202109. doi:10.1234/mr202109.
Arsenic is a naturally occurring metalloid that ranks first on the ATSDR toxic substances list. Inorganic arsenic contaminates water, rice and consumer products, and exposure is linked to cardiovascular disease, cognitive deficits, low birth weight and cancer. HMTC’s stringent certification applies ALARA principles to protect vulnerable populations.
