The demand for safe and sanitary drinking water is a basic human right worldwide (
1,
2). According to the World Health Organization (WHO), nearly 29% of the global population does not have access to water free from contamination. Several contaminants can pollute drinking water such as toxic substances, microbial contaminants (bacteria and viruses), and chemical compounds (
3). The levels of contamination in drinking water are influenced by the quality of the water sources, used tanks for water storage, water distribution systems, pipe corrosion, and household filters. In industrial development areas, many health problems can be caused by exposure to heavy metals (
4,
5).
Owing to the non-biodegradable and bioaccumulation properties of heavy metals, their levels can increase in living organisms during life, which affects the function of the organs. There are some mechanisms assumed for heavy metals that may lead to neurotoxicity, the free radical generation which promotes oxidative stress, damaging lipids, proteins, and DNA molecules, and also propagating carcinogenesis (
6). These elements enter water resources through industrial activities such as surface water collection, agricultural wastewater, burning fossil fuels, industrial wastewater, mining, and transportation (
7-
9) or natural ways such as rainfall and soil erosion, and the dissolution of soluble salts (
10,
11). Some heavy metals are known to have carcinogenic effects on signaling proteins or cellular regulatory proteins responsible for apoptosis, DNA repair, DNA methylation, cell cycle regulation, and growth. The redox-sensitive transcription factors such as AP-1 can be activated through the recycling of electrons by the antioxidant network, which may be another carcinogenic effect of certain heavy metals. These transcription factors have a key role in controlling the expression of gene, which are protective against apoptosis, prevent the damage of cells, repair DNA, and strengthen the immune system (
12-
15). Contamination of water with toxic metals could cause morphological disorders, growth retardation, higher mortality, carcinogenicity and genetic adverse effects in humans (
10,
13,
14). Cadmium (Cd) could accumulate in many organs with a long half-life of about 10 to 30 years (
16), which causes many disorders such as different types of cancer in the kidney, pancreas, nasopharynx, prostate, lung, and breast cancers (
17). Also, the most sensitive organs to Cd are the liver and kidneys by their ability to synthesize Cd-inducible proteins (metallothioneins) (
18). Lead is a neurotoxin that is responsible for many metal poisonings in humans, and it may block hemoglobin production, reproductive system and circulatory system failure, and acute and chronic damage to the central nervous system (
9,
14,
19). Mercury exists in forms of elemental, organic, and inorganic in the environment and all forms have cytotoxic effects (
20). People are exposed to elemental mercury through artisanal gold mining and dental amalgam restorations, which can remain in the brain and lead to neurological symptoms (
15,
21). Chromium is a silver-colored hard metal with different states of oxidation from +6 to −2. Trivalent (Cr
+3) and hexavalent (Cr
+6) chromium are the most stable oxidation states of chromium and have toxic effects on microorganisms, plants, animals, and humans (
22). Chromium is harmful to health at high concentrations and can cause lung and intestinal cancers, nasal mucous ulcers, stomach distress, nephritis, and liver damage, especially Cr
+6 (
23). Therefore, Cr
+6 is considered a hazardous ion with high solubility in soil and water and animals; carcinogenic effects were determined when ingested drinking water was polluted with Cr
+6 (
24,
25). Copper is rarely found in natural waters; hence, its presence at high concentrations is an indicator of water pollution through municipal or industrial wastewater (
9). Heavy metals contaminated waters have led to a high global toxicity, morbidity, and mortality and the common mechanism of them is the production of reactive oxygen, and the oxidative damage endangers the health of consumers (
26).
The cancer incidence, deaths, and death rate resulting from heavy metals exposure by drinking water at the national level were calculated as 213 (95% uncertainty interval: 180 to 254), 87 (73 – 104), and 0.11 (0.09 – 0.13), respectively. Skin cancer had the highest cancer incidence (121 cases); however, because of the high survival rate, the skin cancer share in the attributable deaths was 12.2%. Lung cancer was responsible for the highest share of the attributable burden of disease. The cancer cases, deaths, and death rate raised from exposure to heavy metals in drinking water were, respectively, 73 (59 – 91), 27 (22 – 33), 0.13 (0.10 – 0.18), in rural and 139 (104 – 190), 60 (45 – 82), 0.10 (0.08 – 0.14), in urban areas (P < 0.05). In the country, the order of heavy metal ILCRs was as As, Cd, Cr, and Pb, respectively. Cd had the role in about two-thirds of the imputable burden of diseases. The prevalence rate of skin cancer in Newfoundland and Labrador, Canada from 2008 to 2017 by exposure to As through drinking water was 363 to 449 cases per 100 000 people. In Shanghai, the average Cd intakes from 1988 to 97, 1998 to 2007, and 2008 to 2018 were 39.7, 44.7, and 36.4 mg/d, respectively. Annual cancer cases attributed to As exposure in Ontario, Canada was estimated to be 120 (20 – 370) (
27).
Planning the ongoing programs about health risk assessments of heavy metals is necessary during a lifetime. Health risks (non-carcinogenic and carcinogenic) are to estimate the possibility of illness and death caused by exposure to pollutants such as heavy metals, which are dependent on dose, duration, and exposure level (
28). Cancer risks are associated with exposure to carcinogenic toxic metals over a lifetime (
29).
Therefore, due to the tendency of heavy metals to accumulate in the body cells and their toxicities, the risk assessments of human exposure to these contaminants through the intake of drinking water are very crucial. Drinking water is the main route of these contaminants' entrance to the human organs.