Adverse Health Effects in Children due to Arsenic Exposure, B. Windham (Ed.)
The toxic metals lead, mercury, and arsenic are the top 3 toxics having the most adverse health effects on the public based on toxicity and current exposure levels in the U.S. (1) Arsenic, like most of the other metals has been found in studies to be associated with neurologic, cardiovascular, dermatologic, immune, endocrine (diabetes), hepatic, and carcinogenic effects, along with reproductive effects (24,25,26,1b,3,16,18,20, 36-38,40,43etc.); and according to U.S. DOH affects more people than any other toxic substance (1a). Long-term exposure to ingested arsenic has been documented to induce peripheral vascular disease, cartoid arteriosclerosis, ischemic heart disease, and cerebral infarction in a dose-response relationship (24a,1b). A comparison of areas with higher levels of arsenic in the water supply found higher fetal and infant mortality in areas with higher arsenic levels and higher cancer rates. Some of the developmental effects documented to be caused by low level toxic metal exposure include developmental delays, growth problems, slower reaction times, diminished intellectual ability, behavior problems, poor balance and motor function, hearing loss, attention deficit disorder, peripheral neuropathy, etc. (19,30,24,25,26,1b,16,18,34,36-38,40, etc.)
A comprehensive analysis of published data indicates that arsenic exposure induces cardiovascular diseases (43), developmental abnormalities, neurologic and neurobehavioral disorders, diabetes, hearing loss, hematologic disorders, and various types of cancer (34,41,42). Recent reports have pointed out that arsenic poisoning appears to be one of the major public health problems of pandemic nature. Acute and chronic exposure to arsenic has been reported in several countries of the world where a large proportion of drinking water (groundwater) is contaminated with high concentrations of arsenic. Research has also pointed significantly higher standardized mortality rates for cancers of the bladder, kidney, skin, liver, and colon in many areas of arsenic pollution (34,41,42). Arsenic is often found at high levels in drinking water (34b,36).
Several studies have found Arsenic to be significantly associated with type 2 diabetes and other conditions (36). Total urine arsenic was associated with increased prevalence of type 2 diabetes, and since there is a widespread exposure worldwide this finding supports the hypothesis that low levels of exposure to inorganic arsenic in drinking water may play a role in diabetes prevalence (36a). Arsenic multifactorial effects include accelerating birth and postnatal weight gains, elevated body fat content, glucose intolerance, insulin resistance, and increased serum lipid profile. Arsenic also elevated cord blood and placental, as well as postnatal serum leptin levels. The data from human studies indicate an association between inorganic arsenic exposure and the risk of diabetes and obesity (36c). A study also found polymorphisms in diabetes- related genes to be a factor in toxic effects (36b).
Combinations of toxic metals have synergistic effects that are associated with type 2 diabetes and other conditions (37). Associations between arsenic and cadmium were reported for cardiovascular and kidney disease, type I and type II diabetes, cognitive function, hypothyroidism, and increased prevalence and mortality for lung and other cancers (37,38,41,42,43). Studies have found Arsenic can cause several forms of cancer including Lung cancer, Bladder cancer, Skin cancer, lung, digestive tract, liver, kidney, tract, urothelial, lymphtic , and hematopoietic systems (44,45).
Study results demonstrated that As and Cd exposure caused significant changes to the gut microbiome and metabolome by affecting bile acids, amino acids and taxa associated with metabolic health (37c). Inorganic Arsenic can increase DM risk by impairing mitochondrial metabolism, one of the key steps in the regulation of glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells (36) . The results also found that Manganese, like Arsenic, may inhibit GSIS by impairing mitochondrial function, whereas Cd may target other mechanisms that regulate GSIS in β-cells. Impairment of hepatic glucose homeostasis can also play a crucial role in the pathogenesis of DM. Along with compromised function of pancreas and muscles, diminished liver and kidney functions also contribute considerably to increase the blood glucose level. These metals have potential to bring conformational changes in these enzymes and make them inactive. Additionally, these metals also disturb the hormonal balance, such as insulin, glucocorticoids and catecholamines; by damaging pancreas and adrenal gland, respectively. Moreover, these metals also enhance the production of reactive oxygen species and depress the anti-oxidative defense mechanism with subsequent disruption of multiple organs (37). Exposure to Endocrine Disrupting Chemicals ( EDCs ) during fetal or early life can disrupt the development of both the immune system and the pancreatic beta cells, potentially increasing susceptibility to T1DM later in life. In addition, developmental exposure to some EDCs can affect beta cell development and function, influencing insulin secretion. These changes may increase stress on the beta cells and identify them as a target to the immune system. Developmental exposure to EDCs that disrupt metabolism by increasing insulin resistance or obesity may also stress the beta cells. (38,37,36).
�Developmental exposure to some EDCs can cause immune system dysfunction, increasing the risk of autoimmunity (37). Arsenic is on the EPA Special Health Hazard List because it is a potent Class A carcinogen in humans (3,31), as well as being neurotoxic. An EPA study of cancer incidence for different levels of arsenic in drinking water found a dose related response for all types of cancer (31). The cancer rate for people with drinking water levels of above .6 parts per million arsenic were approx. 3 times those for people drinking water below .3 ppm arsenic, with large increases in cancers of internal organs. According to U.S.EPA it also causes birth defects, learning disabilities, damage to bone marrow, and other health problems, and new studies estimate that drinking water contaminated with arsenic at the current federal limit poses a 1 percent lifetime risk of cancer- about the same as radon or tobacco smoke (3). EPA staff have proposed lowering the drinking water standard for arsenic substantially from 10 ppb to 5 parts per billion.
Arsenic is often found at high levels in coastal and estuarian water bodies. The metalloids arsenic, selenium, and tellurium can be converted to volatile products of extreme toxicity (31,32). Arsenic is acutely toxic to marine organisms but also has other effects at lower levels including growth retardation and reproductive failure (33, etc.). Arsenic is widely distributed in sediments in some areas of Florida and bioaccumulates in the food chain. The FDEP NOEL (no observed effect level) for arsenic is 8 ppm. The FDEP sediment PEL is 64 ppm. The EPA contaminant criteria (33c) for arsenic in seafood is 2 ppm. The drinking water standard is 10 ppb.
The toxic metals most dangerous to people eating fresh- water fish are those that accumulate in the edible muscle of fish‑ including mercury, arsenic, radioactive cesium, and to a lesser degree lead (31). Shellfish, especially oysters, accumulate lead, mercury, cadmium, copper, silver, arsenic, and radioactive metal isotopes (31). Oysters and other shellfish are accumulating increasing amounts of toxic metals, with oysters often accumulating levels of cadmium, lead, and arsenic dangerous to people and above the FDA recommended action level or guideline level (59).
While there is no FDA Action Level for arsenic, arsenic is more acutely toxic than the other metals for which there is an action level and arsenic is highly carcinogenic (1,3,31). The drinking water guideline for arsenic is lower than those for mercury or cadmium- 10ppb. The EPA toxics contaminant criteria for arsenic in seafood is 2 ppm (33c).
Arsenic accumulates in shellfish and has been found at levels 20 times the EPA guideline maximum contaminant level (19.9). The toxic arsenite form is the primary form in shellfish and the most toxic form to people.
Utilities and incinerators are the largest source of mercury, cadmium, arsenic, chromium, and manganese emissions in the U.S. (32,3). Fossil fuel combustion is also responsible for over 90% of nickel and beryllium emissions. Midwestern coal, especially Missouri and Illinois, have very high levels of cadmium, nickel, and lead. Gulf Coast coal is high in most trace metals. Coal from northern Appalachia is high in arsenic, as well as mercury.
. Most coal ash laboratory tests have found cadmium and arsenic at levels considered hazardous per EPA RCRA standards, The high PH that often characterizes Western coals tends to cause the release of harmful toxic metals such as arsenic, selenium, and manganese.
According to an EPA/ATSDR assessment, the toxic metals lead, mercury, and arsenic are the top 3 toxics having the most adverse health effects on the public based on toxicity and current exposure levels in the U.S. (1), with cadmium, chromium and nickel also highly listed. Water, soils, and shellfish are common sources of exposure (3), but the most common and significant exposure to children is from pressure treated lumber in playgrounds and patios (2,4). Renee Sharp, principal author of a recent study involving tests of children stated that the study found that: "In two weeks, an average five-year-old playing on an arsenic-treated playset would exceed the lifetime cancer risk considered acceptable under federal pesticide law." (2) In recent months, dozens of public playgrounds in Florida have been closed after detection of high levels of arsenic. Some case histories of children with arsenic related neurological conditions with exposure mostly through treated lumber are found in (18). Eating chicken has also been found to be a significant source of arsenic exposure, since farmers feed arsenic to chickens and pigs to prevent parasites that are prevalent in crowded conditions (22).
Many similar studies measuring child hair levels of the toxic metals- aluminum, arsenic, cadmium, lead, and mercury have found that these toxic metals have significant effects on learning ability and cognitive performance, explaining as much as 20 % of cognitive differences among randomly tested children who have low levels of exposure not exceeding health guidelines for exposure to any of these metals (6-15,17,19). These toxic metals have been found to have synergistic negative effects on childhood development and cognitive ability (8,13-15,21).
A study (35) of Uruguayan school children found that arsenic concentrations were positively associated with 8-OHdG concentrations, a marker for oxidative stress. In sum, even at low-level, Arsenic exposure is associated with detectable oxidative damage to the DNA.
These toxic metals have also been found to have significant effects on motor-visual ability and performance (6a,8,19,20,30,40), as measured by the Bender Visual-Motor Gestalt Test score. Arsenic, lead, and cadmium levels had the highest correlation with cognitive scores, while aluminum had a significant relation mostly with motor-visual performance and mercury had lesser but highly significant correlations to both. A combined hair level score for mercury, lead, arsenic, cadmium and aluminum was found to be significantly related to increased scores on the WPBIC subscales measuring acting-out, disturbed peer relations, immaturity, and the total score (6) among a population of students with no known acute exposures.
Chronic exposure to arsenic at very low levels (below 10 parts per billion) have been found to cause cancer by a review by the National Academy of Sciences (23) and other studies (2,5). Two industry funded studies supported causality of cancer in workers (5). The first concluded that arsenic exposure was related to an increased risk of respiratory cancer in Tacoma Smelter workers in every category of exposure(5a). The second study, conducted by University of Michigan scientists, confirmed a previously established relationship between arsenic exposure and lung cancer in Anaconda Smelter workers(5b). A Univ. of Washington study found that those with significant arsenic exposure have more than double the normal incidence of Parkinson's (27).
Common sources of arsenic include wood preservatives (2), antibiotics given to commercial livestock, air pollution, chemical processing, coal-fired power plants, defoliants, drinking water, drying agents for cotton, fish and shellfish, herbicides, insecticides, meats (from commercially raised poultry and cattle), metal ore smelting, pesticides, seafood (fish, mussels, oysters), and specialty glass.
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Prolonged ingestion of arsenic-containing drinking water is associated with an increased risk of bladder cancer and skin cancer , and medical exposure to arsenic has been clearly associated with skin cancer in epidemiological studies. In addition, cancers of the lung , digestive tract, liver , kidney , and lymphatic and hematopoietic systems have been linked to arsenic exposure . ; & (c ) Arsenic Exposure and Risk of Urothelial Cancer: Systematic Review and Meta-Analysis , Int J Environ Res Public Health, 2020 Apr 29;17(9):3105.
[Arsenic metabolites are significantly associated to urothelial cancer.]