Neurotoxicity: Arsenic

Arsenic is a naturally occurring metalloid element in the earth’s crust, which has, in the past 100 years, been used in pesticides, chemotherapeutic agents, and certain consumer products. Since the Middle Ages or earlier, it has been noted as a powerful poison to humans (Hughes et al. 2011). While individuals can be exposed to arsenic in the air and in food, the greatest human health threat from arsenic is in exposure through drinking water. Local geology plays a major factor in the levels of arsenic compounds in drinking water, and as such, these levels can vary greatly between locations (Smedley and Kinniburgh 2002).

While this section discusses the neurotoxic effects of arsenic exposure in children, arsenic exposure has been associated with cancer, reproductive effects, cardiovascular disease, cerebrovascular disease, and diabetes (Smith and Steinmaus 2011; Navas-Acien 2008).

Background Information

Arsenic can form inorganic arsenic compounds in the environment and organic arsenic compounds in organisms (ATSDR 2007). Inorganic arsenic in compounds exists in one of two oxidation states—trivalent and pentavalent; trivalent arsenic is more toxic than its pentavalent counterpart, and is the dominant form used in most industrial processes. The once-held notion that organic arsenic compounds that occur in nature are less toxic than inorganic arsenic compounds has been found not to be entirely true. For example, certain organic arsenic compounds which have been developed as pesticides are highly toxic to humans and animals (Hughes 2002; AAP 2003).

When exposed, humans are capable of metabolizing inorganic arsenic in their bodies by methylating it to monomethylarsenate, dimethylarsenate, or trimethylarsenate. These are generally less toxic than inorganic arsenic, although trivalent methylated forms are more toxic than previously thought. However, children are less capable of methylating arsenic (the body’s process for metabolizing/processing inorganic arsenic to organic arsenic), than adults. As such, they are more likely to carry greater relative body burdens of inorganic arsenic for longer periods of time after the initial exposure (AAP 2003). Furthermore, there is strong evidence that early life exposures to arsenic, especially fetal exposures, can have long-term health effects which can last into adulthood (Vahter 2008).

Sources of Arsenic

Arsenic occurs naturally in the earth in discrete areas within bedrock called veins. Because there is variation in the amount and size of these veins, distribution of arsenic across the world is not uniform. Areas with little arsenic contamination may be in close proximity to areas with very high concentrations of arsenic (AAP 2003). Groundwater running through these veins can be contaminated, carrying high concentrations of arsenic in it. This is particularly a potential hazard with untreated well water. Once in the groundwater, arsenic may be expelled into the ocean where it can be ingested by marine life and incorporated into the food chain (AAP 2003).

In addition to natural occurrences, arsenic can be released from anthropogenic (man-made) sources such as fossil fuel combustion, smelter operations, and from its usage in pesticides (Smedley and Kinniburgh 2002; Hughes et al. 2011). In total, anthropogenic sources are estimated to account for approximately 70% of the global arsenic flux (Smedley and Kinniburgh 2002).

Arsenic has been used in many industrial processes. Due to its nearly universal toxicity in some forms, arsenic has been heavily relied upon as a pesticide and as an antimicrobial. Although the U.S. EPA banned most arsenical pesticides in 1991, chromatedcopper arsenate (CCA),an arsenic-based wood preservative used in pressure-treated wood to prevent insect damage and thus the accelerated decay of wood, was only prohibited for residential usage effective in 2004 (EPA 2011). The compound is 22% arsenic by weight, and a 12-foot section of pressure-treated wood could contain an ounce of arsenic (AAP 2003); furthermore, the wood ash from burned CCA treated wood can be up to 36% arsenic by weight (Solo-Gabriele et al. 2002).

Arsenic is also used as a semiconductor in place of silicon (gallium arsenide); can be used in petroleum refining and mining/smelting; and is sometimes found in alternative and herbal medicines. Due to its ability to enter groundwater and its widespread use in pesticides and for a variety of industrial purposes - both past and present, arsenic is widely distributed in the environment (AAP 2003).

Childhood Exposure to Arsenic in the United States

The major concern regarding arsenic exposure in the United States is that of contaminated drinking water. Prior to 2002, the U.S. EPA drinking water maximum contaminant level was 50 parts per billion (ppb); during 2002, the level was lowered to 10 ppb, with regulated water systems being required to meet the new standard by 2006; the lowering of this level was a result of new research demonstrating greater neurotoxic and carcinogenic risks from chronic arsenic exposure (MDEQ 2003). Children who get their drinking water from unprocessed well water, as well as some smaller local water systems, are more likely to be exposed to arsenic than those who get their drinking water from larger water treatment plants; however, even these larger plants have been found to leave residual arsenic in the effluent, depending on the treatment process used (AAP 2003). For infants, breastfeeding can limit arsenic exposure compared to bottle feedingwith formula using local water, as there is a limited transfer of arsenic in the mother’s breast milk (Vahter, 2008).

Children can also be exposed to arsenic through wood treated with chromated copper arsenate (CCA). Most decks, playgrounds, and picnic tables constructed before 2003 were built with pressure-treated wood containing the CCA mixture (EWG 2001, EWG 2007). Some data suggest that arsenic, long used in pressure-treated lumber, can leach from the lumber over time, exposing children to the toxicant (Khan et al, 2006). In 2001, an analysis by the Environmental Working Group of lumber purchased from major retailers showed that up to 1,020 micrograms of arsenic leached from commercial wood onto a small, wet cloth, an amount more than ten times the 10 ppb (µg/L) allowed by the EPA’s maximum contaminant level for drinking water (EWG 2007). A study by the EPA and the Consumer Product Saftey Commission found that the yearly application of penetrating stains or coatings to wood decks and other CCA-treated structures can reduce exposure to arsenic from the treated wood (EPA 2007).

Children can also be exposed to arsenic during outdoor play in soil from past pesticide use—or from mining and hazardous waste sites. Additionally, contamination of clothing can occur from occupational exposures and can result in arsenic being brought into the home.

Arsenic may also be present in food, and for people that don’t have high levels of arsenic in their domestic water supply, diet is the largest source of exposure to arsenic (ASTDR 2006). Despite current bans on most arsenical pesticides, crops may be contaminated with arsenic through residual exposure, inadvertent use of arsenical pesticides, or misuse of such pesticides (AAP 2003). According to a study by the Institute for Agriculture and Trade Policy (IATP), fish, rice and chicken are among the foods in the U.S. most likely to contain arsenic (IATP 2006). In the U.S Food and Drug Administration (FDA) Total Diet Study, which was conducted from 1991 to 1997, the foods with the highest levels of arsenic were (in descending order): seafood, rice/rice cereal, mushrooms, and poultry (ASTDR 2006).

Although arsenic can be present in high levels in seafood, it does not biomagnify through the food chain as other heavy metals can (ex. mercury). It is generally accepted that approximately 85-90% of the arsenic in edible portions of seafood is organic.

Rice is more efficient at accumulating arsenic into its grains than other cereal crops, in part due to the physiology of the plant, and in part because it is generally grown in flooded conditions, making arsenic in the soil more available to the plants (Bhattacharya et al. 2011). Rice may be an important source of arsenic exposure. A study of 229 pregnant women in the United States found that women whoate more rice had higher concentrations of inorganic and organic arsenic in their urine (Gilbert-Diamond et al., 2011). This may be of concern for weaning infants who are fed rice-based baby-food, especially those with celiac disease, as rice is a gluten-free source of carbohydrates. As a result, infants with celiac disease may be exposed to elevated levels of arsenic (Carbonell-Barrachina qet al. 2011). It may be best for children and adults with celiac disease to vary sources of gluten-free carbohydrates.

The Institute for Agriculture and Trade Policy, in a 2006 report, noted that inorganic arsenic residues in chicken meat result from the decades-old practice of intentionally adding organic arsenic to chicken feed as a growth stimulant. IATP estimates that at least 70 percent of the 8.7 billion American broiler chickens produced each year have been fed arsenic. Some of that arsenic is still in the chicken when it reaches American dinner tables. IATP estimates that between 1.7 and 2.2 million pounds of Roxarsone, a single arsenic feed additive, were given each year to chickens. Broad FDA labels have claimed that arsenicals are “For increased rate of weight gain, improved feed efficiency, and improved pigmentation.” In some cases, arsenic additives have also been labeled as an “…aid in the prevention of coccidiosis’” – an intestinal infestation caused by a parasite (IATP 2006). As of June 2011, Pfizer Inc., the manufacturer of Roxarsone, voluntarily suspended its manufacturing and distribution (FDA 2011).

The extensive use of arsenic in poultry production has resulted in contamination of the from 26 to 55 billion pounds of waste generated each year by the U.S. broiler chicken industry, 90% of which is added to fields and cropland as fertilizer. This arsenic has likely contaminated the communities where this poultry waste is generated or dispersed (IATP 2006).

In addition, marine and freshwater fish as well as shellfish can contain relatively high concentrations (up to 120 ppm) of arsenical compounds. However, these are naturally-occurring organic arsenic compounds that are considered muchless harmful than the inorganic form and not believed to pose a general public health threat(ATSDR 2007).

In certain rare instances, contaminated toys may be an exposure source for children. A 2009 study of children’s toys by HealthyStuff.org found arsenic in 9 out of 669 total products tested (1.3 percent), and found arsenic levels in certain products in excess of 1,000 ppm. As such, arsenic may not be as common in toys as are other heavy metals, such as lead and cadmium, but couldresult in exposure depending on the type of toy and the use by the child.

Childhood Exposure to Arsenic in Michigan

Children in Michigan are at particular risk ofarsenic exposure given the concentration of arsenic in the geology of the eastern part of the state (AAP 2003). In a 2005 study, the Environmental Working Group reportedthat more than 3.1 million people in 979 communities in Michigan were potentially exposed to elevated levels of arsenic through their drinking water (EWG 2005). The community found to be the most contaminated by the study had an average arsenic level of 47.7 ppb, nearly five times the current maximum contaminant level of 10 ppb set by the U.S. EPA in 2002 (EWG 2005, EPA 2007).

Figure 1:Michigan Arsenic Levels in Groundwater (DEQ WaterChem Database)

Note: 1 μg/l= 1 Part-per-billion (ppb)

Of the 926 water systems serving Michigan, EWG detected arsenic contaminations above health limits in 200 systems (EWG).

Neurotoxicity and Arsenic

Arsenic has been associated with neurotoxic effects in both animal studies and in epidemiologic studies in humans. In adults, arsenic has been shown to cause peripheral neuropathy, including electrical sensations, sensitivity, and weakness of the hands and feet (AAP 2003). Children, however, are more susceptible to arsenic, due to their smaller size, lower detoxification rate, and developing nervous system (AAP 2003). A meta-analysis of studies comparing children living in areas with higher levels of arsenic and lower to no levels of arsenic concluded that arsenic may be strongly associated with lower IQ in children;a study by Dong and Su (2008) found mean IQ to be up to six points lower in highly exposed children than in minimally exposed children. A study by Tsai et al. (2003) found significant associations between arsenic concentrations in home well water and increased attention switching and decreased pattern memory recognition in neurobehavioral studies of children. Even in preschool-aged children, exposure to arsenic in drinking water was associated with reductions in both performance and processing speed while conducting a standardized test of intelligence, although the highest arsenic levels in well water observed in this study were exceedingly high (>3000 ppb) (Wasserman, 2007). Additionally, several cross-sectional studies have established a link between arsenic exposure and neurobehavioral deficits in school children (Grandjean and Murata 2007).

Furthermore, exposure of mothers to arsenic during pregnancy may have detrimental effects on child development. Increased arsenic exposure in drinking water was also associated with decreases in learning and memory behavior and some reflex response in rats that were exposed both in utero (through their mother’s drinking water) and post-natally (Xi et al. 2009). Importantly, the study measured arsenic levels in the brain—demonstrating that the rats were exposed to arsenic through the placenta as well as through drinking water, an observation that has also been made in humans (Xi et al. 2009, AAP 2003). A wide range of neurotoxicological effects have been attributed to exposure to a variety of doses of inorganic arsenic. (Bundschuh et. al, 2009).

The most likely currently proposed pathway for the neurotoxic effects of inorganic arsenic exposure is as follows: ingested arsenic is primarily absorbed in the small intestine. Following this, the arsenic is methylated (changed from an inorganic to an organic form), afterwhich about 50% will be excreted in the urine after 3 to 5 days. A small portion of the ingested inorganic arsenic may also be excreted unchanged. In cases of chronic ingestion (this would include examples where home well water is heavily contaminated), arsenic will accumulate in the liver, kidneys, heart, lungs, muscles, gastrointestinal tract, spleen, and in the central nervous system, including the brain (Ratnaike 2003). These organic metabolites of arsenic, when in the brain, can change the cytoskeletal structure of neurons (Vahidniaet al. 2008), which can lead to behavioral changes, confusion, and memory loss, among other effects (Ratnaike 2003).

There is strong evidence for neurological harm as a result ofarsenic exposure, but there has been no well-established threshold dose of arsenic needed for these neurological effects to occur. (Grandjean and Murata, 2007). Dose-response relationships (higher exposures associated with worse health outcomes) have been noted. Currently, the best guideline as a maximum arsenic concentration for home drinking water is 10ppb, the EPA’s limit for public drinking water systems, although this limit is based not only on health considerations, but also the economic cost of treating drinking water (EPA 2008).

Policy Summary and Analysis

As described above, the major concerns regarding arsenic exposures to children are drinking water, contaminated soil, arsenic in pressure-treated lumber, and foods contaminated with arsenical pesticides and growth enhancers. There is evidence of an association between childhood exposure to arsenic and neurotoxicity. The evidence supports the need to take measures to reduce human exposures to arsenic to protect human health.

Some legislative and regulatory measures related to arsenic exist at the state level in Michigan and other states to protect human health and the environment. Herein, best policy practices from other states will be mentioned, and recommendations will be made to help protect children from exposure to arsenic in Michigan. In order to help reduce population exposures to arsenic in the United States, EPA limits the level of arsenic in drinking water to 10 parts per billion (ppb). EPA expects a population risk of 5 in 10,000 at this level of regulation (IRIS, 1998) The UN also recommends 10 ppb to best protect health (IARC, 2004). Because inorganic arsenic is a carcinogen there is no threshold value and even very small exposures are not considered safe (IRIS, 1998).

Drinking Water

Michigan Policy Highlights

1. For a fee MDNRE will either test, or assist individuals in testing their wells for arsenic levels (MDEQ, 2001)
2. Michigan has no other policy that met our specific criteria addressing arsenic in drinking water.

Analysis and Policy Highlights from Other States

1. Although federal standards are 10 ppb, a California bill signed in October 2007 by Governor Schwarzenegger contains a provision that requires bottled water companies to disclose the following statement, if applicable: "Arsenic levels above 5 ppb and up to 10 ppb are present in your drinking water. While your drinking water meets the current EPA standard for arsenic, it does contain low levels of arsenic. The standard balances the current understanding of arsenic's possible health effects against the costs of removing arsenic from drinking water. The State Department of Public Health continues to research the health effects of low levels of arsenic, which is a mineral known to cause cancer in humans at high concentrations and is linked to other health effects, including, but not limited to, skin damage and circulatory problems” (Cal Health &Saf Code § 111071).
2. California provides funding for small communities (less than 20,000 residents) to provide alternative sources of water or to treat water where arsenic levels exceed the maximum contaminant level of 10 ppb (Cal Pub Resources Code § 30950).
3. California provides funding for the improvement, replacement, or rehabilitation of domestic water systems contaminated with arsenic (Cal Wat Code § 13885).
4. California also provides funding for contaminant removal programs, which include the removal of arsenic (Cal Wat Code § 79545).
5. New Jersey allows for the state’s Department of Environmental Protection to take direct oversight of water supply remediation efforts if arsenic is detected in the given water supply (N.J. Stat. § 58:10C-27).
6. New Mexico allows for the use of Water Conservation Fund money for the testing of non-community water systems for arsenic (and other contaminants) and developing notification requirements (N.M. Stat. Ann. § 74-1-13.1).
7. North Carolina requires that, 30 days after the issue of a certificate of completion, a newly constructed private drinking well be tested by the local health department to ensure that the water from said well is in accordance with standards set by the Commission for Public Health. The standards shall include testing for arsenic (N.C. Gen. Stat. § 87-97).

Evaluation and Recommendations

• Michigan should require testing of private drinking wells after their installation to ensure that they do not contain arsenic-contaminated water (above 10 ppb).
• Michigan should establish a funding source for alternative water or water treatment in small communities, where arsenic is present at or above 10 ppb in public water systems.
• Michigan should identify a funding source for domestic water system improvement, replacement, and rehabilitation if arsenic is detected above 10 ppb.

Arsenic in Consumer Products

Michigan Policy Highlights

1. Michigan does not have any policy that meets our specific criteria regarding arsenic in consumer products.

Analysis and Policy Highlights from Other States

1. California prohibits the sale of toys with a coating that contains more than 0.1% soluble arsenic.
2. Maine passed a bill that confirms the restriction of the sale of arsenic-treated wood or wood products that are not permitted by the EPA (38 M.R.S. § 1682).
3. Maine sellers of residential property began providing purchasers with information about arsenic in private water supplies and arsenic in treated wood following statewide bans on the sale of lumber treated with arsenic. This followed provisions in the ban requiring that the Real Estate Commission provide the state with a description of its efforts to raise awareness of arsenic contamination in well water and in treated lumber among home buyers and sellers (L.D. 1309)
4. Maine has prohibited the disposal of arsenic-treated lumber products through any means aside from including it as municipal solid waste thatwill be sent to a lined landfill. As such, the burning, chipping or composting of arsenic treated lumber is prohibited (L.D. 1309).
5. Massachusetts prohibits the sale of any toy or confectionery wholly or partially coated in arsenic (ALM GL ch. 270, § 10).
6. Massachusetts also prohibits the sale or distribution of woven fibers and papers containing arsenic (ALM GL ch. 270, § 12).
7. New Hampshire prohibits the sale of woven fabric or paper or articles of clothing or household use containing, in part or in whole, such material, if the material is contaminated with arsenic (RSA 339:45).
8. North Carolina allows for the State Board to develop guidelines for sealing existing arsenic-treated wood in playground equipment or establishing a timeline for removing existing arsenic-treated wood on playgrounds and testing the soil on such playgrounds for contamination caused by the leaching of arsenic-treated wood (N.C. Gen. Stat. § 115C-12).

Evaluation and Recommendations

• Michigan should prohibit the sale of toys and children’s products that contain arsenicabove 40ppm.
• Michigan should require that property sellersnotify purchasers if arsenic in private water supplies on the properties to be purchased has been detected at levels above 5 ppb.
• Michigan should require that property sellers notify purchasers if wood products on the property contain CCA.
• Michigan should prohibit the sale of woven fibers (cotton, etc.) and papers that contain arsenic.
• Michigan should develop guidelines to seal existing playground equipment so that children do not have access to CCA in pressure-treated wood or require equipment to be removed.
• Michigan should require that CCA-treated wood in public playgrounds be treated every year with a sealant in order to minimize the amount of dislodgeable arsenic on the surface of the wood.
• Michigan should prohibit the sale of all arsenic-treated wood.

Summary of Policy Recommendations for Arsenic in Michigan

• Michigan should test private drinking wells after their installation to ensure that they are not yielding arsenic-tainted water, as is done in North Carolina.
• Michigan should take control of the rehabilitation of water supplies that have arsenic levels above the EPA maximum contaminant level of 10 ppb, as is done in New Jersey.
• Michigan should provide funding for alternative waters sources or water treatment in small communities whose water supply is contaminated with arsenic, as is done in California.
• Michigan should locate a funding sourcefor domestic water system improvement, replacement, or rehabilitation if arsenic is detected at or above 10 ppb.
• Michigan should prohibit the sale of toys and children’s products that contain arsenic, as is done in California and Massachusetts.
• Michigan should require that realtors inform purchasers about arsenic in ground water and wood products, as is done in Maine.
• Michigan should prohibit the sale of woven materials that contain arsenic, like Massachusetts and New Hampshire.
• Michigan should develop guidelines to seal existing CCA-treated pressure-treated wood playground equipment annually to prevent children from coming in contact with CCA, as is done in North Carolina.
• The Michigan legislature should call upon the FDA to move toward regulating the amount of inorganic arsenic that can be present in food. Specifically the FDA should set limits that reflect a cumulative approach to dietary arsenic exposures, as opposed to evaluating each exposure source separately.

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