**3. Legalization and the national and international permissible levels for these heavy metals**

In recent years the legalization of producing marijuana (cannabis and cannabisderived products) especially in certain specific states within the United States has caused a level of alarm in part because of the presence of heavy metals within these products. As the result of the expansion in the commercialization of these products, has created the challenge to now measure heavy metals in cannabis and cannabisinfused commodities. Marijuana is now legal and approved for both medical and recreational use in 33 states within the United States and the District of Columbia (Washington, DC) [132]. However, the raw materials (cannabis and hemp plants) are known to be hyperaccumulators of contaminants such as heavy metals that may be present in the medium used to cultivate the plants, whether it is the soil, the fertilizers used, and in any other growth promoting substances used to supply needed nutrients. With that said, the alarm has been sounded to critically monitor the levels of heavy metal contaminants present in any part of the growing process to ensure that the marijuana-cannabis material and its food-associated products are safe to consume [133].One of the major remaining issues, at least in the United States, is the lack of federal government oversight regarding measuring contaminants in marijuana (cannabis and cannabis-prepared food products) produced in the United States. The U.S. federal government has removed itself from this oversight and in doing so they have delegated regulatory issues to the individual states to regulate the use of marijuana cannabis and cannabis-prepared products. This adds a financial burden to states that are often financially stressed to meet these demands.

What individual states have emphasized has been to focus on the manufacturers of these marijuana (cannabis and cannabis-prepared food products) to show

#### *Role of Heavy Metals in the Incidence of Human Cancers DOI: http://dx.doi.org/10.5772/intechopen.98259*

regulation by measuring for the following four major heavy metals: lead (Pb), arsenic (As), cadmium (Cd), and mercury (Hg). The levels of metals must be below maximum limits, based mainly on regulations set by the pharmaceutical industry in USP Chapter 232 and ICH Q3D guidelines [134, 135]. The state of California is usually the state that places severe restrictions on levels allowed. This policy is considered to be the gold standard in regulating cannabis and hemp. It determines the levels allowable in both the oral (edibles) and inhaled (vapes) cannabis products to be to safe to consume only if these four heavy metals are present at levels below those shown in **Tables 1** and **2**, based on typical consumption of 10 g/day of cannabis material [137].

For analytical measurements of heavy metal contaminants, the state of California requires that at least half a gram of sample must be used for testing purposes. The analytical testing methodology recommends that inductively coupled plasma mass spectrometry (ICP-MS) serve as the method of choice [136]. ICP-MS is a sophisticated multi-element analytical technique, capable of measuring levels to parts per trillion (ppt) using mass spectrometry to identify and measure positively charged ions. The testing methods occur in an extremely energetic argon plasma at approximately 6,000-7,000°C [138]. However, this method requires a solution technique, meaning any solid samples must be dissolved/digested before being analyzed. Most cannabis-related samples are solid materials, powders, concentrates and extracts, which invites several challenges. In addition, cannabinoid oils, which are mainly hydrophobic (not miscible with water), must also be digested prior to analysis.

As mentioned previously in the United States within the federal government exists the Environmental Protection Agency (EPA). The function of the EPA is to set federal standards for a variety of compounds and substances in terms of determining their presence in the environment, which includes the air, soil, ground water, lakes, and rivers. Over the past several years, based upon political influences, the minimum acceptable levels for a variety of substances such as heavy metals have been increased for no other reason than to reduced regulations without factoring the environmental impact. These changes come at the expense of potentially reducing the overall quality of air, soil, ground water, lakes and rivers, thus imposing potential harm to people (children and adults). As mentioned earlier in the discussion of sources of lead contamination, recent incidence of dramatically higher levels of lead present in the drinking water of those living in the Flint, Michigan area is an example of political incompetence when the politicians in the community changed the source of the community drinking water from Lake Michigan to the Detroit River, which was highly contaminated because of age of the lead pipes used to pump the water from the river. The rationale for the change was to reduce the overall costs of providing usable water for the community. Based upon the excessive negligence involved in this case, compensation costs to the citizens of the community has been in the hundreds of millions of dollars not to mention the total costs involved to completely remove and install a new water delivery system devoid of metal pipes of


**Table 1.**

*Heavy metal limits (cannabis & cannabis-hemp) by state of California [136].*


#### **Table 2.**

*Heavy metal limits according to the World Health Organization (https://www.who.int/ceh/capacity/ heavy\_metals.pdf?ua=1).*

any kind. The long-term consequence of this unfortunate and unnecessary change on the overall sustained health of the community is yet to be determined.

In Europe the European Environment Agency (EEA), controls the level of pollutants such as heavy metals [139]. Regarding heavy metal emissions, across the 33 European countries the following is a short summary of recent achievements in the EU with respect to reducing heavy metals concentrations: (a) Since 1990 across all 33 countries, lead admissions decreased by 93%, mercury by 72%, and cadmium by 64%; (b) Reductions in levels of lead have occurred by 2004 due in part to the removal lead from gasoline; (c) Reductions in levels of mercury have occurred as the result of changes in energy use both in industries and other processes used in industry; and (d) Reductions in levels of cadmium are attributed to operational changes in industries across the board.

A remaining issue in a select set of areas of Europe is the continued presence of unacceptable levels of arsenic, cadmium, lead, mercury and nickel as the result of the presence of these substances still in the atmosphere [140]. The collective set of excessive metal excesses due cause local health issues, in part, because of the presence of localized industrial plants that release emissions of the pollutants. With that said, even though the emissions are concentrated in localized areas, this does not limit nor restrict the impact on health concerns because the pollutants are able to enter the food chain through ground soil and water contamination. Across the EU member countries there is the political will to do what is necessary and needed to sustain the momentum to continue to reduce pollutants in the environment.

#### **4. Mitigation of the negative effects of these heavy metal materials**

One could deduce that the presence of heavy metals in the environment combined with occupational exposure is a problem for human health. A pertinent question to ask then is "what can be done to reduce human heavy metal exposure?" Several remedies or actions can be considered that have been shown to be effective, they are:


be harvested at regular intervals, dried and disposed of as contaminated solid waste or used to recover valuable heavy metals. It is the feasibility and future optimization of this approach using marine macroalgae that forms the basis of the proposed studies. Bioavailability of heavy metals is highly dependent upon several environmental factors. Biomonitors utilizing plants growing under "natural" conditions where biotic and abiotic factors are intercalated reduces the need for making assumptions regarding bioavailability of metals. Plants themselves can alter the microenvironment around them, thus altering the amount of metals that are biologically available. Bulk water analysis may not measure the conditions at the membrane level where changes occur. Benthic plants can provide valuable information regarding past environmental conditions over weeks and months. This is particularly important in plants growing within the intertidal zones where the metal content of water may fluctuate continuously [142].


friendly, and esthetically pleasing. According to studies conducted, based on the natural ability of extraction, approximately 500 plants and other organisms have been identified as hyperaccumulators of one or more the heavy metals. In addition, further research integrating biotechnological approaches with comprehensive multidisciplinary research is needed to improve plant tolerance and reduce the accumulation of toxic metals in soils [144].

e.Other. As stated, heavy metals endanger overall human health. Of importance are the conditions especially when as the result of testing identifies heavy metal levels to be significantly above required standards for each. What still remains as an important factor regarding overall human health is that sustained elevated levels of heavy metals are indeed carcinogenic. The majority of studies performed designed to determine the pathway of heavy metal exposure that results in the carcinogenic effect of heavy metals in human exposure takes place via heavy metal contamination the overall food chain thereby impacting the quality agriculture, specifically the generation of agricultural products such as food and food by-products. In addition to the exposures that account for heavy metal contamination, there are additional factors that account for human exposure. This additional exposure can occur through the use of pesticides directly contaminating soil and also through waste-water run-off contamination. There are natural remediation methods that can help remediate areas of heavy metal contamination such as the presence of geological specific rock formations. With that said, it is still necessary to employ methods that address the heavy metal remediation especially when the sites of contamination are present in food products - fruits and vegetables. In addition, remediation of soil areas and water may also must be considered because these factors also contribute to heavy metal food contamination. Thus, it is imperative heavy metal remediation methods be used constructively in order to maintain overall public health [145].
