The Role of ICP-MS in Understanding the Toxicological Link Between Lead Contamination in Cannabis and Hemp Products and Human Disease – Part 1

Lead represents the most serious toxicological threat of all the heavy metal contaminants on the growing of cannabis and hemp. There is no question that our historical dependence on using materials made from lead, including car batteries, paint pigments, gasoline, plumbing, ammunition, cable sheathing, lead crystal glass, radiation protection and solders has contributed to this problem. Decades of using these lead-based products are still having an impact on our soil and aquatic ecosystems and thus having a negative effect on the growing of cannabis and hemp. As result, lead is getting the most scrutiny by state regulators, not only because of its historical importance as a human toxicant, but also because elevated levels of lead are being reported by researchers in many cannabis consumer products.

This two-part article will therefore focus on the important role of inductively coupled plasma-mass-spectrometry (ICP-MS) in being able to meet lower regulatory demands to better understand the link between lead toxicity and human disease.

The majority of the thirty-six states in the US where medicinal and recreational cannabis is legal regulate four heavy metals lead (Pb), arsenic (As), cadmium (Cd), mercury (Hg), commonly known as the big four. However, some states include other elements such as chromium (Cr), selenium (Se), barium (Ba), silver (Ag), copper (Cu), antimony (Sb), and zinc (Zn). Moreover, there is compelling evidence in the public domain, there are an additional five elements, cobalt (Co), nickel (Ni), vanadium (V), manganese (Mn), and uranium (U) found in natural ecosystems (soil, rocks, water, air) and from industrial anthropogenic activities that could be sources of contaminants that could potentially be accumulated by the plant.

So, with federal oversight around the corner, it is only a matter of time before the industry will be required to expand the list of regulated elements beyond the big four. But what should an expanded list look like? We can look to the pharmaceutical industry for guidance, which regulates up to twenty-four elemental impurities in drug products, by setting toxicology-driven permitted daily exposure limits (PDE) of the four major drug delivery methods (oral, intravenous, inhalation, transdermal), based on comprehensive risk assessment studies (1). However, we have no way of knowing in what quantities people consume cannabis or cannabinoid consumer products. For that reason, it is very difficult to fully understand the impact of elemental contaminants on consumer safety when there have been no risk analysis studies carried out and, as a result, no suggested maximum daily dosage on which to base the toxicity calculations.

Human health

Understanding the effects of trace metals on human health is as complex as it is fascinating. We know that too low or too high a concentration of essential trace elements in our diet can affect our quality of life. On the other hand, metallic contamination of the air, soil and water supplies can have a dramatic impact on our well-being. There are many examples that highlight both the negative and positive effects of trace metals on our lives. For instance, the effect of lead toxicity is well documented, as was demonstrated by the negligence of public health officials in Flint, Michigan, who did not adequately treat the drinking water supply when it changed from Lake Huron to the Flint River and as a result contaminated the water supply with abnormally high levels of lead. The movie Erin Brokovich alarmed us all to the dangers of hexavalent chromium (Cr VI) in drinking water, but how many of the audience realized that trivalent chromium (CRIII) metal is necessary for the metabolism of carbohydrates and fats? A few years ago, Dr Oz, the infamous TV doctor in the US, alarmed his viewers about high levels arsenic in apple juice, but what he failed to say was that it was not the highly toxic inorganic form of arsenic, but the arsenic that had been metabolized by the apple tree to the less toxic organic form. Selenium, which is found in many vegetables including garlic and onions, has important antioxidant properties, but do we know why some selenium compounds are essential, while others are toxic? Clearly, they are all complex questions to be answered to fully understand the roll of trace metals in the mechanisms of human diseases.

Heavy metals in cannabis and hemp

Cannabis and hemp are known to be hyper-accumulators of contaminants in the soil. That is why they have been used to clean up toxic waste sites where other kinds of remediation attempts have failed. In the aftermath of the Chernobyl nuclear melt down in the Ukraine in 1986, industrial hemp was planted to clean up the radioactive isotopes and heavy metals that had leaked into the soil and ground waters (2). Of course, Chernobyl is an extreme example of contamination, but as a result of normal human industrial activities over the past few decades including mining, smelting, electroplating, gasoline production, energy production, use of fertilizers, pesticides, waste treatment plants, paint and plumbing materials etc., heavy metal pollution has become one of the most serious environmental problems today. As a result, considerations about where cannabis and hemp are grown, is going to be critically important because it could have serious implications on the level of heavy metals that are being absorbed by the plant and, as a result, the purity of cannabinoid consumer products that are used as therapeutics for patients with compromised immune.

There are currently four heavy metals known as the big four (Pb, As, Cd, Hg), which are required by the thirty-six states where medicinal and recreational cannabis is legal in the US. However, based on compelling evidence in the public domain, there are an additional ten elemental contaminants found in natural ecosystems (soil, rocks, water, air) and from industrial anthropogenic activities that could be potential sources of contaminants accumulated by the plant. It is only a matter of time before federal oversight will arrive and require the industry to expand this list of regulated elements beyond the big four. However, in the meantime, lead is getting the most attention by state regulators, not only because of its historical importance as a human toxicant, but also that elevated levels of lead have recently been found in many cannabis consumer products, as reported in a recent ASTM workshop (3).

Sources of lead

So, if lead represents the most serious ecological threat of all the heavy metal contaminants on the growing of cannabis and hemp, what are the most common environmental sources? There is no question that our historical dependence on using materials made from lead, including car batteries, paint pigments, gasoline, plumbing, ammunition, cable sheathing, lead crystal glass, radiation protection and solders has contributed to this problem. Decades of using these lead-based products are still having an impact on our soil and aquatic ecosystems and thus having a negative effect on the growing of cannabis and hemp. Some of these sources include:

• The long-term weathering of galena rocks (lead sulfide), the most common of the lead-based ores will produce a lead-rich soil in the surrounding areas.
• Lead smelting plants and refineries generate copious amounts of lead dust and particulates, which gets into the environment and the soil.
• Automobile emission residues particularly from tetra ethyl lead used in the production of leaded gasoline before it was banned in 1996, is one of the major reasons for extremely high levels of lead in soil, particularly around major highways.
• Approximately 50 years of using lead-based paint before it was banned in 1978, particularly in older buildings has contributed to high levels of lead in household dust and particulates.
• The use of leaded water pipes has also contributed to higher lead levels in the municipal drinking water supplies if it is not chemically treated to reduce corrosion, as demonstrated by the Flint, MI, drinking water crisis in 2014.
• Many fertilizers and nutrients used to grow cannabis and hemp are sourced from phosphate rocks, which are notorious for containing high levels of lead and other heavy metals.
• Many electronic cannabis delivery vaping systems have components made from brass, which often contains lead to make it easier to machine. In addition, battery terminal wires are also connected using lead-based solder.

To fully understand why lead is the most serious of the classic big four heavy metals, especially when it comes to the cultivation of cannabis and hemp, let us take a closer look at its toxicity impact on human health, particularly for children and young adults.

Lead toxicity

Lead has no known biological or physiological purpose in the human body, but is avidly absorbed into the system by ingestion, inhalation and to a lesser extent by skin absorption (4). Inorganic lead in submicron size particles in particular can be almost completely absorbed through the respiratory tract, whereas larger particles may be swallowed. The extent and rate of absorption of lead through the gastrointestinal tract depend on characteristics of the individual and on the nature of the medium ingested. It has been shown that children can absorb 40–50 percent of an oral dose of water-soluble lead compared to only 3–10 percent for adults (5). Young children are particularly susceptible, because of their playing and eating habits and typically have more hand-to-mouth activity than adults (6). Lead is absorbed more easily if there is a calcium/iron deficiency, or if the child has a high fat, inadequate mineral and/or low protein diet. When absorbed, lead is distributed within the body in three main areas – bones, blood, and soft tissue. About 90 percent is distributed in the bones, while the majority of the rest gets absorbed into the bloodstream where it gets taken up by porphyrin molecules (complex nitrogen-containing organic compounds providing the foundation structure for hemoglobin) in the red blood cells (7). It is therefore clear that the repercussions and health risks are potentially enormous, if humans (especially young children) have a long-term exposure to high levels of lead.

Health effects

Lead poisoning affects virtually every system in the body, and often occurs with no distinctive symptoms. It can damage the central nervous system, kidneys, and reproductive system and, at higher levels, can cause coma, convulsions, and even death. Even low levels of lead are harmful and are associated with lower intelligence, reduced brain development, decreased growth and impaired hearing (8). The level of lead in someone’s system is confirmed by a blood-lead test, which by today’s standards is considered elevated if it is in excess of 5 µg/dL (microgram per deciliter or 50 parts per billion) (9). However, the long-term effects of lead poisoning have not always been well- understood. In the early-mid 1960s, remedial action would be taken if a blood lead level (BLL) (or threshold level as it was known then) was in excess of 60 µg/dL. As investigators discovered more sensitive detection systems and designed better studies, the generally recognized level for lead toxicity has progressively shifted downward. In 1970 it was lowered to 40 µg/dL and by 1978 the level had been reduced to 30 µg/dL. In 1985 the CDC published a threshold level of 25 µg/dL, which they eventually lowered to10 µg/dL in 1991. It stayed at this level until it was reduced to 5 µg/dL in 2012. However, as our understanding of disease improves and measurement technology gets more refined, this level could be pushed even lower in the future (10). Figure 1 shows the trend in blood lead levels considered elevated by the Centers for Disease Control (CDC), since the mid-1960s.

Figure 1: The trend in blood lead levels (µg/dL) in children considered elevated by the Centers for Disease Control and Prevention (CDC), since the mid-1960s.

Currently the major source of lead poisoning among children comes from lead-based household paints, which were used up until they were banned in 1978 by the Consumer Product Safety Commission. Prior to this, leaded gasoline was the largest pollutant before it was completely removed from the pumps in 1995. Other potential sources include lead pipes used in drinking water systems, airborne lead from smelters, clay pots, pottery glazes, lead batteries and household dust. However, awareness of the problem combined with preventative care and regular monitoring, have reduced the percentage of children aged 1–5 years with elevated blood levels (≥5 μg/dL) in the US from 26 percent in the early-mid 1990s to less than 2 percent in 2014. These data were taken from a recent National Health and Nutrition Examination Survey (NHANES) report (11). However, it is important to emphasize that there is now an FDA-approved prescription cannabis-derived cannabidiol (CBD) drug on the market (Epidiolex) for the treatment of seizures associated with two rare and severe forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome, in patients two years of age and older. It is therefore critically important that these drugs are derived from cannabis plants that are free of any heavy metal contamination.

Don’t miss part two

Be sure to catch the second part of the article, which looks at the role of ICP-MS compared to other atomic spectroscopy (AS) techniques and how the former’s development, performance improvements, and unique capabilities have been a major factor in reducing detection levels to improve the sector’s understanding of lead toxicity and its impact on human health. This is of particular importance for regulating lead in cannabis consumer products because if state-based maximum limits are reduced even lower when federal regulators begin to scrutinize the industry, modern ICP-MS instrumentation will be able to meet the demand to ensure consumer safety.

Further reading

1. Elemental Impurities in Pharmaceuticals: Updates: United States Pharmacopeai (USP) Website: http://www.usp.org/chemical-medicines/elemental-impurities-updates
2. From Laboratory Experiments to Large Scale Application –  An  Example  of  the  Phytoremediation  of  Radionuclides,  P.  Soudek et.al.  Advanced  Science  and Technology for Biological Decontamination of Sites  Affected  by  Chemical  and  Radiological  Nuclear  Agents, pp 139-158, 2 007, https://www.researchgate.net/publication/226765625_FROM_LABORATORY_EXPERIMENTS_TO_LARGE_SCALE_APPLICATION__AN_EXAMPLE_OF_THE_PHYTOREMEDIATION_OF_RADIONUCLIDES
3. A Recap of ASTM’s Workshop on Measuring Elemental Contaminants in Cannabis and Hemp Consumer Products, Robert Thomas, Analytical Cannabis, August 5, 2021, https://www.analyticalcannabis.com/articles/a-recap-of-astms-workshop-on-measuring-elemental-contaminants-in-cannabis-and-hemp-consumer-313229
4. J. Savory and M. R. Willis, Clinical Chemistry, 40, 1387 (1994)
5. Agency for Toxic Substances and Disease Registry (ATSDR), Toxicological Profile for Lead, Section 3.3: Toxicokinetics, August, 2007, (https://www.atsdr.cdc.gov/toxprofiles/TP.asp?id=96&tid=22).
6. Preventing Lead Poisoning in Young Children, Chapter 2: Absorption of Lead, Centers for Disease Control and Prevention (CDC), 1991, https://www.cdc.gov/nceh/lead/publications/books/plpyc/contents.htm
7. H. L. Needham, Case Studies in Environmental Medicine-Lead Toxicity, U. S. Dpt. of Health and Human Services (1990)
8. Preventing Lead Poisoning in Young Children, Lead Information Page, Centers for Disease Control and Prevention (CDC), https://www.cdc.gov/nceh/lead/default.htm
9. Childhood Blood Lead Levels in Children Aged <5 Years: United States, 2009–2014, Morbidity and Mortality Weekly Report (MMWR), Surveillance Summaries / January 20, 2017 / 66 (3);1–10, https://www.cdc.gov/mmwr/volumes/66/ss/ss6603a1.htm
10. CDC Response to Advisory Committee on Childhood Lead Poisoning Prevention Recommendations in “Low Level Lead Exposure Harms Children: A Renewed Call of Primary Prevention” (2012) , https://www.cdc.gov/nceh/lead/ACCLPP/blood_lead_levels.htm
11. Record of Proceedings from the Meeting of the Lead Poisoning Prevention Subcommittee of the NCEH/ATSDR Board of Scientific Counselors, Centers for Disease Control and Prevention (CDC), Atlanta, GA, September 19, 2016