Why are heavy metals toxic? Lead and Carbon are in the same group. One is toxic, the other is not

Question

I have read the different answers on the toxicity of heavy metals but I am still confused about the topic. Why does the mass of the nuclei matter when chemical reactions only involve the electrons. Carbon and lead are in the same chemical group and thus have the same chemical properties.

Answer 1

You're right to say that chemical reactions primarily involve the valence electrons of an atom. However, there are other factors that are key to understanding the difference in toxicity between lead and carbon. Mass isn’t really the explanation — correlation isn’t causation. Li and Be may be toxic in certain scenarios.

1. Some heavy metals share chemical similarities with essential elements our body uses. Lead, for example, can mimic calcium and sneak into important biological processes (e.g., disrupting neurotransmitter release by activating protein kinases).
2. Oxidative Stress: Some heavy metals can generate free radicals or reactive oxygen species, due to their flexible oxidation states and redox potential, which damage cells. (https://www.intechopen.com/chapters/71913)
3. Heavy metals tend to bioaccumulate and remain in organisms over time, specifically in the kidneys and liver. Because lead has no known biological role, there are no efficient excretion pathways for it. Carbon is continuously cycled through metabolic processes.

Now, carbon's small atomic size and stable quadrivalent electron configuration allow it to form strong bonds with itself and other elements, creating the vast diversity of organic molecules crucial for life (like DNA, proteins, and carbohydrates). The inability to easily lose electrons prevents it from exhibiting these toxic behaviors in biological systems. Its chemistry is perfectly tailored for the organic molecular backbone.

***It's important to note that not all heavy metals are inherently toxic. Some, like iron and copper, are essential for our body in small amounts.

Good review article to read: https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.643972/full

Answer 2

It's not the "heavy" that makes a metal toxic. Lithium and Beryllium are considerably lighter but still toxic to humans. If the metals interact negatively within the human body, it is considered toxic. For e.g. Lead disrupts the functions of the digestive system, nervous system, respiratory system, reproductive system. In addition, it prevents enzymes from performing their normal activities. Lead even disrupts the normal DNA transcription process and causes disability in bones. Lead as such has no physiological role in the body and even smaller levels of lead can cause toxicity.

You can refer to below studies for more information:

1. Mahdi Balali-Mood,Kobra Naseri, Zoya Tahergorabi, Mohammad Reza Khazdair, Mahmood Sadeghi, Toxic Mechanisms of Five Heavy Metals: Mercury, Lead, Chromium, Cadmium, and Arsenic, . Pharmacol., 2021 DOI: 10.3389/fphar.2021.643972
2. Jaishankar M, Tseten T, Anbalagan N, Mathew BB, Beeregowda KN. Toxicity, mechanism and health effects of some heavy metals. Interdiscip Toxicol. 2014; 7(2):60-72. doi: 10.2478/intox-2014-0009
3. Tchounwou PB, Yedjou CG, Patlolla AK, Sutton DJ. Heavy metal toxicity and the environment. Exp Suppl. 2012;101:133-64. doi: 10.1007/978-3-7643-8340-4_6

---

I should add more on what "actually" makes lead toxic to humans. Please see this simplified diagram:

(Image source)

I'll go by each routes:

• Route 1: Lead is known to have a strong affinity towards sulfur. In human body, sulfur exists in the form of thiols. So, lead tries to bind with thiol group¹ leading to major implications.

• Route 2: Lead is able to produce free radical and reactive oxygen species (ROS) via Fenton-Haver-Weiss pathway² possible by stimulating NADPH oxidases or by competing for the metal binding site of an enzyme/protein (Route 3) or by attacking the thiols moiety of protein (Route 1). The mechanism is below:

  It causes a destructive behavior known as oxidative stress. One of the major implication of oxidative stress is lead-induced hypertension and cardiovascular diseases³

• Route 3: Lead is known to mimic calcium because they share similar properties (In its +2 cationic form, lead has a radius of 132 pm while the calcium cation has a radius of 106 pm. In their elemental forms, lead has a radius of 175 pm and calcium has a radius of 197 pm). And that is the reason, lead compete with calcium and substitutes calcium from cells, tissues and enzymatic sites. One of the major effect is on calmodulin which is a calcium binding protein and lead will try to replace calcium inhibiting phosphorylation of brain membranes⁴.

There are other diagrams which which shows the mechanistical and pathological effect of lead in human body like this and this (the latter one shows the effect in DNA, RNA and lipids)

References:

1. Magyar JS, Weng TC, Stern CM, Dye DF, Rous BW, Payne JC, Bridgewater BM, Mijovilovich A, Parkin G, Zaleski JM, Penner-Hahn JE, Godwin HA. Reexamination of lead(II) coordination preferences in sulfur-rich sites: implications for a critical mechanism of lead poisoning. J Am Chem Soc. 2005 127(26):9495-505. doi: 10.1021/ja0424530
2. Kehrer JP. The Haber-Weiss reaction and mechanisms of toxicity. Toxicology. 2000 Aug 14;149(1):43-50. doi: 10.1016/s0300-483x(00)00231-6
3. Mechanisms of lead-induced hypertension and cardiovascular disease, Nosratola D. Vaziri, American Journal of Physiology-Heart and Circulatory Physiology 2008 295:2, H454-H465, DOI: 10.1152/ajpheart.00158.2008
4. Habermann E, Crowell K, Janicki P. Lead and other metals can substitute for Ca2+ in calmodulin. Arch Toxicol. 1983 Sep;54(1):61-70. doi: 10.1007/BF00277816
5. https://sites.tufts.edu/leadpoisoning/pathways/lead-and-calcium/
6. FHW pathway mechanism image source: Trace Metals in the Environment by Daisy Joseph, 2023

Answer 3

I would answer this question in a different way. As others have pointed out above, elements behave differently than one another even when they have the same number of valence electrons. This makes it possible for some elements to be more toxic than others, even when they're in the same row of the periodic table. But (again, as others have pointed out) it doesn't explain why there's a tendency for the heavier elements to be more toxic. And then there's the curious fact that not all of the heavier elements are toxic, and not all of the lighter ones are non-toxic. On top of that, the mechanisms of toxicity are very different for different toxic elements.

I would argue that the general rule is this: organisms haven't evolved to deal with unusually high concentrations of elements. Heavy elements, because they're rare, are hardly ever encountered at high concentrations. Does this mean that they are necessarily toxic? No - organisms might be able to deal with high concentrations of them, just by chance. For this reason, some rare elements happen to be non-toxic. But others mess with biomolecular functions in ways that organisms haven't evolved to counteract.

In contrast, organisms must be able to deal with common elements at significant concentrations - in other words, those elements must be non-toxic, even if they're chemically reactive. For example, oxygen isn't toxic even in high concentrations because most organisms that couldn't tolerate oxygen went extinct eons ago, when the oxygen concentration in the atmosphere first rose to significant levels.

Hypotheses like this run the risk of being circular or meaningless. ("X isn't harmful to organisms because they've evolved to be resistant to X. The proof is that X doesn't harm organisms!") However, we can put this hypothesis to the test, at least to some degree, by looking at organisms that encounter different elements. Organisms should show specific adaptations to deal with reactive chemicals that are common in their particular environment; they should lack adaptations specific to dealing with rare chemicals. For instance, aerobic bacteria should generate antioxidants, and the genes coding for these defenses should show signs of conservative selection; this shouldn't be the case for anaerobic microbes that rarely encounter oxygen.

I apologize for not supplying more specifics (or citations). I'm in a bit of a rush. But I hope this way of re-framing the question is useful!

Answer 4

I apologize for not being very scientific in this, I will explain how I understand this, based on my experience as a chemist, my whole life trying to understand how these groupings of atoms behave. Chemistry is the science of how electrons fit together. I could say "the orbitals" of electrons, but we all know that there are no balls orbiting in atoms. Electrons are this phenomenon that occupies space in what we call an orbital. Sometimes orbitals are unstable and electrons are accommodated in other ways between nuclei.

Well then. From the moment the number of electrons reaches that of Gold, a very strange thing appears. The orbitals no longer behave according to the Schrodinger equation. In heavy atoms like gold, relativistic effects become significant because the inner electrons move at speeds close to the speed of light. This increases their relativistic mass and contracts the s orbitals while expanding the d orbitals. The unique color of gold is due to these relativistic effects. The contraction of the 6s orbital and expansion of the 5d orbital reduce the energy gap between these orbitals. This shifts the absorption of light to the blue end of the spectrum, making the reflected light appear yellow to human eyes. Relativistic effects also influence gold’s chemical behavior, making it more inert compared to other metals like silver. This is because the contracted 6s electrons are less available for bonding, contributing to gold’s resistance to oxidation and its ability to form unique compounds.

intuitively (it's all we chemists can do to understand these quantum phenomena), this causes a bubble. Extremely stable, causing a gold that does not react with almost anything. This little ball is the nucleus of everything that comes after in the periodic table.

But biochemistry (for me, at least and we are a product of biochemistry for me) is a way for atoms to organize themselves so that electrons can create gradients of thermodynamic properties suitable for creating the minimum entropy outputs we call life. Now, these little balls get in the way, they don't enter the game. They become insensitive to the entropic flows that cause life. This, my colleague, is how I understand that these heavy metals cannot be eliminated from the body. Biochemistry based on non-equilibrium thermodynamics has no way of dealing with them. The toxicity of metalloids, on the other hand, appears to have other factors. Biochemistry is a game between complex structures of non-metallic atoms with occasional and specific roles of metals, as in hemoglobin and chlorophyll. Precisely because of the distinct roles that metals are said to be "chelated" when assimilated into biochemical structures. The periodic table, however, includes a few intermediate elements between metals and non-metals, these metalloids. When they have lower atomic numbers, they have eccentric effects in biochemistry, a widely used property of B, Si, and Se. They may offer an exquisite effect on the molecule, but of course, it's use is limited. Although there is so much Si on Earth, life can't use more than a little quantity. In contrast, As, Sb, Te, and Ge are highly toxic and exposure can cause various physiological dysfunctions, growth defects, and human diseases. The toxicity of metalloids, on the other hand, appears to have other factors. Biochemistry is a game between complex structures of non-metallic atoms with occasional and specific roles of metals, as in hemoglobin and chlorophyll. Precisely because of the distinct roles that metals are said to be "chelated" when assimilated into biochemical structures.

Despite being heavier than Si, all four of these metalloids are lighter than gold, so this toxicity comes from other properties. In fact, the biochemistry of the toxicity has been an object of research (Front. Cell Dev. Biol., 28 August 2018, Sec. Cellular Biochemistry, Volume 6 - 2018 | https://doi.org/10.3389/fcell.2018.00099).

We have to take into account that life developed in the crust of a planet that contains much more phosphorus (1,050 mg/kg or 0.105%) than arsenic (1.8 mg/kg or 0.00018%) and much more selenium (0.05 mg/kg or 50 parts per billion, ppb)​ than (tellurium 0.001 mg/kg or 1 part per billion, ppb)​ and these two pairs of elements have very similar properties.

Phosphorus (P) and arsenic (As) are both group 15 elements in the periodic table, sharing many chemical properties due to their similar electronic configurations. Here are some key comparisons:

Chemical Properties (P/Ar) Oxidation States: Both elements exhibit common oxidation states of -3, +3, and +5. Hydrides: Both form hydrides, such as phosphine (PH₃) and arsine (AsH₃). These are similar in structure but differ in stability and reactivity; arsine is generally more toxic and less stable. Oxoacids: Phosphorus forms several oxoacids like phosphoric acid (H₃PO₄), while arsenic forms analogous compounds like arsenic acid (H₃AsO₄). These compounds have similar structures but differ in toxicity and some chemical properties. Similar Molecules Phosphates and Arsenates: Both elements form compounds such as phosphates (PO₄³⁻) and arsenates (AsO₄³⁻). These ions are structurally similar and often substitute for each other in minerals. Organic Compounds: Phosphorus and arsenic both form organophosphorus and organoarsenic compounds. These compounds are used in pesticides, herbicides, and other chemicals. However, organoarsenic compounds are often more toxic.

Selenium (Se) and tellurium (Te) are both chalcogens (group 16 elements) and share many similar chemical properties, but they also have distinct differences due to their positions in the periodic table.

Chemical Properties (Se/Te) Oxidation States: Both elements commonly exhibit oxidation states of -2, +4, and +6. Hydrides: Selenium forms hydrogen selenide (H₂Se), and tellurium forms hydrogen telluride (H₂Te). These hydrides are analogous in structure but differ significantly in stability and toxicity, with H₂Te being more unstable and toxic. Oxoacids: Selenium forms selenous acid (H₂SeO₃) and selenic acid (H₂SeO₄), while tellurium forms tellurous acid (H₂TeO₃) and telluric acid (H₂TeO₄). These oxoacids are structurally similar but have different chemical behaviors and reactivities. Allotropes: Selenium has several allotropes, including red, gray, and black forms, with different properties. Tellurium has fewer allotropes, mainly existing in a metallic form. Similar Molecules Compounds with Oxygen: Both form dioxides (SeO₂ and TeO₂) and trioxides (SeO₃ and TeO₃). These compounds are used in various chemical processes and have similar structures. Organometallic Compounds: Selenium and tellurium form organometallic compounds used in organic synthesis and materials science.

The fact that arsenic is confused with phosphorus is a true tragedy, as phosphorus is crucial in the most fundamental of biochemical reactions, the storage and release of energy. Arsenic spreads throughout the body and ends up being treated not as a foreign element, but as an essential part of metabolism.

(see, for instance, Environ Toxicol Pharmacol. 2015 Mar;39(2):668-76. doi: 10.1016/j.etap.2015.01.012. Epub 2015 Feb 3. The arsenic accumulation and its effect on oxidative stress responses in juvenile rockfish, Sebastes schlegelii, exposed to waterborne arsenic (As₃+) Jun-Hwan Kim, Ju-Chan Kang)

Selenium isn't so useful indeed, although there are some crucial enzymes containing Selenium, like glutathione peroxidase. I'll reproduce what Bienert and Tamas say about tellurium toxicity (Front. Cell Dev. Biol., 28 August 2018 Sec. Cellular Biochemistry, Volume 6 - 2018 | https://doi.org/10.3389/fcell.2018.00099):

Certain chemical Te species, such as the tellurite oxyanion (TeO₂)³⁻, are highly toxic for most organisms (Lemire et al., 2013). The molecular mechanisms of tellurite toxicity and resistance remain to be fully understood. Turner and colleagues (Vrionis et al.) investigated the effect of selenite on tellurite toxicity in the bacterium Escherichia coli. The authors found that co-exposure to selenite strongly increased bacterial resistance to tellurite. Potential mechanisms of this protective effect of selenite are discussed.

I hope it covers the toxicity of the main elements.