Written by Tringi Studies
Lead Toxicity
Lead remains one of the most discussed and studied public health topics. Both the interest and concern about lead are related to its toxicity at certain levels and doses, as well as the lack of knowledge about any biological benefits. The level at which lead exerts various effects on biological systems continues to be the focus of many studies, investigations, and debates.
It has become evident that the general public is not sufficiently informed about the health risks associated with lead. Furthermore, public health agencies responsible for issuing recommendations regarding lead exposure often provide information that is broadly “spun” by news media and the press, making this information frequently inaccurate and highly subjective regarding lead and its real risk (Daland R. Juberg, 1997).
Lead has long been one of the most studied and researched toxicants, with thousands of studies conducted on lead and its effects on both animals and humans. Unsurprisingly, numerous effects have been reported, including neurotoxicity, cardiac toxicity, reproductive toxicity, and developmental effects (Goyer, 1993).
The General Effects of Lead on Humans and Animals
At a global level, the continuous pollution by lead (Pb) has been considered a major threat to human health due to exposure through multiple pathways. The scientific literature regarding the potential harmful health effects of Pb is mainly linked to human exposure through consumption, occupational exposure, or dermal contact. Lead exposure primarily occurs when Pb dust or fumes are inhaled or when Pb is ingested through contaminated hands, food, water, cigarettes, or clothing.
The lead that enters the digestive and respiratory systems is released into the bloodstream and distributed throughout the body. However, data regarding Pb exposure (all possible human exposures to Pb , including diet, lifestyle, and endogenous sources) are much more limited. (Natasha, 2020)
Lead enters the body through various routes, such as inhalation of Pb-laden dust carried by the wind, ingestion of soil contaminated with Pb , drinking water contaminated with Pb , and consumption of food grown in areas polluted with Pb. The accumulation of Pb in animal tissues may also pose a major health risk to humans through the consumption of animal meat. After absorption, Pb is distributed in the body via red blood cells. (SJS, 2002)
Lead is a major neurotoxin. Neurotoxicity is more prominent in children and infants than in adults due to the incomplete development of the blood-brain barrier. Nevertheless, the majority of children with lead poisoning are asymptomatic. The neurological manifestations/complications of lead poisoning include acute encephalopathy, peripheral neuropathy, hearing loss, and neurobehavioral deficits such as hyperactivity, withdrawal, developmental delay, lower intelligence quotient scores, higher academic failure, and lower lifetime achievements. (Evens A, 2015)
Other clinical manifestations or complications include abdominal pain, constipation, growth retardation, vitamin D deficiency, anemia, and nephropathy. (M.D. Herbert L. Needleman, 1978)
Effects of Lead on the Locomotor System
Almost all organ systems in our body are sensitive to lead exposure. Even at a very low concentration, such as 5 micrograms per deciliter, exposure to lead can affect our tissues.
It can influence the normal functions of our body, such as bone growth, tooth development, and the mineral content of bone tissue; it can also affect the mechanisms of healing or fracture repair.
It will delay or completely stop these processes in the body. It may also impair the functioning of motor nerves.
The presence of lead in the body affects all cells, organs, and systems, disrupting their normal functions and causing lethal effects on the reproductive system, nervous system, and excretory system.
The main storage site of lead in our body is the skeleton. About 95% of the lead is present in the skeleton. Between 40–70% of the lead found in the blood is released from skeletal stores and can cause diseases such as endocrine diseases related to menopause, like thyrotoxicosis. During these conditions, lead is released back into the bloodstream. (Asghar, 2021)
Effects on the Skeleton and Teeth
As a divalent cation, lead (Pb) exhibits a strong affinity for the calcified tissues of the skeleton and teeth. It has been shown that lead levels in dentin and enamel formed before and after birth are related to the blood lead levels at the time of their formation. Lead levels in teeth have also been used as an indicator of lead exposure in adults. (Aurora M., 2006)
Bones are not homogeneous tissues, and there are differences in the sequestration of lead. Due to its low turnover rate, lead in cortical bone may have a longer half-life compared to that in trabecular bone, meaning the distribution of lead in bones is non-uniform. (Lanocha, 2013)
Effects on the Skeleton—Reduction of Motor Abilities
Exposure to lead can disrupt nerve conduction in both young and elderly individuals. Interruptions of fine motor skills have been observed in children who suffered from lead intoxication. Later in life, lead exposure precedes the curved relationship between lead levels and reaction time. Lead also reduces hemoproteins like cytochrome , which results in damage to cellular energy by suppressing myelin and impairing nerve conduction. Neuropathy caused by lead contributes to major and important skeletal problems, such as changes in walking or increasing the risk of falling (this issue still remains to be clarified). (Hiatenan, 1982)
Osteoarthritis
A comprehensive study on how lead may affect joints has not yet been conducted; however, a large number of different clinical case studies and research show a connection between lead exposure and joint pain and degeneration. In addition, the essential molecular components of joints show susceptibility to lead. (Jonathan D. Holz, 2007)
Lead smelter workers, construction workers, lead-acid battery manufacturers, and welders who have acquired higher blood lead levels exhibit an increased tendency toward arthralgia and joint stiffness.
One study identified a new link between blood Pb levels and the presence and severity of knee osteoarthritis. These observations were noted in both men and women and among African Americans and Caucasians. This research either suggests a direct toxic effect of Pb on joint tissues or an indirect effect due to increased Pb release from secondary bone remodeling. According to this study, lead may represent a new risk factor for patients with osteoarthritis. (Nelson, 2011)
The Effects of Lead on Skeletal Development
Among the well-known effects of lead during development is the stunting of skeletal growth in children. Furthermore, it is known that lead delays fracture healing and may contribute to osteoporosis. However, the exact mechanism by which lead affects normal cellular functions in bone and cartilage remains poorly understood.
A new study reports the in vitro and in vivo effects of lead on cell signaling during the differentiation of embryonic stem cells destined to form bone and cartilage. The authors exposed murine mesenchymal cells to lead in vitro and observed signaling changes in several active proteins involved in chondrogenesis: transforming growth factor beta (TGF-β), bone morphogenetic protein (BMP), activator protein 1 (AP-1), and nuclear factor kappa B (NFκB). They also implanted BMP-2-expressing mesenchymal cells into the thighs of live mice. Before implantation, the mice were exposed to lead through drinking water.
Chondrogenesis is the process by which a mesenchymal cell — a type of stem cell already committed to becoming connective tissue or blood cells — transforms into a cartilage cell, or chondrocyte. As chondrocytes mature, they further differentiate into bone and more specialized types of cartilage. Since the early embryo creates a cartilage model of the skull, spine, and limbs, chondrogenesis is vital for full skeletal development.
Given the importance of cartilage in both embryonic development and fracture repair later in life, stimulating chondrogenesis might seem beneficial; however, if lead causes excessive cartilage formation at the wrong time or prevents its further maturation into bone, it could explain the crippling effects of lead on the skeleton. Furthermore, because mesenchymal cells can differentiate into various other cell types beyond cartilage, lead might also influence the development of other body systems. (J., 2007)
Musculoskeletal Disorders in Workers Exposed to Lead
Pb can enter workers’ bodies through inhalation and ingestion. Inhalation is the primary route of exposure in Pb-related occupations. Once inside the body, Pb accumulates in erythrocytes, soft tissues (brain, kidneys, and bone marrow), and mineralized tissues (bones and teeth).
The literature states that workers exposed to Pb from battery manufacturing plants have reported disturbances in their epigenetic status, oxidative DNA damage, altered reticulocyte counts, and oxidative stress; Pb also affects several body systems, including blood pressure, ocular changes, coagulation, osteoporosis risk, poor dental health, hearing loss, cardiovascular issues, neuropathy, and renal, hepatic, and reproductive abnormalities.
Musculoskeletal components such as motor skills, bone growth and development, teeth, fracture healing, bone density, and joint maintenance are sensitive to Pb. (Kuruvilla A, 2006)
The prevalence of back pain, muscle fatigue, myalgia, and paresthesia has been reported among workers from stamping operations and lead battery factories. Musculoskeletal disorders (MSD) among Pb battery manufacturing workers were found to be significantly associated with blood lead levels.
A recent study reported a high prevalence of limb pain, limb weakness, and numbness among these Pb workers. Furthermore, in cases of severe Pb poisoning, generalized weakness predominantly affects the proximal limbs. It is well-documented in the literature that Pb exposure increases the expression of inflammation. (Singamsetty, 2017)
Conclusion
Due to its continuous use, environmental presence, and re-release from skeleton stores, lead exposure remains a risk.
The long-held belief that the skeleton is immune to lead toxicity has been overturned.
In fact, current research shows that the locomotor system may be among the most sensitive.
This sensitivity arises from:
The bioaccumulation of lead in bones, surrounding tissues, and joints, and
The prolonged retention of lead (20–30 years), resulting in chronic exposure.
Furthermore, nearly all elements of the musculoskeletal system exhibit sensitivity to lead, and the skeleton remains vulnerable to lead toxicity throughout all stages of development.
References
Asghar, M. A. (2021, May 24). Effect of lead on the musculoskeletal system. Biohavoc. https://biohavoc.com/effect-lead-musculoskeletal-system/
Aurora, M., & Klaassen, E. (2006). Lead exposure and teeth: A review. Science of the Total Environment, 367(1), 55–62. https://doi.org/10.1016/j.scitotenv.2005.11.002
Evens, A., Hryhorczuk, D., Lanphear, B. P., Rankin, K. M., Lewis, D. A., Fornoff, J., & Rosenberg, D. (2015). The impact of low-level lead toxicity on school performance among children in the Chicago Public Schools: A population-based retrospective cohort study. Environmental Health, 14(1), 21. https://doi.org/10.1186/s12940-015-0012-4
Goyer, R. A. (1993). Toxicological profile for lead. U.S. Department of Health and Human Services, Public Health Service.
Hietanen, E., & Aitio, A. (1982). Lead toxicity and its effects on motor and nerve function. Toxicology, 24(2), 121–128. https://doi.org/10.1016/0300-483X(82)90007-7
Juberg, D. R., & Kleinman, G. L. (1997). Lead and human health. American Council on Science and Health (ACSH).
Barling, V. J. (2007). Baring Bone’s Secrets: Understanding How Lead Exposure Affects Skeletal Development. Environmental Health Perspectives, 115(9), A464–A471. https://doi.org/10.1289/ehp.115-a464
Holz, J. D., & Schwartz, T. J. (2007). Environmental agents affect skeletal growth and development. Environmental Health Perspectives, 115(9), 41–50. https://doi.org/10.1289/ehp.9883
Kuruvilla, A., & Pillai, V. (2006). Clinical manifestations of lead workers of Mangalore, India. Toxicology and Industrial Health, 22(9), 405–413. https://doi.org/10.1191/0748233706th263oa
Lanocha, N., Kalisinska, E., Kosik-Bogacka, D. I., Budis, H., Sokołowski, S., & Bohatyrewicz, A. (2013). The effect of environmental factors on the concentration of trace elements in hip joint bones of patients after hip replacement surgery. Annals of Agricultural and Environmental Medicine, 20(3), 487–493.
Needleman, H. L. (1978). Preventing lead poisoning in young children. The Journal of Pediatrics, 93(5), 709–720. https://doi.org/10.1016/S0022-3476(78)80669-4
Natasha, D. C. (2020). Lead in plants and the environment. Springer.
Nelson, A. E., Liu, F., Ward, R. J., Golightly, Y. M., Jordan, J. M., Schwartz, T. A., & Renner, J. B. (2011). Whole blood lead levels are associated with radiographic and symptomatic knee osteoarthritis: A cross-sectional analysis in the Johnston County Osteoarthritis Project. Arthritis Research & Therapy, 13(2), R37. https://doi.org/10.1186/ar3272
Sandstead, H. H., & Freeland-Graves, J. H. (2002). Nutritional components modify metal absorption, toxic response, and chelation therapy. Journal of Nutritional and Environmental Medicine, 12(1), 53–67. https://doi.org/10.1080/13590840220129855
Singamsetty, B., & Rao, A. V. (2017). A study on the health profile of workers in a battery factory with reference to lead toxicity: A six-month study. International Journal of Community Medicine and Public Health, 4(5), 1463–1467. https://doi.org/10.18203/2394-6040.ijcmph20171748
Disclaimer: This article is for informational purposes only and does not constitute medical advice. Always seek the guidance of qualified health professionals regarding any concerns about lead exposure or health issues.