Rabeea Khan, MD (00:05):

Hello. I'm Dr. Rabeea Khan, Assistant Professor of Environmental Medicine and Public Health at the Icahn School of Medicine at Mount Sinai in New York. Welcome to this podcast series on occupational medicine. Today's episode is focused on lead exposure. Let's begin with a background on heavy metals.

Heavy metals are generally defined as metals with a relatively high density atomic weight or atomic number. The criteria used vary depending on context. Certain metals such as zinc, copper, chromium, cobalt, and manganese are essential for normal metabolism. Others such as lead, mercury, arsenic, and cadmium, and these are the ones we'll talk about, serve no recognized biological purpose. Effects of a heavy metal depend on the route of exposure, whether it's dermal, inhalational, ingestion or injection, the form of exposure so if the metal is in its elemental form, inorganic form, or organic form, the dose and the duration of an exposure so acute one-time, short-term at a high dose versus chronic, regularly repeated, long-term exposure at a low dose will have different effects.

Heavy metals can affect most organ systems, which we will talk about as we go through them one by one. Let's begin with lead. Lead is a blue, gray, soft metallic element that occurs naturally in small amounts in the earth's crust. It's a malleable metal so it can be easily worked with. You can hammer it into protective sheets so make pipes and bend them easily. It's dense and has good shielding protection against radiation so it's used to shield against penetrating forms of ionizing radiation. Lead is insoluble in water but some of the salts do dissolve so lead salts can be carried long distances in water supplies. It has a low melting point and lead fumes will easily be formed when lead is heated. Lead can be formed into organic compounds by some organisms and some organic compounds like leaded gasoline have had industrial uses in the past.

There are different definitions of what is considered an elevated lead level, depending on the context and the regulatory body. NIOSH, CDC's Adult Blood Lead Epidemiology and Surveillance Program, defines elevated blood lead levels for an adult is greater than five micrograms per deciliter. The CDC also uses five micrograms per deciliter threshold for elevated blood lead levels in children. However, the current OSHA standard allows workers to continue working up to a blood lead level of 40 micrograms per deciliter. For context, a well-balanced diet provides less than 10 micrograms of lead per kilogram of body weight per day. Bone is the body's largest storage depot of lead and a bone meal can have 100 micrograms of lead per gram of bone. By contrast, bottled baby food has about 3.5 micrograms of lead per liter of baby food.

Uncontaminated soil in a remote area away from industry may have only a small amount, as little as two micrograms of lead per gram of soil in it. But in areas where lead is naturally abundant in soils there may be as much as 200 micrograms of lead per gram of soil. In contrast, even though it's been years since the ban on leaded gasoline in US urban residential areas near busy roads or factories, can have over 500 micrograms of lead per gram of soil. By far, the greatest oral source of lead is ingestion of either paint chips or dust that contains paint. Paint chips can have up to 40% or even more lead by weight. There are a lot of occupational exposures as well because lead remains a component of many useful products.

Examples include batteries, circuitry, medical shielding devices, gasoline in some developing countries, cans and ceramic glazes, again, when regulatory control is poor, cable coatings, for example as a plasticizer and the plastic coating on your phone line, some types of printing, brass, and bronze manufacturing, galvanized metals and metal plating, some ceramics and even insecticides. Lead is used extensively in ammunition in both the explosive and to add weight to the bullet. Workers engaged in the manufacture, use, reclamation or recycling of any of these common products may be exposed to lead. There are some distinctly unusual sources of oral exposure to lead that are worth mentioning. Historically, moonshine whiskey made in lead glazed bots or even radiator coils was a source of lead poisoning. Ceramic vases and glazed pottery are an important source of population lead poisoning internationally, in Mexico for example.

Lead crystal is expensive and beautiful yet materials such as fruits and wines, cherries and other alcoholic beverages can leach some of the lead from the crystal. Folk remedies and cosmetics of certain ethnic groups contain lead. For example, coal which is used in the South Asian region. Lead has been found in the wicks of certain kinds of candles. All of these unusual sources together are far less important in the United States than lead from paint and in the soil. There are two key developments in the late 19th and 20th century that are responsible for most of the environmental exposure to lead; the addition of lead to paint, which was done because it improves the long-term adhesion of paint to surfaces, especially in exterior surfaces, and the use of lead as a fuel additive in leaded gasoline, which happened in 1923. Lead, when added to gasoline, improves the refining and octane performance of gasoline.

In the US, we have largely reversed the problems of lead by policy change. Lead was banned in paint in 1978 and the use of leaded gasoline ended in the United States in the 1970s with the Clean Air Act, and most other developed countries and many developing countries have followed suit. Respiratory exposure is a primary source of exposure in adults. Adults breathe in dust or fumes that contain lead, usually an occupational source. Typically, 30 to 50% is absorbed through the lungs and then absorbed lead is distributed via the pulmonary circulation to other parts of the body via the bloodstream. Oral ingestion is the main route of exposure in children. For example, ingesting of paint chips or dust. An estimated six to 10% of ingested soluble lead is absorbed in adults compared to approximately 40 to 50% in young children.

Pregnant women are also more likely to absorb lead more efficiently when ingested. Why is it different in adults versus children? Children and pregnant women are supporting bone development. Lead is more likely to be absorbed when the gut is primed to absorb iron and calcium. Kids are avid to absorb calcium so they will also absorb lead. An interesting aspect of the absorption of ingested lead is how it can vary depending upon metabolic status. A well fed adult might absorb 6% of an ingested lead dose, a fasting adult might absorb more. Iron deficiency in low calcium diets may increase gastrointestinal absorption. Skin is relatively impermeable to lead. Organic lead is different. Like many organic metals, organic lead is readily absorbed through the skin and taken into organs more rapidly, which is very dangerous. Regardless of the route of exposure, lead is absorbed into the bloodstream. Blood lead levels peak in several days following exposure. Some lead is incorporated into the building of hemoglobin molecules in red blood cells.

The half-life of lead in blood is approximately equivalent to the half-life of red blood cells, so around one month. With acute exposure, half will be gone in 30 days. Next, lead travels to soft tissues such as kidneys, lungs, brain, spleen, muscles and heart. This occurs within a matter of days. After several weeks, most lead which is not excreted, approximately half of the absorbed lead, moves into the long term storage areas which are the bones and teeth. About 94% of an average adult's total lead burden so the total amount of lead in all tissues throughout the body is in the bones and teeth. In children, this is about 70%. While the half-life of lead in the adult red blood cells in the order of 30 days, it is decades in bones. It will take more than 10 years to turn over one-half of the body stored lead. In patient with a high burden of lead and bone, slow redistribution to the blood will continue to elevate blood lead concentrations for years after exposure ceases.

Lead is excreted from the body by various routes, principally in the urine about 70%, but also in secretions such as breast milk, sweat, stools. This has implication for women who are planned to be pregnant if they have a high body burden of lead. Nursing mothers who have been lead poisoned even in the remote past may need to get their breast milk tested. Lead affects many different organ systems, including the nervous system, reproductive system, hematologic, GI, endocrine, and renal systems. Lead exerts its toxic effects by interfering with the action of essential cations such as calcium, zinc, iron and macromolecules, enzymes receptors, membrane transcription factors in cells throughout the body. This leads to changes in mitochondrial and cellular membranes, neurotransmitter synthesis and function, nucleotide metabolism, and endocrine signaling.

Anemia is common because lead inhibits synthesis of hemoglobin by inhibiting enzymes so you have decreased insertion of iron and production of free protoporphyrins. The anemia you see is generally not so severe. The hemoglobin and hematocrit will be down a few points. It's normochromic and normocytic initially, and then hypochromic microcytic later on. The classic finding is basophilic stippling on red blood cells from hemoglobin or porphyrin deposition from the non-insertion of iron. Lead causes a distal, primarily axonal, with secondary myelin damage symmetric polyneuropathy. [inaudible 00:10:09] is detectable on nerve conduction testing although patients frequently complain of more severe symptoms on one side. The perineal and radial nerves are often affected and the resultant wrist and ankle weaknesses are sometimes called lead palsy.

The peripheral neuropathy of lead poisoning poses a special acute risk to bridge construction and shipyard workers who often perform their jobs at heights. Hand and foot weakness, large joint pain, problems with tactile perception in feet and joints, and ataxia pose additional risk in this circumstance. Chronic renal effects include hypertension, nephropathy from chronic proximal tubule dysfunction, hyperuricemia, and gout. This results from direct effects on the kidney and vascular smooth muscle. Lead is a reproductive toxin for both sexes and male symptoms include diminished libido, decreased sperm production, decreased sperm motility, and abnormal sperm. Morphology. Lead crosses the placenta in plasma. The likely sources of placental lead originate in maternal bone stores which are mobilized along with calcium in pregnancy.

Lead is associated with spontaneous abortion in early pregnancy. There is clear evidence of cognitive dysfunction including reduced IQ and learning disabilities in children and some evidence for gestational hypertension, pre-term delivery, and low birth rate in middle and late pregnancy. Symptoms depend on the amount of exposure. With lower exposure, patients may complain of fatigue, anorexia, irritability, and headaches. With higher levels, paresthesias, tremors, decreased cognitive function, and GI symptoms are noted. Encephalopathy is seen with acute exposures greater than 90 to 100 micrograms per deciliter range. Exam findings include high blood pressure, change in sensation, proprioception, vibration sense changes, and wrist drop. With chronic exposure, blue-black gum lead lines have been described. This is due to the reaction of lead with bacteria and dental plaque that causes formation of lead sulfide. However, these are rarely seen today.

Key aspects of the clinical history that are essential for diagnosis include asking about the nature of the household environment, especially paint in the house and any other environment where time is spent. For example, at a family member's house or a babysitter's house. Home remodeling activities, drinking water source and type of pipe, proximity to industrial emission source or unleaded gasoline use, time spent elsewhere than in the home and environmental conditions there, hobbies of all family members, use of imported or glazed ceramics, unusual medicine use, unusual cosmetic use, herbal supplements. Of course, an adult occupational history should be taken, with specific questions about tasks and materials, presence of job activities such as burning, sandblasting, sanding or chipping.

When lead exposure is suspected from history, one should obtain a blood lead level. It is important to remember that it only reflects recent exposure since the half-life of lead in blood is around 30 days or the release of endogenous lead from bone and soft tissues. Erythrocyte protoporphyrin, which is a hemoglobin precursor, is often measured as zinc protoporphyrin or ZPP, becomes elevated with lead exposure greater than 25 micrograms per deciliter. Because there's a time lag of weeks with elevation of ZPP due to lead exposure, a blood lead level of, for example, 40 micrograms per deciliter with a normal ZPP suggests more recent lead exposure. However, ZPP is elevated in other conditions such as iron deficiency anemia, and the test is neither sensitive or specific for detecting detecting lead exposure.

X-ray fluorescence is a non-invasive method to assess for cumulative lead exposure by measuring bone lead concentration but is primarily used for research and is not readily available. Exposure history is important as it is the key to the most effective treatment, which is removal from exposure. Otherwise, it is to prevent exposure via substitute of products, engineering controls, changes in workflow and practices, and the use of personal protective equipment. Chelation therapy can be considered with blood lead levels greater than 80 to 100 microgram per deciliter range, or if symptomatic with blood lead levels greater than 50 micrograms per deciliter. The two most common chelating agents for adults are succimer and calcium disodium ethylene diamine tetra acetic acid, or EDTA. It's generally not recommended with blood lead levels under five 50 micrograms per deciliter.

Chelation should be considered after identifying the exposure because with continued exposure chelation will cause increased lead absorption. Ongoing surveillance depends on many factors, such as the initial lead levels, whether or not exposure is ongoing, and it's beyond the scope of this review. OSHA has set federal regulations as well to protect its workers. However, early detection and prevention are key to protecting patients from the harmful effects of lead exposure. Thank you for participating in this activity. Please continue on to answer the questions that follow and complete the evaluation.