Lead Toxicology

University Degree Subjects allied to Medicine

Mubeen Iqbal How much lead is too much?

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Module Code: BMSC 2214

Module Title: Introduction to Toxicology

Essay Title: How much lead is too much?

Name: Mubeen Iqbal

SID: 200242757

Word Count: 1558

How much lead is too much?

Introduction

Lead is a toxic, soft, malleable metal with four isotopes. It exists in organic and inorganic forms, its atomic number is 82 and it has the symbol Pb. Lead is found in ore with zinc, silver and copper. The most common lead ores are galena, cerussite, and anglesite. The melting point of lead is 327 oC, it is very resistant to corrosion, and it is a poor conductor of heat and electricity. These are some of the main properties which have led to the extensive use of lead for thousands of years. Currently lead is used in battery acid, organ pipes, weights, bullets and for many other functions and purposes. In the past lead was also used in plumbing, in the manufacture of toys, in alcohol, in paint, and most notably, in leaded fuel. However these former uses have almost all now been discontinued, in the Western world at least, due to the increasing recognition of the health risks and the toxic effects of lead.

Lead toxicity is thought to have first been recognised by the Greek physician Nicander of Colophon, who described the detrimental effects of lead ingestion in his books, which are the oldest to have survived on the subject of poisoning (Needleman, 2004). Mathieu Orfila, who is widely regarded as the founder of modern toxicology, stated in his book of 1817 ‘A General System of Toxicology’: ‘If we were to judge of the interest excited by any medical subject by the number of writings to which it has given birth, we could not but regard the poisoning by lead as the most important to be known of all those that have been treated of, up to the present time’ (Orfila, 1817, cited in Gilbert and Weiss, 2006).

Entry, absorption, deposition, and elimination of lead

Lead can enter the body in one of two ways: it can be ingested via contaminated hands, clothing, water, or food, or it can be inhaled in the form of fumes or dust. Lead entering the body is most efficiently absorbed by the respiratory tract; particles of lead which have a diameter of 1μm or less are completely absorbed by the alveoli. Lead is also absorbed by the gastrointestinal tract following ingestion but this is less effective. The toxic effects of lead are mostly attributed to deposition in erythrocytes, to which 99% of absorbed lead binds. The remainder of the lead enters into bone and soft tissue. The half-life of lead in the body differs across the various parts of the body where it is deposited. In erythrocytes it is approximately 35 days, in soft tissue it is approximately 40 days, and in bone the half life can be up to several decades (Roth and Staudinger, 1998). Elimination from the body of any lead which is not retained occurs through the excretion of urine and, to a lesser extent, bile.

Mechanisms of lead toxicity and resulting symptoms

Once in the body, lead interacts with ions and molecules, such as iron, zinc, and calcium, causing dysfunction in various enzyme catalysed reactions. Cell membranes and mitochondrial membranes are also disturbed by lead, as is the sodium-potassium pump. Lead poisoning therefore affects almost all major organs of the body. The most widely studied effect of lead poisoning is the reduction of haem synthesis, by means of inhibition of delta aminolevunilic acid dehydrase (delta-ALAD) and ferrochelatase (FECH). The lysis of red blood cells also occurs when lead binds to their membranes. Another ...

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Mechanisms of lead toxicity and resulting symptoms

The most critical effect of lead toxicity on the body is the effect on the nervous system. Lead poisoning causes oedema in the brain by affecting the blood brain barrier. This leads to symptoms such as headaches, ataxia, clumsiness, vertigo, seizures, and even coma. Demyelination of neurons due to damage to Schwann cells is also caused by lead toxicity, as is the decline in function of neurotransmitters. In extreme cases, encephalopathy can also result (Goyer, 1993).

Lead poisoning also affects the gastrointestinal system by causing the smooth muscle in the wall of the tract to contract causing colic (severe abdominal pain), vomiting, diarrhoea, and anorexia.

The kidneys are also affected by lead poisoning since the excess of lead in the body causes aciduria, phosphaturia, and can also lead to gout and permanent nephrosis.

Lead also has detrimental effects on growth due to the inhibition of growth hormones, and its intervention of the functions of cyclic AMP and calcium. It also has damaging consequences on the reproductive system, resulting in abnormally low sperm count in men, and infertility, irregularities in the menstrual cycle and stillbirths in women.

Treatment of lead poisoning

The most essential aspect of treating lead poisoning is reducing the exposure to lead. Chelation therapy is also used to reduce blood lead levels. This involves administration of drugs such as EDTA and DMSA, which bind to lead and flush it out through the urine.

Lead poisoning in adults

Lead poisoning in adults occurs mainly through occupational exposure. Workers in industries such as painting, construction, steel, car manufacture and repair, scrap metal and many others are at risk of substantial exposure to lead. People employed in these industries are also likely to affect those who come into close proximity with them, via a phenomenon known as ‘take-home lead’ (Czachur et al., 1995). This is when the worker inadvertently exposes their family members or others with whom they have contact, through contaminated skin, clothes, or equipment, or even by washing polluted clothes with another person’s uncontaminated clothes.

The chief causes of acute lead poisoning in adults are the use of folk remedies containing lead, and the consumption of ‘moonshine’, a term used to refer to illicit alcohol which is contaminated with lead, due to the use of car radiators in its manufacture.

Figure 1 (Gilbert, 2004) shows the effects of lead on adults at various blood lead levels, and it also shows the effects of lead in children. Lead poisoning in children has been the subject of intense recent study due to the greater absorption, and therefore more damaging manifestations, of lead in children.

Figure 1 – Effects of lead – children vs adults.

Adapted from ATSDR, 1989 (Gilbert, 2004)

Lead poisoning in children

In contrast to lead poisoning in adults, lead poisoning in children was only first reported in 1892 in Australia (Needleman, 2004). Children are much more likely to be affected by lead toxicity than adults for a number of reasons; firstly children are more likely to put their hands in their mouth after coming into contact with lead in soil, paint, toys, or other sources, secondly their developing nervous system is more susceptible to damage than the fully developed nervous system of an adult, and thirdly the absorption of substances in the gastrointestinal tract occurs more readily than in adults. These factors mean that children are more severely affected by the symptoms discussed earlier, and these symptoms occur at lower exposure levels and lower blood lead levels than adults.

Exposure to lead toxicity in children is also significant because the vast majority of lead which enters the body is stored long-term in the bone. This lead is released in later life when bone resorption increases thus causing a sudden rise in blood lead level, resulting in the symptoms discussed earlier.

In addition to this, children who are exposed to lead at an early age are more likely to drop out of school and even become criminals in later life (Nevin, 2006) as shown in Figure 2.

Figure 2. Preschool Blood Lead vs. Broadly Defined Index Crime with a 19-Year Lag. Legend: Broadly defined index crime rates include USA index crimes plus threats, assaults without injury, and thefts below a USA monetary threshold. Despite recording differences and divergent crime trends, broadly defined index crime rates also track blood lead trends with a 19-year lag. Taken from Nevin (2006).

Figure 2 shows the increase in crime rate in four different countries as blood lead levels increased (with a 19 year lag). This evidence demonstrates the further cause for concern of the impact of low-level lead exposure on the central nervous system leading to behavioural problems.

The removal of lead from petrol has been very effective in reducing the average blood lead level of children in recent years, as this is regarded as one of the most significant and widespread exposure routes of the last century. The sale of leaded fuel was banned in the USA from January 1, 1996 by the Clean Air Act, it was banned from January 1, 2000 in the UK, and more recently, it was banned in Africa from January 1, 2006. In fact, in the USA, the average blood lead level of children went from approximately 16 μg/dL in 1976 to 3.2 μg/dL in 1994 (Gilbert and Weiss, 2006). This dramatic fall has been attributed to the removal of lead from petrol. The major remaining routes of exposure of children to lead is older housing, in which lead paint and other materials have been used in construction, and lead particles in soil and dust.

The increasing recognition of the severity of lead poisoning in children has caused recommended blood lead levels to drop as shown in Figure 3.

Figure 3. Lowering of the recommended action level for blood lead in children over time by the Centers for Disease Control and Prevention (CDC) in America.

Taken from:

However, despite the lowering of the recommended action level of blood lead to 10 μg/dL in 1991, the CDC has been under pressure from various researchers (Gilbert 2006; Bernard, 2003) to further lower the recommended action level due to extensive and growing research which suggests that exposure to lead leading to blood lead levels of even less that 10 μg/dL. For example, Canfield et al. (2003) showed ‘a loss of 7.4 IQ points for a lifetime average blood lead concentration of up to 10 µg/dL’ and concluded that ‘the total lead-related impairment … is due largely to the initial IQ loss at blood lead concentrations of 10 µg/dL or less’.

Conclusion

Despite the harmful effects of lead being recognised for thousands of years, the full extent of the severity of lead toxicity, especially in children, has only been acknowledged recently. Renowned researchers and experts in the subject, such as Needleman (2004) and Gilbert (2004), have now come to the conclusion that there is no safe limit for lead exposure, particularly for children, for whom the effects of lead toxicity have been documented to cause long term learning difficulties, severe nervous system disorders, and susceptibility to commit crime, even at extremely low levels of blood lead.

References

Books

GILBERT, S G. 2004. A small dose of toxicology: the health effects of common chemicals. Florida: CRC Press LLC

Journals

BERNARD, S M. 2003. Should the Centers for Disease Control and Prevention’s Childhood Lead Poisoning Intervention Level Be Lowered? American Journal of Public Health. 93 (8), p. 1253-1260.

CANFIELD, R L., D A. CORY-SLECHTA, C. COX, C R. HENDERSON, T A. JUSKO, and B P. LANPHEAR. 2003. Intellectual Impairment in Children with Blood Lead Concentrations below 10 µg per deciliter. The New England Journal of Medicine. 348, p.1517-1526.

CZACHUR, M., B. GERWEL, M. GOCHFELD, G G. RHOADS, M. STANBURY, and G. WARTENBERG. 1995. A pilot study of take-home lead exposure in New Jersey. American Journal of Industrial Medicine. 28 (2), p.289.

GILBERT, S G., and B. WEISS. 2006. A rationale for lowering the blood lead action level from 10 to 2 μg/dL. Neurotoxicology. 27 (5), p. 693-701.

NEEDLEMAN, H. 2004. Lead Poisoning. Annual Review of Medicine. 55. p. 209-222

NEVIN, R. 2007. Understanding international crime trends: The legacy of preschool lead exposure. Environmental Research. 104 (3), p. 315-336.

ROTH, V S., and K C. STAUDINGER. 1998. Occupational lead poisoning. American Family Physician. 57(4), p.10

Websites

ATSDR – CSEM - Lead (Pb) Toxicity - What Are U.S. Standards for Lead Levels? [online]. [accessed 6th March 2008]. Available from the World Wide Web:

< http://www.atsdr.cdc.gov/csem/lead/pb_standards2.html>

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