Main routes of lead exposure and health effects


The health impacts of lead exposure, including low-level exposure, have been extensively reviewed and are summarized here (ATSDR, 2007; JECFA, 2011; NTP, 2012; Health Canada, 2013). Young children, pregnant women and women of childbearing age are particularly vulnerable to the toxic effects of lead.

Routes of exposure to lead3

The main routes of exposure and absorption of lead are inhalation, ingestion and, to a much lesser extent, dermal contact (ATSDR, 2007). Inhalation of fumes and dust is a major route of exposure for people working with lead. Young children are particularly likely to be exposed through contaminated soil and air-borne household dust because they spend a lot of time in one place, tend to play on the ground, and have frequent hand-to-mouth activity (WHO, 2010a). Children with pica, a compulsion to eat non-food substances, may persistently eat lead-contaminated soil (Mielke & Reagan, 1998). Lead exposure may also occur from consumption of contaminated food and water. 

The absorption of lead from the gastrointestinal tract is affected by dietary factors, age and nutritional status (JECFA, 2011). Infants and young children absorb proportionately more lead than adults, typically absorbing around 50% of ingested lead compared to around 10% in adults (WHO, 2010a). The absorption of lead is also greater in people with dietary deficiencies of iron or calcium, which may be widespread in economically deprived communities. 


Once absorbed, lead is distributed to most organs of the body, including the central nervous system, liver and kidneys, but the largest proportion (up to 90% in adults) is stored in bone (Barry, 1975). Lead accumulates in bone over life up to age 50 to 60 years, followed by a decline due to age-related changes in diet, hormonal concentrations and metabolism (Mushak, 1993). There is an equilibrium between the amount of  lead in blood and bone, and some lead is gradually released back into blood over time (Rabinowitz, 1991). Lead in bone does not cause toxic effects but it becomes a potential source of toxicity when metabolic changes cause more rapid release. 

This can occur during pregnancy, lactation, the menopause and following bone fracture (Silbergeld et al., 1988; Markowitz & Weinberger, 1990; Mushak, 1993; Gulson, 2003). If the blood lead is reduced, e.g. following chelation therapy, some lead will be released from bone to restore the equilibrium. Lead readily crosses the placenta exposing the fetus. The lead concentrations in maternal and fetal blood are similar (Graziano, 1990; WHO, 1995). Lead is present in breast milk from external sources of exposure or remobilized from skeletal stores, though the concentrations in breast milk are low (Ettinger et al., 2004; Ettinger et al., 2014)

Toxic effects of lead

Lead has no apparent physiological function. It has an affinity for sulfhydryl groups and other organic ligands in proteins and can mimic other biologically essential metals, such zinc, iron and, in particular, calcium (Health Canada, 2013). This enables lead to disrupt enzyme systems dependent on these ions, accounting for many of its toxic effects (Lidsky & Schneider, 2003; Garza et al., 2006).

 The toxic effects of lead are wide-ranging and affect almost all body systems. Acute lead poisoning from a single exposure is relatively rare and chronic poisoning is more common; however, the clinical features of poisoning are similar in both cases. The presenting signs and symptoms are very variable in both adults and children and may include gastrointestinal, haematological and neurological effects. Young children are particularly vulnerable to the neurological toxicity of lead and this is the main reason that lead is of public health concern.

 Lead also has toxic effects on the reproductive, endocrine and cardiovascular systems. Important toxic effects are summarized below by body system. The duration of illness in lead poisoning may be long and periodic, requiring the monitoring of blood lead concentrations and repeated courses of antidotal chelation therapy


Gastrointestinal effects

Gastrointestinal effects are common in lead toxicity and may be the reason that an exposed person first seeks medical attention. The effects include loss of appetite with weight loss, constipation, abdominal pain or discomfort, nausea, vomiting and a metallic taste in the mouth. Diarrhoea occurs occasionally (Winship, 1989). Lead colic (intense, painful, intermittent abdominal cramps)

is associated with severe constipation and vomiting, and can be mistaken for other conditions such as appendicitis, peptic ulcer, pancreatitis or intestinal obstruction (Janin et al., 1985). Gastrointestinal bleeding has occasionally been reported (McNutt et al., 2001; Frith et al., 2005). Patients with poor dental hygiene may have a ‘lead line’ (Burton or blue line) along the gums (ten Bruggenkate et al., 1975). This line is composed of dark granules of lead sulfide precipitated by the action of hydrogen sulfide (from bacterial degradation of organic matter) on lead. There may also be grey spots on the buccal mucosa and on the tongue (ten Bruggenkate et al., 1975).



Neurological effects  

Lead exerts toxic effects in all parts of the nervous system. Lead poisoning can cause life-threatening encephalopathy (disruption of brain function), particularly in young children. Encephalopathy is less commonly seen in adults (ATSDR, 2007). Initial signs include sporadic vomiting, loss of appetite, behavioural changes with aggression, irritability and agitation, headache, clumsiness and intermittent lethargy. 

This may progress to persistent vomiting, ataxia, convulsions, severe cerebral oedema, raised intracranial pressure, coma and death. Lead encephalopathy is a life-threatening condition and children can be left with mental retardation, seizure disorders, blindness and hemiparesis (weakness of the entire left or right side of the body) (Perlstein & Attala, 1966; Chisolm & Barltrop, 1979; Al Khayat et al., 1997). Such severe impacts are now relatively uncommon in developed countries but can still be seen in places where there are high levels of exposure and limited or no access to diagnosis and treatment (Haefliger et al., 2009; Greig et al., 2014). 

Analysis of a large case series of lead-poisoned children in Nigeria found that concurrent infection with malaria increased susceptibility to the neurotoxic effects of lead (Greig et al., 2014). Chronic lead toxicity may also cause more subtle changes in neurological function in children and adults. There is a large literature on the neurodevelopmental toxicity of lead in children (Lidsky & Schneider, 2003; Bellinger, 2004a; Koller et al., 2004; Needleman, 2004; NTP, 2012). 

The effects include reduced cognition and behaviour scores, changes in attention (including attention deficit hyperactivity disorder), impaired visual-motor and reasoning skills, and impaired social behaviour and reading ability. Some of these effects have been found to persist into later childhood and adulthood (Needleman et al., 1990; Fergusson & Horwood, 1993; White et al., 1993; Tong et al., 1996; Fergusson et al., 1997; Tong, 1998; Tong et al., 1998; Stokes et al., 1998). Delinquent behaviour has also been associated with lead exposure (Needleman et al., 1990; Needleman et al., 1996; Dietrich et al., 2001; Wright et al., 2008). Poor scores for social/ emotional functioning have been reported in preschool children (Mendelsohn et al., 1998).

Even low levels of exposure, and blood lead concentrations below 5 µg/dL, can be associated with neurological damage in children (NTP, 2012). Indeed, studies to date suggest that there may be no threshold blood lead concentration for neurotoxic effects in children and that the association between blood lead concentration and IQ may be non-linear (JECFA, 2011).

 A pooled analysis by Lanphear et al. (2005) found a steeper decline in IQ in children with maximal blood lead concentrations below 7.5 µg/dL compared with those having maximal blood lead concentrations above 7.5 µg/dL. In adults, case reports and small studies describe a higher incidence of malaise, forgetfulness, headache, fatigue, lethargy, irritability, dizziness and weakness in occupationally exposed adults (ATSDR, 2007). 

Lead exposure may also be associated with a greater risk of neuropsychiatric and neurobehavioural problems (Valciukas et al., 1978; Williamson & Teo, 1986; Stollery et al., 1991; Chia et al., 1997; Bleecker et al., 2005; Chen et al., 2005; Schwartz et al., 2005). Lead can cause both motor and sensory neuropathy. In individuals with severe, chronic lead toxicity wrist drop and foot drop (inability to extend the wrist or foot) may be seen. 

These effects are more commonly observed in adults than children with lead toxicity (ATSDR, 2007). Motor weakness usually resolves once the individual is removed from exposure but this may not be the case with sensory neuropathies (Rubens et al., 2001). Poor postural stability has been reported in children with mildly elevated blood lead concentrations (Bhattacharya et al., 1990) and in lead-exposed workers (Chia et al., 1996; Ratzon et al., 2000; Iwata et al., 2005). Lead may also cause visual impairment and reduced hearing (Cavalleri et al., 1982; Otto & Fox, 1993; Rothenberg et al., 2002). Hearing impairment in children may occur even with blood lead concentrations below 10 µg/dL (NTP, 2012).


Cardiovascular

Lead exposure is associated with an increased risk of hypertension in adults and pregnant women, even at levels of exposure below 10 µg/dL (NTP, 2012). Significant, though modest, associations have been found between lead concentrations in blood and bone and blood pressure (Cheng, 2001; Nawrot et al., 2002; ATSDR, 2007). The association is stronger with bone lead, suggesting that the increase in blood pressure is related to the long-term effects of lead exposure earlier in life (Cheng, 2001; Gerr et al., 2002). 

Renal

Lead can cause damage to the renal tubules with impairment of renal function; however, acute renal damage is usually reversible (Green et al., 1976; Chisolm & Barltrop, 1979); Wedeen, 1988; Loghman-Adham, 1997). Chronic lead exposure may cause a progressive nephropathy (Loghman-Adham, 1997). The onset of lead-induced renal impairment is subtle and patients may remain asymptomatic until there is significant renal dysfunction (Loghman-Adham, 1997). Even low levels of exposure to lead can be associated with abnormalities in renal function (NTP, 2012).

Endocrine 

Environmental lead exposure has been associated with delays in sexual maturity in girls (Selevan et al., 2003; Wu et al., 2003; NTP, 2012). Lead exposure has also been associated with delays in growth and reduced growth (e.g. smaller stature, smaller head circumference) in children (NTP, 2012).

Reproductive system and pregnancy 

Impotence and decreased libido are occasionally reported in lead-poisoned patients (Cullen et al., 1983). Reduced fertility has been found in couples during periods when the blood lead concentration in the male is elevated (JECFA, 2011). Possible causes include reduced sperm motility, decreased sperm count and reduced semen volume (NTP, 2012). Lead has long been known to be harmful in pregnancy and has been used as an abortifacient (Bastrup-Madsen, 1950). Maternal lead exposure, even at low levels, may be associated with reduced fetal growth, lower birth weight, preterm birth and spontaneous abortion (NTP, 2012; Health Canada, 2013). Lead exposure is a risk factor for hypertension in pregnancy (gestational hypertension) and high levels of exposure may be a risk factor for pre-eclampsia, which can be life-threatening for both the mother and baby (Troesken, 2006; CDC, 2010).

Haematological

High levels of exposure to lead reduce the synthesis of haem, which is necessary for the production of red blood cells, resulting in anaemia (ATSDR, 2007). Coarse basophilic stippling of red blood cells may be seen, though this is not found in all patients with lead poisoning. Interference with haem synthesis also has other negative impacts, for example haem is needed for the formation of cytochrome c, which is essential for cellular respiration, and this may contribute to the neurotoxicity of lead (ATSDR, 2007).

Toxic effects in relation to blood lead concentrations

The most widely used method for assessing exposure to lead is the measurement of lead in whole blood (see section 6.1). There is, however, considerable interindividual variation in the blood lead concentration at which specific signs of poisoning manifest. Some individuals may apparently be clinically well at blood lead concentrations that are associated with encephalopathy in others

(Bellinger, 2004a). This also applies to subclinical effects such as effects on IQ, meaning that children with the same blood lead concentration do not necessarily have the same risk of impaired neurodevelopment (Bellinger, 2004a). Table 1 summarizes information on toxic effects that have been reported at specific blood lead concentrations and illustrates some of the variability in response.


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