Lead Risk Reduction Strategy

Appendix C. Lead Toxicity

Lead is a metal of high cumulative toxicity with no known biological role. It has been recognized for centuries that lead has detrimental effects on human health. Since lead disrupts essential enzyme systems mediated by metals such as calcium, iron, and zinc, it can produce adverse effects on virtually all body systems. It has been suggested that there is no minimum level of lead exposure which will not adversely affect human health (59). The potential risks associated with lead are increased by the fact that lead accumulates both in the environment and in the bones of exposed individuals. Once present in the skeleton, lead can be re-released into the blood under certain physiological conditions.

Evaluation of lead toxicity studies is complicated because differences in study population size, age, sex, health history, exposure to other health hazards, and lead exposure history often make it difficult to compare studies. There is little controversy about the multiple adverse effects of long-term exposures to high levels of lead on the human body. Although there are significant differences of opinion in the scientific and medical communities about the effects of low-level lead exposure, especially on learning and cognition in children (20,72,74,77), the debate is usually about the extent of effects rather than whether or not effects occur. The ubiquity of lead in the human environment makes it difficult to conclude causality when investigating the effects of exposure to low lead levels. At low blood lead levels, symptoms of lead poisoning are often subtle and non-specific and the condition may not be recognized or treated.

Lead poisoning can occur in acute or chronic form. Acute lead poisoning is rare today, especially in adults. It generally manifests itself by abdominal cramps and severe pain, followed by nausea and vomiting. Headaches, confusion, seizures, coma and other symptoms of brain dysfunction may follow. Very high exposure levels may result in kidney failure (71). Though it is an extremely rare occurrence today, blood lead levels above 80 ug/dL in children can cause coma, convulsions and even death. Chronic lead exposure at lower levels can cause a variety of non-specific symptoms including loss of appetite, nausea, constipation, anxiety, fatigue, weakness, irritability, headache, insomnia, pain or soreness in the joints and muscles, numbness, tremors and dizziness. Prolonged exposures can also cause severe impairment to the neurological, gastrointestinal, renal, reproductive and blood-forming systems.

Lead is known to inhibit enzymes involved in synthesis of heme (the pigmented, iron-containing portion of the hemoglobin molecule), resulting in decreased production of hemoglobin (red blood cells). This decrease may produce anemia and may affect hepatic function, particularly in children (105). Prolonged continuous exposure to even low dosages of lead may result in subclinical renal dysfunction (56). Nephropathy associated with elevated lead blood levels has been recorded in numerous studies, although some reports have found no correlation (102).

There is a clear link between high levels of lead exposure and adverse reproductive effects, including increased rates of miscarriage and stillbirths in exposed women (65).

Some studies suggest that exposure in childhood may cause reproductive difficulties in women (102). A large study in 1996 (3) found an association between sperm abnormalities and blood lead levels around or above 40 ug/dL. There is considerable debate on whether there is a significant link between lead exposure and hypertension. The correlation is greatest for men aged 40-59, even at very low blood lead levels (57). Some studies show an association between lead exposure and abnormal ECG tests or other heart effects (102).

A study by Rosen et al. (82) showed interference with conversion of vitamin D to its hormonal form in children, accompanied by lower blood calcium levels, in children with blood lead of 33- 120 ug/dL. Lead exposure may also damage the male reproductive system and contribute to some miscarriages. Lead has been found to be a renal carcinogen at high doses in rats, but there is no definitive evidence for human carcinogenicity, although small, statistically non-significant increases in digestive and renal cancers have been recorded among occupationally exposed men, and a statistically significant link between rectal cancer and workers exposed to tetraethyl lead (27).

The best known and most studied effects of lead exposure are neurological effects. Fatigue, mood swings, apathy, dizziness, weakness, and subtle impairments in intellectual function are associated in adults with blood lead levels of 40-80 µg/dl (102). Increased exposure will result in such affects as insomnia, confusion, headaches, and memory problems as the central nervous system becomes more profoundly affected. Nausea and vomiting, diffuse abdominal pain, constipation or diarrhea, weight loss and decreased libido may also occur. Clinically, lead has been shown to affect nerve conduction at blood lead concentrations as low as 30 µg/dL (2,17,89,102). Prolonged exposure to lead degrades the nerves controlling the transmission of peripheral nerves, resulting in conditions like wrist drop and foot drop (83).

If blood lead levels are in excess of 100 ug/dL, toxic effects can progress to seizures, coma and death caused by lead encephalopathy (dysfunction of normal brain activities). Lead encephalopathy, though a relatively frequent occurrence prior to occupational heath legislations and lead controls for paint and gasoline, is extremely uncommon today (71).

Lead Toxicity in Children

Young children are more at risk from lead for a number of reasons:

1. The likelihood and level of exposure are greater (see 2.3 Exposure Routes, below)
2. The level of gastro-intestinal absorption is greater in children
3. Children have a increased soft tissue lead burden because their smaller skeletons store less lead
4. Development of organs and systems is incomplete, making them less able to eliminate lead
5. Children have lower thresholds for the haematological and neurological effects of lead.

Because the organs, neurological, immune, and hematological systems of a child under age of six are still developing, the effects of lead exposure are potentially much more significant and harmful in fetuses, infants, and young children. The neurological effects in children arising from lead exposure have been intensively studied. Recent research indicates that even very low blood lead levels may be associated with adverse effects on children's intellectual development and behaviour (8, 11, 29, 73). For this reason, in 1991 the U.S. Centers for Disease Control lowered their blood lead intervention level for children from 25 ug/dL to 10 ug/dL. (15). In 1994, following the recommendation of the Federal-Provincial Committee on Environmental and Occupational Health (28), Health Canada followed suit.

Other possible neurotoxic effects of lead in children include short-term memory loss, reading and spelling difficulties, impaired visual-motor function, poor perceptual integration, and impaired reaction time. The CDC document "Preventing Lead Poisoning in Young Children" (15) concludes that other adverse effects, such as decreased stature or growth, decreased hearing acuity and a decreased ability to maintain a steady posture may occur at relatively low blood lead levels. Low-level lead poisoning in children produces no specific symptoms and the chances of diagnosis and treatment are correspondingly reduced.

2.3 Exposure Routes

Lead may enter the body through ingestion, inhalation, dermal contact, or to the fetus via the placenta. In the Canadian general population the main exposure routes are the gastro-intestinal tract and respiration. Lead uptake by the fetus begins as early as the twelfth week and continues throughout development (36). The most common route of entry is ingestion, except in industrial environments where it is possible that inhalation plays a larger role (85). Dermal absorption of lead in the general population is rare, and generally results from exposure to organic lead compounds such as the gasoline additive tetraethyl lead, use of which has been severely curtailed in Canada by the Gasoline Regulations under the Canadian Environmental Protection Act.

Until the 1980's the two main sources of lead in the Canadian environment were house paints and emissions from leaded gasoline. In 1983 Canada initiated a phase-out of leaded gasoline and in 1990 the Gasoline Regulation under the Canadian Environmental Protection Act limited the use of leaded gasoline to competition vehicles, aircraft, farming equipment, boats and trucks of specific size. Lead concentration in urban air decreased from about 0.55 micrograms per cubic metre in 1975 to less than 0.05 in 1990, a drop of more than 90 percent (75). Under Health Canada's Hazardous Products Act the Liquid Coating Materials Regulations were enacted in 1976 to restrict the lead content of paints and other liquid coatings on furniture, household products, children's products, exterior and interior surfaces of any building frequented by children to 0.5% by weight. To reflect current scientific and medical knowledge, amendments to these Regulations which reduce the lead content of paints and other liquid coatings for these uses from 0.5% to 0.06 % by weight are currently being prepared.

Before the late 1980's lead was widely used in soldering food can side seams. A voluntary compliance program by Canadian canners has virtually eliminated the use of lead in food cans - nearly all food can side seams in Canada today are welded. Other major sources of lead exposure, such as ceramic glazes, drinking water distribution systems, cosmetics, and emissions from primary and secondary lead industries have been controlled through regulatory intervention and improved industry quality assurance programs.

Today lead exposure in the Canadian population occurs mainly through handling of consumer products containing lead, through certain home-based occupations and hobbies, and through exposure to indoor leaded dust. Because of lead's many uses, it is not possible to list all consumer products which may potentially contain lead. Products in which lead may be used include paints, pigments, frits, and other artists' supplies, lead crystal, protective/ decorative coatings on a wide variety of products, jewellery, decorative figurines, fastenings and trim on clothing, lead shot, fishing sinkers and jigs, lead came used in panel and stained glass windows and doors, batteries, and lead vent and roof flashings (40,44,45, 47,48, 79,80,108). Activities which may expose both adults and children to lead-containing products and to lead-contaminated dust include pottery-making, where lead glazing or lead pigments may be used, manufacture of stained glass items, which may produce fumes from the soldering of lead came and dust from sanding of leaded glass, and casting of fishing sinkers, lead shot or diving weights, which may produce fumes from melting lead (30,41).

Not only are the effects of lead toxicity more severe in young children, but they are also at greater risk of exposure to lead in consumer products because of their normal tendency to mouth or chew objects with which they come into contact. In addition, many children between one and six years also exhibit pica, an eating disorder described as a tendency to mouth or attempt to consume non-food objects such as paint chips, furniture, or toys.

Household dust and soil are significant sources of lead exposures for small children (25,93). The FDA estimated in 1990 that a two year old child received 16% of his or her total lead from food, 1% from soil and 75% from dust (102). Young children are most at risk from lead-containing dust because (i) their breathing zone is close to floor level (ii) their normal hand to mouth behaviour greatly increases the likelihood of ingesting dust, and (iii) they breathe in more air per unit body weight than do adults. A recent study has found the concentration of lead in house dust to be significantly greater than that of outdoor soil and dust from adjacent land (78). This was the case not only for pre-1970 homes, where the presence of lead-containing interior paints is to be expected, but also for recently built houses in areas with no industrial or commercial history - an indication that lead dust is being generated from within the home. Airborne lead dust settles onto food, water, clothing and other objects and may subsequently be transferred to the mouth. It has been estimated that the vast majority of dust particles that adhere to the hand are < 10 &µm in size (1) and therefore readily absorbed when ingested. Lanphear et al. (58) estimated that an increase in concentration of lead in dust from background to 200 µg/sq.ft (2.15 mg/m²) would produce 23.3% increase in the number of children with blood lead level > 10 micrograms per decilitre. An increase in soil lead concentration from background to 400 µg/g was estimated to produce an increase of 11.6% of children having a blood lead level > 10 micrograms per decilitre.

Evidence of pre-industrial exposure to lead suggests that human exposure to lead from natural sources is generally negligible (31). However, surveys of parent rock in Ontario and Quebec have found naturally occurring lead levels of up to 162 ppm, although the mean and medium values where much lower (55). While individuals living or working in these areas may occasionally be exposed through dust and soil to high natural levels of lead, the significance of natural sources on human exposure to lead is negligible compared to industrial sources.

2.4. Absorption, Distribution, and Storage of Lead in the Body

In adults having a normal diet, 3-15% of ingested lead is generally absorbed by the intestine and less than 5% of absorbed lead is retained in the body (37). Pregnant women absorb greater levels of ingested lead, approximating absorption levels in children. Depending on such factors as particle size, solubility, and density, and the individual's ventilation rate, approximately 30% to 50% of the airborne lead particulates inhaled by an adult are retained, of which nearly all are absorbed (68,101). The EPA (67) and Cal/OSHA (12) estimate that 80% of the lead fumes and soluble lead dusts inhaled into the lungs are absorbed into the body.

Regardless of the route of entry into the body, lead is absorbed directly through the blood into soft tissue, including the kidney, liver, and brain. Distribution of lead in the soft organs is preferentially in the liver, followed by the kidneys, pancreas and lungs. Other than the intestine, the kidney is the major organ for lead excretion. A very high proportion of absorbed lead is transferred to bone, along with other minerals such as calcium, where it accumulates over time and remains for long periods. In adults, lead is partitioned between the skeleton and the soft tissues in a ratio of approximately 95% bone and 5% soft tissue (95). The half-life, or time required for the body to excrete half its accumulated lead, is about 25 years. Therefore, high lead concentrations can be maintained within the body for years after exposure to lead has ceased (6). The total amount of lead stored or accumulated in the body is the body burden.

Lead in the bone may contribute as much as 50% to total blood lead, but the relative effect of endogenous and exogenous lead sources on blood lead depends greatly on the amount of lead that has been accumulated in the skeleton over time. Because of lead's 25-year half-life, an individual may be at risk for release of stored lead into the bloodstream throughout a lifetime. During periods of physiological stress, the minerals stored in bones, including lead, can be mobilized back into the bloodstream, resulting in increased blood lead levels. In women, lead is released from the bone in significant amounts during pregnancy and lactation as the calcium is mobilized. Osteoporosis, common in the elderly, especially elderly women, causes deterioration of the bone matrix and thus increases the rate of release of bone lead. In one report it was estimated that the total body burden of lead in 60 - 70 year old men may exceed 200 mg (85). In young children lead absorption and retention levels are thought to be much greater than in adults, but many uncertainties remain because of limited data. Fetuses and young children, especially those under the age of six, may be particularly susceptible (64). Children aged 2 weeks to 8 years absorb roughly 40 to 50% of ingested lead (4,108). One study found an infant's average net lead absorption to be 41.5% with a net retention of 31.8% when kept on a regular diet (65). The greater absorption and retention capacity found in young children has been linked to a higher metabolic rate and preferential absorption of calcium. The proportion of lead stored in soft tissues is also greater in children, because of the lesser storage capacity of their smaller skeletons. Newborns are especially affected by the toxicity of lead because of their high lead absorption rate and because their livers, which remove lead from blood, are not fully developed. (Lead is excreted into the bile in a concentration 100 times greater than the blood lead concentration.) These two factors produce an elevated blood lead concentration which increases the risk of neurological and other damage. Additionally, lead retention time in the child is protracted, thereby exacerbating the damage to the developing nervous system.