The Risk Assessment Information System

Toxicity Profiles

Condensed Toxicity Summary for LEAD

NOTE: Although the toxicity values presented in these toxicity profiles were correct at the time they were produced, these values are subject to change. Users should always refer to the Toxicity Value Database for the current toxicity values.

December 1994

Prepared by Kowetha A. Davidson, Ph.D., Chemical Hazard Evaluation and Communication Program, Biomedical and Environmental Information Analysis Section, Health Sciences Research Division, *, Oak Ridge, Tennessee.


*Managed by Martin Marietta Energy Systems, Inc., for the U.S. Department of Energy under contract No. DE-AC05-84OR21400.

Lead occurs naturally as a sulfide in galena. It is a soft, bluish-white, silvery gray, malleable metal with a melting point of 327.5C. Elemental lead reacts with hot boiling acids and is attacked by pure water. The solubility of lead salts in water varies from insoluble to soluble depending on the type of salt (IARC, 1980; Goyer, 1988; Budavari et al., 1989).

Lead is a natural element that is persistent in water and soil. Most of the lead in environmental media is of anthropogenic sources. The mean concentration is 3.9 ug/L in surface water and 0.005 ug/L in sea water. River sediments contain about 20,000 ug/g and coastal sediments about 100,000 ug/g. Soil content varies with the location, ranging up to 30 ug/g in rural areas, 3000 ug/g in urban areas, and 20,000 ug/g near point sources. Human exposure occurs primarily through diet, air, drinking water, and ingestion of dirt and paint chips (EPA, 1989; ATSDR, 1993).

The efficiency of lead absorption depends on the route of exposure, age, and nutritional status. Adult humans absorb about 10-15% of ingested lead, whereas children may absorb up to 50%, depending on whether lead is in the diet, dirt, or paint chips. More than 90% of lead particles deposited in the respiratory tract are absorbed into systemic circulation. Inorganic lead is not efficiently absorbed through the skin; consequently, this route does not contribute considerably to the total body lead burden (EPA, 1986a).

Lead absorbed into the body is distributed to three major compartments: blood, soft tissue, and bone. The largest compartment is the bone, which contains about 95% of the total body lead burden in adults and about 73% in children. The half-life of bone lead is more than 20 years. The concentration of blood lead changes rapidly with exposure, and its half-life of only 25-28 days is considerably shorter than that of bone lead. Blood lead is in equilibrium with lead in bone and soft tissue. The soft tissues that take up lead are liver, kidneys, brain, and muscle. Lead is not metabolized in the body, but it may be conjugated with glutathione and excreted primarily in the urine (EPA, 1986a,c; ATSDR, 1993). Exposure to lead is evidenced by elevated blood lead levels.

The systemic toxic effects of lead in humans have been well-documented by the EPA (EPA, 1986a-e, 1989a, 1990) and ATSDR (1993), who extensively reviewed and evaluated data reported in the literature up to 1991. The evidence shows that lead is a multitargeted toxicant, causing effects in the gastrointestinal tract, hematopoietic system, cardiovascular system, central and peripheral nervous systems, kidneys, immune system, and reproductive system. Overt symptoms of subencephalopathic central nervous system (CNS) effects and peripheral nerve damage occur at blood lead levels of 40-60 ug/dL, and nonovert symptoms, such as peripheral nerve dysfunction, occur at levels of 30-50 ug/dL in adults; no clear threshold is evident. Cognitive and neuropsychological deficits are not usually the focus of studies in adults, but there is some evidence of neuropsychological impairment (Ehle and McKee, 1990) and cognitive deficits in lead workers with blood levels of 41-80 ug/dL (Stollery et al., 1993).

Although similar effects occur in adults and children, children are more sensitive to lead exposure than are adults. Irreversible brain damage occurs at blood lead levels greater than or equal to 100 ug/dL in adults and at 80-100 ug/dL in children; death can occur at the same blood levels in children. Children who survive these high levels of exposure suffer permanent severe mental retardation.

As discussed previously, neuropsychological impairment and cognitive (IQ) deficits are sensitive indicators of lead exposure; both neuropsychological impairment and IQ deficits have been the subject of cross-sectional and longitudinal studies in children. One of the early studies reported IQ score deficits of four points at blood lead levels of 30-50 ug/dL and one to two points at levels of 15-30 ug/dL among 75 black children of low socioeconomic status (Schroeder and Hawk, 1986).

Very detailed longitudinal studies have been conducted on children (starting at the time of birth) living in Port Pirie, Australia (Vimpani et al., 1985, 1989; McMichael et al., 1988; Wigg et al., 1988; Baghurst et al., 1992a,b), Cincinnati, Ohio (Dietrich et al., 1986, 1991, 1992, 1993), and Boston, Massachusetts (Bellinger et al., 1984, 1987, 1990, 1992; Stiles and Bellinger 1993). Various measures of cognitive performance have been assessed in these children. Studies of the Port Pirie children up to 7 years of age revealed IQ deficits in 2-year-old children of 1.6 points for each 10-ug/dL increase in blood lead, deficits of 7.2 points in 4-year-old children, and deficits of 4.4 to 5.3 points in 7-year-old children as blood lead increased from 10-30 ug/dL. No significant neurobehavioral deficits were noted for children, 5 years or younger, who lived in the Cincinnati, Ohio, area. In 6.5-year-old children, performance IQ was reduced by 7 points in children whose lifetime blood level exceeded 20 ug/dL.

Children living in the Boston, Massachusetts, area have been studied up to the age of 10 years. Cognitive performance scores were negatively correlated with blood lead in the younger children in the high lead group (greater than or equal to 10 ug/dL), and improvements were noted in some children at 57 months as their blood lead levels became lower. However, measures of IQ and academic performance in 10-year-old children showed a 5.8-point deficit in IQ and an 8.9-point deficit in academic performance as blood lead increased by 10 ug/dL within the range of 1-25 ug/dL. Because of the large database on subclinical neurotoxic effects of lead in children, only a few of the studies have been included. However, EPA (EPA, 1986a, 1990) concluded that there is no clear threshold for neurotoxic effects of lead in children.

In adults, the cardiovascular system is a very sensitive target for lead. Hypertension (elevated blood pressure) is linked to lead exposure in occupationally exposed subjects and in the general population. Three large population-based studies have been conducted to study the relationship between blood lead levels and high blood pressure. The British Regional Heart Study (BRHS) (Popcock et al., 1984), the NHANES II study (Harlan et al., 1985; Pirkle et al., 1985; Landis and Flegal, 1988; Schwartz, 1990; EPA, 1990), and Welsh Heart Programme (Ellwood et al., 1988a,b) comprise the major studies for the general population. The BRHS study showed that systolic pressure greater than 160 mm Hg and diastolic pressure greater than 100 mm Hg were associated with blood lead levels greater than 37 ug/dL (Popcock et al., 1984). An analysis of 9933 subjects in the NHANES study showed positive correlations between blood pressure and blood lead among 12-74-year-old males but not females (Harlan et al., 1985; Landis and Flegal et al., 1988), 40-59-year-old white males with blood levels ranging from 7-34 ug/dL (Pirkle et al., 1985), and males and females greater than 20 years old (Schwartz, 1991). In addition, left ventricular hypertrophy was also positively associated with blood lead (Schwartz, 1991). The Welsh study did not show an association among men and women with blood lead of 12.4 and 9.6 ug/dL, respectively (Ellwood et al., 1988a,b). Other smaller studies showed both positive and negative results. The EPA (EPA, 1990) concluded that increased blood pressure is positively correlated with blood lead levels in middle-aged men, possibly at concentrations as low as 7 ug/dL. In addition, the EPA estimated that systolic pressure is increased by 1.5-3.0 mm Hg in males and 1.0-2.0 mm Hg in females for every doubling of blood lead concentration.

The hematopoietic system is a target for lead as evidenced by frank anemia occurring at blood lead levels of 80 ug/dL in adults and 70 ug/dL in children. The anemia is due primarily to reduced heme synthesis, which is observed in adults having blood levels of 50 ug/dL and in children having blood levels of 40 ug/dL. Reduced heme synthesis is caused by inhibition of key enzymes involved in the synthesis of heme. Inhibition of erythrocyte -aminolevulinic acid dehydrase (ALAD) activity (catalyzes formation of porphobilinogen from -aminolevulinic acid) has been detected in adults and children having blood levels of less than 10 ug/dL. ALAD activity is the most sensitive measure of lead exposure, but erythrocyte zinc protoporphyrin is the most reliable indicator of lead exposure because it is a measure of the toxicologically active fraction of bone lead. The activity of another erythrocyte enzyme, pyrimidine-5-nucleotidase, is also inhibited by lead exposure. Inhibition has been observed at levels below 5 ug/dL; no clear threshold is evident.

Other organs or systems affected by exposure to lead are the kidneys, immune system, reproductive system, gastrointestinal tract, and liver. These effects usually occur at high blood levels, or the blood levels at which they occur have not been sufficiently documented.

The EPA has not developed an RfD for lead because it appears that lead is a nonthreshold toxicant, and it is not appropriate to develop RfDs for these types of toxicants. Instead the EPA has developed the Integrated Exposure Uptake Biokenetic Model to estimate the percentage of the population of children up to 6 years of age with blood lead levels above a critical value, 10 ug/dL. The model determines the contribution of lead intake from multimedia sources (diet, soil and dirt, air, and drinking water) on the concentration of lead in the blood. Site-specific concentrations of lead in various media are used when available; otherwise default values are assumed. The EPA has established a screening level of 400 ppm (ug/g) for lead in soil (EPA, 1994a).

Inorganic lead and lead compounds have been evaluated for carcinogenicity by the EPA (EPA, 1989, 1993). The data from human studies are inadequate for evaluating the potential carcinogenicity of lead. Data from animal studies, however, are sufficient based on numerous studies showing that lead induces renal tumors in experimental animals. A few studies have shown evidence for induction of tumors at other sites (cerebral gliomas; testicular, adrenal, prostate, pituitary, and thyroid tumors). A slope factor was not derived for inorganic lead or lead compounds. Retrieve Toxicity Profiles Formal Version

Last Updated 10/31/97

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