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Levels of lead ingestion and inhalation producing increased body burden of lead and clinical toxicity in adults and children are compared with usual levels of exposure. The magnitude of lead exposure from air, water, and food is estimated. Sources of high level exposure to lead are described; urban street dirt, house dust, and paint are particularly common sources of high concentrations of lead. The bioavailability of different lead compounds is reviewed as well as factors affecting susceptibility to lead.

Nutritional factors such as deficiencies of calcium, iron, and protein alter susceptibility to the toxic effects of lead. While the suggestion has been made that vitamins may also influence lead toxicity, possible interactions have not been well documented. The present studies were performed to determine if a dietary deficiency of folic acid enhances the susceptibility to rats of the toxic effects of lead acetate. Lead exposure during the development of folate deficiency resulted in alterations in two of the parameters diagnostic of the individual conditions. Decreases in erythrocyte mean corpuscular volume (MCV) occur during lead poisoning, while increases occur during the development of folate deficiency. In the present study, significant reductions in MCV were observed in both the control + lead and in the low folate + lead groups. The increased MCV characteristic of folate deficiency was prevented by the concomitant lead exposure. Elevations in free erythrocyte protoporphyrin (FEP) levels are characteristic of lead intoxication; in contrast, FEP levels decline during folate deficiency. In the present study, FEP levels were significantly elevated only in the control + lead group. Values in the low folate + lead group were intermediate between those of the control and the control + lead groups, but did not differ significantly from those in the low folate group. The expected lead-induced elevation in FEP levels was diminished by the reduced erythropoiesis characteristic of folate deficiency.

A rapid bioassay of lead was established in young japanese quail. Each group of 10 day-old birds received deionized water and a purified diet ad libitum for 2 wk. The diet contained 0.2 microgram lead/g. Lead acetate was added to give 14.8, 34.4, 51.2, 74.4, 234, 563, or 1223 microgram total lead/g by analysis. The duodenum, kidneys, liver and tibias were assayed for lead. Consumption of a diet containing either 563 or 1223 ppm lead caused a decrease (P less than or equal to 0.05) in body weight after 1 wk and an increase in free erythrocyte protoporphyrin after 2wk. Inhibition of red blood cell delta-aminolevulinic acid dehydratase (RBC-ALAD) activity occurred in birds consuming as little as 14.8 ppm lead. Packed cell volumes and hemoglobin concentrations were not affected by the dietary treatments. Lead concentrations in tissues from birds fed the lowest level of added lead were greater than those found in the corresponding tissues of control birds. The concentration of lead in the tibia showed the most distinguishable group means and the most nearly linear response; the highest slope was between 14.8 and 110 ppm dietary lead, using log-log transformations. The rapid bioassay is suitable for investigating high lead foods.

Red blood cell delta-aminolevulinic acid dehydratase (RBC-ALAD) activity has proven to be a sensitive indicator of lead exposure in humans. The depressed enzyme activity and its negative correlation to blood lead concentrations are well-known effects of lead exposure in man. The sensitivity of RBC-ALAD activity in young Japanese quail exposed to low levels of lead as lead acetate was investigated. Two groups of nine birds each were fed purified diets containing either no added lead or 25 micrograms of lead per g. of diet. After 2 weeks, blood samples for hematocrit, hemoglobin, and enzyme determinations and renal, hepatic, duodenal, and tibial tissues were collected. There were no significant differences between controls and lead-fed birds in body, kidney, duodenal, and tibial weights, or in hematocrit and hemoglobin concentrations. However, the renal, hepatic, duodenal, and tibial lead concentrations were significantly (P less than 0.001) greater in the lead-treated birds. The activity of RBC-ALAD in the group fed lead was 45% of that in the control group; these values were significantly different (P less than 0.001). RBC-ALAD activity expressed as the log. base 10 showed significant (P less than 0.02) negative correlation with both hepatic and tibial lead. The study demonstrates that the activity of RBC-ALAD in the Japanese quail is a very sensitive indicator of lead exposure.

Whether, and to what degree, dietary calcium is inversely associated with blood lead levels was examined in 2,926 black and white children, 1 to 11 years of age, from the Second National Health and Nutrition Examination Survey (NHANES II). Blood lead levels were significantly higher in black than in white children, whereas white children had significantly higher dietary calcium intake (P less than .0001). Using covariance analysis and multiple regression analysis, determinants of blood lead levels were assessed as follows. The dependent variable was log10 lead, with independent variables age, sex, race, height, Quetelet index, dietary intake of calcium, phosphorous, fat, carbohydrate, and calories, community size index, poverty index ratio, geographic region, urbanization index, and all two-way interactions of the preceding. In the multiple regression analysis, the following independent variables were significant, P less than .05. Race (black) and sex (male) were positively associated with blood lead level (P less than .0001 for both). The lower the family income and the more urban the family residence, the higher were the blood lead levels (P less than .0001, less than .008, respectively). A significant independent inverse association of blood lead levels with year of examination was noted, reflecting a downward secular trend in blood lead levels. Height was inversely associated with blood lead level (P less than .0001). Dietary calcium intake was also inversely associated with blood lead level (P = .028). Dietary intake of phosphorous, fat, carbohydrate, and total calories were not significantly associated with blood lead levels. The most direct strategy for prevention of childhood lead poisoning involves primary prevention to reduce exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans are exposed to a number of toxic elements in the environment; however, most experiments with laboratory animals investigate only one toxic element. To determine if concomitant exposure to lead (Pb), cadmium (Cd), and/or arsenic (As) modified the changes produced by any one metal in various parameters of toxicity, 168 male, Sprague-Dawley, young adult rats were fed nutritionally adequate diets to which had been added 0 or 200 ppm Pb as Pb acetate, or 50 ppm Cd as Cd chloride, or 50 ppm As as sodium arsenate or arsanilic acid in a factorial design for a period of 10 weeks. At these concentrations, Cd and As reduced weight gain even when differences in food intake were taken into account; administration of both Cd and As depressed weight gain more than did either metal alone. Pb did not adversely affect food consumption or weight gain. Increased numbers of red blood cells (RBCs) were observed following administration of Pb, Cd, or As; usually more cells were observed when two or three metals were administered, compared to individual metals. Despite increasing numbers of circulating RBCs, hemoglobin and hematocrit were reduced, especially with the Pb-Cd combination and the Cd-arsanilic acid combination. Specific effects of Pb on heme synthesis were observed, including increased urinary excretion of delta-aminolevulinic acid; this increase was reduced by the presence of dietary cadmium. Analyses of blood showed values for the laboratory rat within normal ranges for blood urea nitrogen, creatinine, cholesterol, calcium, albumin, total protein, and bilirubin. Uric acid was increased by Pb, with little modification by dietary Cd or As content. Serum glutamate-oxalate transaminase activity was reduced by As. Serum alkaline phosphatase was greatly reduced by either As or Cd but not Pb. Combinations of As and Cd did not further reduce the activity of this enzyme. Kidney weight and kidney weight/body weight ratios were increased by Pb alone, with no effects of Cd or As alone or as interactions. Liver weight/body weight ratios were reduced in animals fed 50 ppm dietary Cd. Kidney histology shows predominantly Pb effects, namely, intranuclear inclusion bodies and cloudy swelling. Ultrastructural evaluation of kidneys from Pb-treated animals disclosed nuclear inclusion bodies of the usual morphology and mitochondrial swelling. Concurrent administration of Cd greatly minimized Pb effects on the kidney under conditions of this experiment. Liver histology suggests an increased rate of cell turnover with either As compound, but few specific changes.

Nutritional status can substantially modify the toxicity of environmental pollutants. Investigations with experimental animals and epidemiological observations on humans have established the role of nutrition in altering susceptibility to a variety of pollutants including pesticides and heavy metals. The degree of nutritional deficiency that alters susceptibility need not be severe. Frequently only biochemical indications of nutritional deficiency can be associated with changes in the dose-response of an animal or person to a toxic compound.

Data from the second National Health Nutrition Examination Survey showed that 22 per cent of persons six months through 75 years old had blood lead levels under 10 micrograms per deciliter; 1.9 per cent had elevated levels (greater than or equal to 30 micrograms per deciliter [greater than or equal to 1.45 mumol per liter]). Among children six months through five years old the prevalence of elevated levels was significantly higher (4 per cent) than previously predicted on the basis of fewer data. The prevalence of elevated lead levels was 12.2 per cent in black children and 2.0 per cent in white children. Mean levels of blood lead were higher in blacks than white among children and adults, among young children living in urban and rural areas, and among members of low-income, moderate-income, and higher-income families. These racial contrasts may reflect different lead exposure or absorption (or both). Young children from families (both white and black) whose incomes were under $6,000 had a significantly higher prevalence of elevated lead levels than those from households with incomes of $6,000 or more.

Major metabolic effects of lead are briefly reviewed and available data on quantitative relationships between lead ingestion and development of toxicity in adults and children are discussed. Levels of lead ingestion producing clinical toxicity in adults are compared with normal levels of exposure. For children, comparison of levels of lead ingestion and quantities of lead producing toxic effects is not currently possible, as information on levels of lead producing clinical toxicity appears to be highly variable on the basis of the small amount of data available. However, recommendations on tolerable levels of lead exposure for childrne are proposed, based on estimates of lead exposure for children having normal and elevated body burdens of lead.

Two methods for the determination of lead absorption have been developed using the rat as the test animal. One is an everted intestinal sac method in which the time course of 210Pb transport across intestinal wall can be followed in vitro; and the other, 210Pb absorption from the intestine following gastric intubation can be followed in vivo. By using these techniques it can be clearly demonstrated that vitamin D markedly enhances lead absorption. Both techniques provide evidence that the distal small intestine is the major site of lead absorption and the site of greatest vitamin D stimulation. Lead acetate is apparently absorbed to the extent of 45% as it passes through the small intestine at a concentration of 0.01 mM.

Both iron status and body burden of lead influence heme biosynthesis. Measurement of protoporphyrin IX in the circulating erythrocyte (EP) has been used to index the extent of lead exposure and iron deficiency. The association of iron status and blood lead level with the level of EP in whole blood for persons ages 6 months through 74 years in the general U.S. population has been investigated by using data obtained in the second National Health and Nutrition Examination Survey (NHANES II). Iron status was defined as a function of percentage transferrin saturation (%TS) and total iron-binding capacity (TIBC). Both low iron status (%TS less than or equal to 16.0 or TIBC greater than or equal to 450 micrograms/dl serum) and elevated blood lead levels (greater than or equal to 30 micrograms/dl) were associated with increased EP concentrations. The analysis of the proportions of persons in the U.S. population with EP levels above the 95th percentile (30 micrograms EP/dl of whole blood in the NHANES II data) support the concern that iron status has considerable influence on interpretation of EP levels recommended for use in screening programs aimed at identifying children with lead toxicity. With screening techniques based on EP only, currently used in various public health programs, a considerable number of children with blood lead levels of greater than or equal to 30 and less than or equal to 50 micrograms/dl are not referred for further diagnostic evaluation.

The Food and Drug Administration has a continuing program of monitoring foods for their content of lead, cadmium, mercury, zinc, arsenic, and selenium to determine trends of increasing or decreasing levels. The monitoring protocol is that of the Total Diet Study, in which "market baskets" of typical foods and beverages consumed by 15- to 20-year-old American males are collected in various geographical locations at regular intervals during the year, divided into food classes, composited, and analyzed. Cadmium has the most widespread distribution of the six heavy metals and mercury the most limited. The analytical values for lead may be underestimated because of limitations of the methodology; these do not apply to the other five elements. A tabulation by year shows that the levels of these elements in foods do not vary significantly from one year to the next. Average intakes of lead, cadmium, and mercury are below the WHO/FAO tolerable intakes for adults; such tolerable intakes have not been established for arsenic and selenium. Increases in concentrations of these elements in foods would be considered undesirable, however.

The relative toxicity of low doses of lead acetate provided steadily in drinking water or by mouth once per week was studied in weanling and adult rats. Free erythrocyte protoporphyrin and urinary delta-aminolevulinic acid levels were measured, as well as lead levels in blood and kidney. The accumulation of lead in brain tissue and in bone (femur) was measured to determine the effect of age and schedule of administration on tissue distribution and retention of lead. Total intakes of lead during the 60-week experimental period were: weanling and adult rats exposed to drinking water supplemented with 200 microgram of lead acetate/ml: 127 +/- 10 mg and 160 +/- 16 mg, respectively; weanling and adult rats dosed with lead acetate orally once per week: 132 mg and 161 mg, respectively. Increased toxic effects of lead in the weanling animals were apparent in most of the parameters measured (urinary delta-aminolevulinic acid and blood, brain, femur and kidney lead levels). This pattern was observed in weanling rats exposed to lead steadily through drinking water or dosed orally with an equivalent quantity of lead once per week. Lead levels in blood were highly correlated with the accumulation of lead in brain, femur, and kidney tissue in both groups of weanling rats. In adult rats, significant correlations between blood lead and kidney lead and between blood lead and femur lead were found only in the rats receiving lead steadily in drinking water.