Human Lead Exposure Research Articles

Behavioral toxicology and risk assessment

In order to establish safe exposure levels to toxic chemicals, risk assessment guidelines have been developed. These guidelines evaluate epidemiologic and animal research data on a particular chemical, as well as dose-response relationships, animal to human extrapolation and assessment of exposure levels of populations. Using the guidelines, risk characterization is established in order to determine a strategy for reducing undesirable risk to human populations. Using both human neonatal lead exposure data and results from rodent and primate studies, this review examines the possibility that behavioral measurements are sufficient to provide adequate risk assessment guidelines for lead intoxication of the developing organism. The overall trend in these data during the past 10 years has been to show that exposures to inorganic lead at levels previously considered safe have long-lasting significant alterations in behavioral measures, suggesting that central nervous system function has been altered irreversibly. The conclusion is drawn that behavioral toxicology can provide sensitive, quantitative and reliable data for risk assessment and that in the future these methodologies could be used to set exposure guidelines for other neurotoxic chemicals.

Partial Purification and Properties of Nicotinamide Adenine Dinucleotide Synthetase From Human Erythrocytes: Evidence That Enzyme Activity Is a Sensitive Indicator of Lead Exposure

We have examined properties of nicotinamide adenine dinucleotide (NAD) synthetase from human erythrocytes. The enzyme was found to be cold labile and extremely unstable in crude hemolysate, with complete loss of activity occurring after 24 hours at 4 degrees C. However, maintenance of crude hemolysate at 20 to 25 degrees C in the presence of EDTA and KCl increased NAD synthetase stability substantially (half-life = 10 days). Using these conditions, NAD synthetase was purified 3,100-fold with a 29% yield using DEAE-cellulose column chromatography, ammonium sulfate fractionation, and dialysis. The apparent Michaelis-Menten constants for nicotinic acid adenine dinucleotide (NAAD), adenosine triphosphate, Mg2+, glutamine, and K+ were 0.108, 0.154, 1.36, 2.17, and 8.32 mmol/L, respectively. The pH optimum ranged between 6.8 and 7.4, and the molecular weight was estimated to be 483 +/- 5 Kd. The enzyme was markedly inhibited by Pb2+ and Zn2+, with concentrations necessary for 50% inhibition of activity of 1.3 and 2.0 mumol/L, respectively. The incubation of intact red blood cells with lead followed by rigorous washing to remove lead abolished nearly all NAD synthetase activity. In contrast, glucose-6-phosphate dehydrogenase activity, which is not sensitive to lead, was unaffected, whereas pyrimidine 5'-nucleotidase activity, which is sensitive to lead, was decreased 30% to 50% under these conditions. More importantly, patients with lead overburden (34 to 72 micrograms Pb2+/dL blood) all had markedly decreased NAD synthetase activity. These data together with other results suggest that erythrocyte NAD synthetase activity is a sensitive indicator of lead exposure in humans.

Partial purification and properties of nicotinamide adenine dinucleotide synthetase from human erythrocytes: evidence that enzyme activity is a sensitive indicator of lead exposure

We have examined properties of nicotinamide adenine dinucleotide (NAD) synthetase from human erythrocytes. The enzyme was found to be cold labile and extremely unstable in crude hemolysate, with complete loss of activity occurring after 24 hours at 4 degrees C. However, maintenance of crude hemolysate at 20 to 25 degrees C in the presence of EDTA and KCl increased NAD synthetase stability substantially (half- life = 10 days). Using these conditions, NAD synthetase was purified 3,100-fold with a 29% yield using DEAE-cellulose column chromatography, ammonium sulfate fractionation, and dialysis. The apparent Michaelis- Menten constants for nicotinic acid adenine dinucleotide (NAAD), adenosine triphosphate, Mg2+, glutamine, and K+ were 0.108, 0.154, 1.36, 2.17, and 8.32 mmol/L, respectively. The pH optimum ranged between 6.8 and 7.4, and the molecular weight was estimated to be 483 +/- 5 Kd. The enzyme was markedly inhibited by Pb2+ and Zn2+, with concentrations necessary for 50% inhibition of activity of 1.3 and 2.0 mumol/L, respectively. The incubation of intact red blood cells with lead followed by rigorous washing to remove lead abolished nearly all NAD synthetase activity. In contrast, glucose-6-phosphate dehydrogenase activity, which is not sensitive to lead, was unaffected, whereas pyrimidine 5′-nucleotidase activity, which is sensitive to lead, was decreased 30% to 50% under these conditions. More importantly, patients with lead overburden (34 to 72 micrograms Pb2+/dL blood) all had markedly decreased NAD synthetase activity. These data together with other results suggest that erythrocyte NAD synthetase activity is a sensitive indicator of lead exposure in humans.

Lead levels in ancient and contemporary Japanese bones

During the past few centuries, lead production, consumption and emissions, to our total environment have increased remarkably. We have determined the concentrations of lead in 41 well-preserved ancient and 11 contemporary rib bones of a mature age (40-60 y), with a view of historically evaluating lead exposure in humans. The oldest Japanese bones (1000-300 B.C.) were found to contain a mean of 0.58 microgram Pb/g dry wt and a mean molar ratio of lead to calcium of 0.6 x 10(-6), compared with 4.7-5.2 x 10(-6) in the bones of the Edo era (1600-1867 A.D.) and contemporary residents in Japan. The mean molar ratios of female bones were always higher than those of male bones for each era. From this fact we may assume that facial cosmetics were one of the main routes of lead exposure among the ancient Japanese, especially those who lived during the Edo era.

Traffic as a source of lead exposure in childhood

Experimental and observational data has long implicated automobile exhaust from leaded petrol as a major source of human lead exposure. The present study evaluates the association of individual traffic exposure with individual lead absorption. A case-referent study was carried out on 1302 out of 2412 children in the municipality of Aarhus - Denmark. Shed deciduous teeth were matched for sex and socioeconomic status. Individual lead sources were assessed by an interview. Information on former addresses and the data of address change was obtained as was information on the daily number of cars driving on all roads of the city. A traffic index was constructed describing the traffic density at the home. An association between high lead and high traffic density was found in the children at the age of 6 months to 2 years. This relationship was of a dose-response nature. The association was not accounted for by other possible major sources.

Nail Lead Concentration as an Index of Environmental Lead Exposure

AbstractA method for screening human lead exposure was validated by using fingernail lead concentrations in comparison with blood lead concentrations of 40 children and 44 adults. A multiple regression analysis performed in the above sets of measurements revealed two statistical equations with which one could determine the blood lead concentrations from the corresponding nail lead concentrations in both groups.

Lead Absorption in Children: Management, Clinical and Environmental Aspects

The past 15 years has witnessed a great expansion in the understanding of lead exposure in humans. This progress has taken place on a number of fronts, only some of which are strictly scientific, fulfilling the statement made by Rene Dubos a number of years ago that the subject of lead exposure offers a piece of action to practically every field of human endeavor. An example of this is the recent action taken by the Environmental Protection Agency to reduce further the permissible lead content in gasoline, surely as important a step as any current scientific discovery in the field. Amelioration of lead exposure will never occur without the broad cooperation of not only bench scientists, behavioralists, and clinical people, but also public health, legal, legislative, and governmental persons sharing common concerns. The subject matter of this volume represents just this kind of cooperative effort, as one can easily see

Dependence of Apparent Blood Lead Half-Life on the Length of Previous Lead Exposure in Humans

Dependence of Apparent Blood Lead Half-Life on the Length of Previous Lead Exposure in Humans

Dependence of apparent blood lead half-life on the length of previous lead exposure in humans

The expected relationship between the apparent half-life of blood lead (PbB) and the length of previous exposure is compared with the observed relationship in a group of workers on strike from a primary smelter where they had been employed for from a few months to ten years. Within this group, the apparent PbB half-life was positively correlated both with pre-strike PbB and with length of exposure to lead. It is likely that the dependence of apparent half-life on pre-strike PbB is primarily a reflection of interindividual differences in lead kinetics in these men. The direct dependence of apparent half-life on duration of lead exposure is consistent with published data from former lead workers and from human subjects experimentally exposed to lead.

Lead, zinc, and copper levels in intraocular brain tissue grafts, brain, and blood of lead-exposed rats

Adult female Sprague-Dawley rats were exposed to various concentrations of lead acetate for different lengths of time. Six weeks exposure to lead acetate at concentrations of 0, 0.125, 0.25, 0.5, 1, and 2% in the drinking water, gave rise to brain and blood lead levels that were highly correlated with the lead concentration in the drinking water. When animals were exposed to 1% lead acetate for different lengths of time, an apparent delay in the rate of lead transport into the brain was seen during the first day. However, if animals were exposed for longer time periods, brain lead levels increased faster than did the blood levels. Pieces of fetal cortex cerebri were grafted to the anterior eye chamber of host animals exposed to either 1% lead acetate or to sodium acetate. Six weeks after grafting, the lead concentration in the lead-exposed grafts were 31.6 mg/kg dry wt, as compared to 6.4 mg/kg dry wt in sodium acetate control grafts. However, grafts from both groups had lead levels that were approximately five times higher than in cerebral cortex “punches” from corresponding areas of the host brains. Furthermore, zinc and copper levels were also higher in the grafts as compared to punches of in situ cortex. Taken together with previous reports on animal and human lead exposure, these data indicate that oral lead intake in adult rats bearing intraocular brain grafts yields blood and brain levels which are physiologically relevant to problems of clinical lead toxicity.

Electric kettles as a source of human lead exposure.

Five hundred and seventy-four households in Ottawa were surveyed to evaluate water boiled in electric kettles as a source of lead exposure. Samples of boiled water exceeded the World Health Organization mandatory limit for drinking water (50 microgram/l) in 42.5% of the households. Excessive lead concentrations were observed in 62.8% of water samples from kettles more than 5 years old. Multiple regression analysis indicated that age, sex, and cigarette smoking habits, but not lead concentration in boiled water, nor weekly consumption of boiled water were significantly associated with blood-lead concentration. Lead exposure from electric kettles may be a significant problem only in infants receiving formula prepared with boiled water.

δ-Aminolevulinic Acid Dehydratase—A Sensitive Indicator of Lead Exposure in Japanese Quail

Red blood cell δ-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 μg. 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 < 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 < 0.001). RBC-ALAD activity expressed as the log. base 10 showed significant (P < 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.

Erythrocyte porphobilinogen synthase (delta-aminolaevulinate dehydratase) activity: a reliable and quantitative indicator of lead exposure in humans.

We assessed optimal conditions for assay of porphobillinogen synthase (EC 4.2.1.24) activity in human blood containing abnormally high concentrations of lead. Zn2+and -SH, both required for complete activation of the enzyme, had additive effects. Using a modified method based on these studies, we found blood lead concentration to be strictly proportional to ln(activated/nonactivated) enzyme activity. One brand of commercially available "lead-free" tubes contained a substance that interfered with this relationship. In vitro studies, with the modified assay, showed ALAD to be activated by low concentrations but inactivated by high concentrations of Hg2+, Cd2+, and ethylenediaminetetraacetate. We fouund no genetically influenced differences among unexposed individuals when in(activated/nonactivated) enzyme activities were compared. The technique is suitable for use in screening for lead poisoning in humans.