Lead exposure during infancy permanently increases lithium-induced polydipsia.

Lead (200 milligrams per kilogram) was administered daily by intubation to Long-Evans rats on days 3 through 30 of life. Thirty to 180 days after cessation of lead administration, the lead-treated rats were consistently more polydipsic after lithium administration (2 millimoles per kilogram per day) than were pair-treated controls. Lithium increased the plasma renin activity equally in both the lead treated and the control groups. These data are evidence that there may be permanent neural changes induced by postnatal exposure to lead that are manifested by pharmacological challenge with lithium.

Blood lead concentrations in a remote Himalayan population.

The lead content in the air at the foothills of the Himalayas in Nepal was found to be negligible. The concentration of lead in the blood of 103 children and adults living in this region was found to average 3.4 micrograms per deciliter, a level substantially lower than that found in industrialized populations.

Differential vulnerability of mixed and cutaneous nerves in lead neuropathy.

The prevalence of demyelinated fibers in mixed nerve (sciatic) and cutaneous nerve (sural) and the change in lead levels in various tissues over time were assessed in a model of lead neuropathy in the rat. Long-Evans rats were given drinking water containing 4% lead acetate and killed between one and 213 days of exposure. Lead levels in blood, brain, kidney, and femur increased over the 213-day period. Lead levels in sciatic nerve appeared to increase rapidly during the first few weeks of exposure and then decline to a lower plateau. The neuropathy was characterized by segmental demyelination and remyelination; neither axonal degeneration nor a microangiopathy was found. Sciatic nerve had a significantly greater prevalence of demyelinated fibers than sural nerve; the prevalence of demyelinated fibers was similar in proximal and distal sciatic nerve. The variable, brain-lead concentration times days on lead, which is an indicator of cumulative brain exposure, was the best predictor of the prevalence of demyelination. The differential involvement of sciatic and sural nerves in lead neuropathy may either indicate that Schwann cells myelinating different nerve-fiber populations have different susceptibilities to lead toxicity, or that lead preferentially enters sciatic nerve.

Uses and limits of empirical data in measuring and modeling human lead exposure.

This paper examines the uses and limits of empirical data in evaluating measurement and modeling approaches to human lead exposure. Empirical data from experiment or observation or both have been used in studies of lead exposure. For example, experimental studies have elucidated and quantified physiologic or biokinetic parameters of lead exposure under controlled conditions. Observation, i.e., epidemiology, has been widely applied to study population exposures to lead. There is growing interest in the use of lead exposure prediction models and their evaluation before use in risk assessment. Empirical studies of lead exposure must be fully understood, especially their limits, before they are applied as "standards" or reference information for evaluation of exposure models, especially the U.S. Environmental Protection Agency's lead biokinetic model that is a focus of this article. Empirical and modeled datasets for lead exposure may not agree due to a) problems with the observational data or b) problems with the model; caution should be exercised before either a model or observational data are rejected. There are at least three sources of discordance in cases where there is lack of agreement: a) empirical data are accurate but the model is flawed; b) the model is valid but reference empirical data are inaccurate; or c) neither empirical data nor model is accurate, and each is inaccurate in different ways. This paper evaluates some of the critical empirical input to biokinetic models, especially lead bioavailability.

Potential impact of acid precipitation on arsenic and selenium.

The potential impact of acidic precipitation on the environmental mobility of the metalloids arsenic (As) and selenium (Se) has not been given much attention and is poorly understood. As with other elements, the interest here is the potential effect of environmental acidification on environmental behavior in ways that are relevant to human exposure to these metalloids. Available information on acid precipitation and the environmental behavior of these metalloids do, however, permit some preliminary conclusions to be drawn. Both As and Se appear to be mobilized from household plumbing into tap water by the corrosive action of soft, mildly acidic water, while surface water catchment systems in areas impacted by acidic deposition may contain elevated soluble As levels. Acidification of aquatic ecosystems that are drinking water sources may pose the prospect of enhanced release of As from sediment to water as well as reduction in water levels of Se. Acidification of ground waters, where As appears to be especially mobile, is of particular concern in this regard. The potential impact of acidic deposition on As and Se in soils cannot readily be assessed with respect to human exposure, but it would appear that the behavior of these metalloids in poorly buffered, poorly immobilizing soils, e.g., sandy soils of low metal hydrous oxide content, would be most affected. The effect is opposite for the two elements; lowered pH would appear to enhance As mobility and to reduce Se availability. Altered acidity of both soil and aquatic systems poses a risk for altered biotransformation processes involving both As and Se, thereby affecting the relative amounts of different chemical forms varying in their toxicity to humans as well as influencing biogeochemical cycling.

Risk and revisionism in arsenic cancer risk assessment.

Oral exposures of nonoccupational populations to environmental inorganic arsenic are associated with skin and internal cancers as well as various noncarcinogenic effects. Cancer risk assessments have been based largely on epidemiological studies of a large population exposed to inorganic arsenic in well water in Taiwan. Criticisms and skepticism of the use of the Taiwanese data for estimating arsenic cancer risks outside of Taiwan, including potential use by the U.S. Environmental Protection Agency for regulatory purposes, have been expressed on various grounds. The nature and extent of such criticisms have sharpened with recent findings in the exposed Taiwanese of increased incidence of internal cancers (bladder, kidney, liver, and lung), in addition to already-observed skin cancer, coupled with a good likelihood that these findings will produce more stringent arsenic regulation in the United States and elsewhere. These criticisms collectively posit a revisionist view that: 1) cancer incidence among the Taiwanese was amplified by a number of host and environmental factors not applicable elsewhere, 2) the cancer dose-response curve may not be linear at the lower exposures elsewhere, and 3) there is a toxicokinetic and metabolic threshold to cancer risk that was exceeded by the Taiwanese. However, a number of the arguments against wide use of the Taiwanese data are flawed and subject to challenge. We explore some of these arguments and their critical evaluation, particularly as they concern certain exposure, metabolic, and nutritional determinants of the cancer risk of inorganic arsenic in the Taiwanese.

Methods for reducing lead exposure in young children and other risk groups: an integrated summary of a report to the U.S. Congress on childhood lead poisoning.

As part of a Congressionally mandated report on U.S. childhood lead poisoning prepared by the Federal government (U.S. Agency for Toxic Substances and Disease Registry [ATSDR]), the authors have analyzed the relative effectiveness of measures to reduce source-specific lead exposure of U.S. children. An integrated overview of this analysis is presented in this article. Two national actions, the Federally mandated phasedown of lead in gasoline by the U.S. Environmental Protection Agency and the voluntary phasedown of lead use in domestic food can production, are examples of centrally directed initiatives that have been relatively successful in limiting childhood lead exposure in the U.S. Efforts to abate lead-based paint exposure of children have largely failed. This is especially true for the nation's 21 million residential units with the highest lead content paint. Similarly, abatement of lead exposure from contaminated dusts and soils has generally been unsuccessful. Comprehensive measures to reduce lead exposure from drinking water in residences and public facilities, e.g., elementary schools, are only now being promulgated or implemented. The full extent of their effectiveness remains to be demonstrated. There are many miscellaneous but potentially severe exposure sources that are difficult to control but require attention, such as poorly glazed foodware and ethno-specific preparations.

Flameless atomic absorption (FAA) and gas-liquid chromatographic studies in arsenic bioanalysis.

Procedures for assessment of arsenic in soft tissue by use of flameless atomic absorption (FAA) and gas-liquid chromatography (GLC), have been evolved, with special emphasis on the analytical distinction among inorganic, monomethyl-, and dimethylarsenic in several oxidation states. The chemical bases for such speciation reside in several properties of the arsenicals under consideration: (1) pentavalent inorganic arsenic, methylarsonic, and cacodylic acid are not extracted from tissue matter made strongly acid with hydrochloric acid, while the corresponding trivalent forms (as halides) are extracted; (2) chloroform extracts of samples treated under reducing conditions (HCl-KI) retain organoarsenicals when these extracts are re-extracted with water, but do not when aqueous solutions of oxidants are employed; (3) reduced cacodylate (dimethylarsinous acid) is not detected in the graphite furnace of an FAA unit under conditions selected, while cacodylate can be so detected. For GLC studies, monomethyl- and dimethylarsenic are simultaneously measured as the diethyldithiocarbamate complexes with an instrument equipped for electron-capture detection and containing a glass column packed with silanized 5% OV-17 on Anakrom A.S.

Determination of numbers of lead-exposed U.S. children by areas of the United States: an integrated summary of a report to the U.S. Congress on childhood lead poisoning.

In response to Congressional mandate and under the aegis of the Federal Agency for Toxic Substances and Disease Registry (ATSDR), a comprehensive report to Congress on childhood lead poisoning in the United States was prepared. We have examined numbers of lead-exposed U.S. children by socioeconomic/demographic strata for children 0.5 to 5 years of age; by children in U.S. lead-screening programs; and by enumerations of children 0.5 to 5 years old in the oldest (i.e., highest paint lead and lead plumbing) housing. Using blood lead (PbB) prevalence projection modeling and data of the Second National Health and Nutrition Examination Surgery (NHANES II), it is estimated for 1984 that 2.4 million black and white children 0.5 to 5 years old in metropolitan U.S. had PbB levels greater than 15 micrograms/dL. For all races and the entire nation, we estimate 3 to 4 million children will have PbB levels greater than 15 micrograms/dL. Inner-city, low-income children have the highest prevalences of PbB levels above this criterion level, but sizable numbers of all strata of children have elevated PbB levels when considering both base populations and prevalences for the specific strata (total of 30 strata). Lead screening programs indicate much lower numbers of exposed children compared to NHANES II-based projections, for various reasons that allow programs to underestimate true prevalences. Analysis of 1980 U.S. Census Bureau housing data for 318 standard metropolitan statistical areas show that 4.4 million children 0.5 to 5 years old live in the oldest U.S. housing (pre-1950). Of these, most are actually in the more affluent socioeconomic strata.

Determination of numbers of lead-exposed women of childbearing age and pregnant women: an integrated summary of a report to the U.S. Congress on childhood lead poisoning.

In a Congressionally mandated study carried out under the aegis of the U.S. Agency for Toxic Substances and Disease Registry (ATSDR) and summarized in this article, the authors have provided estimates of the numbers of American women of childbearing age and the numbers of American pregnant women whose lead exposure is sufficiently elevated to pose an intrauterine toxicity risk. Exposures associated with such risk were defined as blood lead (PbB) levels greater than 10, greater than 15, greater than 20, and greater than 25 micrograms/dL. Using PbB prevalence projection techniques based on the Second National Health and Nutrition Examination Survey (NHANES II), we first generated projected 1984 prevalences of these PbB levels in white and black women of childbearing age, ages 15 to 19 and 20 to 44. White women in the two age bands had rates of PbBs greater than 10 micrograms/dL of 9.2 and 9.7%, respectively. For black women, the corresponding rates were 8.2 and 19.7%, respectively. Combining these rates with standard metropolitan statistical areas (SMSAs) based 1980 Census and other population enumerations show, for example, that 4.4 million U.S. women of childbearing age are estimated to have had PbBs greater than 10 micrograms/dL. Pregnant black and white women in U.S. SMSAs are approximately 9% of the U.S. black and white childbearing age total, i.e. 3.6 million out of a 41.3 million SMSA total. Of these, 403,200 pregnant women were estimated to have PbB levels greater than 10 micrograms/dL.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood-brain barrier dysfunction in acute lead encephalopathy: a reappraisal.

Acute lead encephalopathy was induced in adult guinea pigs by administering daily oral doses of lead carbonate. During the development of the encephalopathy, the structural and functional integrity of the blood-brain barrier was evaluated with electron microscopy and tracer probes. Blood, cerebral gray matter, liver, and kidney were analyzed for lead, calcium, and magnesium content. The animals regularly developed an encephalopathy after four doses of lead. There were no discernible pathomorphologic alterations in the cerebral capillaries or perivascular glial sheaths. Furthermore, no evidence of blood-brain barrier dysfunction was demonstrated with Evans blue-albumin complex or horseradish peroxidase. Blood-brain barrier permeability to radiolead was not increased in the intoxicated animals. During the development of the encephalopathy there was a progressive rise in the lead concentration in all tissues. Concurrently, there was a significant rise in brain calcium. These results suggest that the encephalopathic effects of lead may be mediated directly at the neuronal level.

Potential human health effects of acid rain: report of a workshop.

This report summarizes the potential impact of the acid precipitation phenomenon on human health. There are two major components to this phenomenon: the predepositional phase, during which there is direct human exposure to acidic substances from ambient air, and the post-depositional phase, in which the deposition of acid materials on water and soil results in the mobilization, transport, and even chemical transformation of toxic metals. Acidification increases bioconversion of mercury to methylmercury, which accumulates in fish, increasing the risk to toxicity in people who eat fish. Increase in water and soil content of lead and cadmium increases human exposure to these metals which become additive to other sources presently under regulatory control. The potential adverse health effects of increased human exposure to aluminum is not known at the present time.

The analysis of total and form-variable tin in various media.

Methods for both total and form-variable tin analysis in biological media are reviewed. While total tin analysis was common in the past, and in some cases still is, better understanding of the toxicology and toxicokinetics of organotins in biological systems requires knowledge of specific tin forms present. Both chromatographic and non-chromatographic methods for chemical speciation of organotins in various media have been described, the former appearing to offer the most promising approaches. High performance liquid chromatography (HPLC) in tandem with tin-specific metal detection presently appears to offer the most promise.

New directions in the toxicokinetics of human lead exposure.

An important determinant of body lead (Pb) burden and Pb toxicity in exposed humans is Pb metabolism, or more correctly, Pb toxicokinetics. It affects the former through the quantitative processes of uptake, distribution and retention/excretion and the latter via delivery of toxic doses to cellular/molecular sites of action. Pb toxicokinetics has useful application in understanding Pb's behavior in populations. Several of these applications have been studied and results are presented for the toxicokinetic basis of dose-neurotoxic effect relationships in selected longitudinal studies and the use of toxicokinetic modeling for estimation of body lead burden in early populations. Three well-known, ongoing longitudinal studies of developmental neurotoxicity--in Boston, Cincinnati, and Port Pirie, Australia--involve cohorts who differ markedly as to their pre- and postnatal lead exposure profiles. Toxicokinetic examination of these exposure differences helps to explain the temporal variability seen in blood Pb-toxic effect relationships and supports a causal role for lead. Toxicokinetic models of Pb uptake and in-vivo behavior are increasingly being considered for estimating Pb-B levels in lieu of direct measurement. A linear biokinetic model, using reliable input data for natural/prehistoric levels of Pb in sources, was applied to estimation of prehistoric/preindustrial children's blood lead. A range of 0.06 to 0.12 microgram/dl was estimated for two lead intakes. These estimates are still two orders of magnitude (85 to 165-fold) lower than the newly issued CDC toxicity guideline for children of 10 micrograms/dl. Lastly, the toxicokinetics of lead in bone, particularly its resorption with metabolic stimuli, is of concern, particularly for "baby boom" women who are either of childbearing age or approaching menopause and who had greatly elevated environmental lead exposures in the 1940s to 1970s.

Quantitative analysis of ethyltin compounds in mammalian tissue using HPLC/FAAS.

Measurement of total tin and ethyln tin forms in mammalian tissue is described, using ion-exchange high performance liquid chromatography (HPLC) in tandem with flameless atomic absorption spectrometry (FAAS) for tin-specific detection. All tin forms in whole blood and tissue homogenates were liberated from biological (in vivo) binding by treatment with 6M hydrochloric acid for a period of 4 hr. Ethyln tin species, as the chlorides, were partitioned into chloroform:ethyl acetate (1:1) and analyzed via HPLC using a strong cation exchange column, with fraction collection by a programmable collector and fraction tin measurement by FAAS. Triethyl- and diethyltin were separated and quantitated using 0.167M ammonium citrate in 70:30 methanol:water, while monoethyltin required the use of 0.50M citrate salt in 70:30 water:methanol as mobile phase to effect elution. The difference between total and speciated tin content provides an estimate of remaining tin species, including the inorganic element.

Quantitative analysis of total and trimethyl lead in mammalian tissues using ion exchange HPLC and atomic absorption spectrometric detection.

Measurement of total and trimethyl lead in mammalian tissue is described, using ion exchange/high performance liquid chromatography in tandem with flameless atomic absorption spectrometry for lead-specific detection. All lead forms in whole blood and homogenates of soft tissue--brain, kidney, and liver--were liberated from tissue binding by treatment with dilute (3N) HCl for a period of 18 hr. Trimethyl lead was partitioned into chloroform/ethyl acetate after media neutralization to pH of approximately 4 and saturation with sodium chloride. The extract was chromatographically analyzed on a Partisil SCX-10 cation exchange column, using 0.167M ammonium citrate in methanol:water (70:30) as mobile phase. Fractions of eluate were collected using a programmable fraction collector, and the fractions collected from 3.5 to 5.0 min were analyzed by atomic absorption spectrometry. Total lead in tissue was measured by acid wet digestion and flameless atomic absorption spectrometry. The difference in the values from both analyses provided a measure of any trimethyl lead metabolites.