Biomedical subjects
P Mushak
Publications and source records attributed to P Mushak.
Defining lead as the premiere environmental health issue for children in America: criteria and their quantitative application.
The principal environmental health issue for American children is pervasive lead poisoning from the many decades of lead contamination. Available scientific evidence cementing lead's premiere ranking is voluminous, multifaceted, and compelling. This evidence, however, requires organization into a clear and coherent body of science before it can be fully recognized or comprehended by either the scientific community or the general public and its representatives: public health officials, regulators, policy makers, and legislators. An attempt at such organization is presented and begins with the premise that there exist clear, objective criteria by which a premiere environmental health issue can be defined. A second premise is that these criteria sort themselves into three categories which cover the full spectrum of toxic contaminant-population relationships. They are: (1) economic and sociopolitical, (2) scientific and public health, and (3) societal risk assessment criteria. The first set of criteria includes economic and historical centrality, primacy of economic over public health considerations, a relatively narrow decision-making framework, and controlled flow of information on the toxicant, especially its negative impacts. The second set of criteria is also orthodox in scope: the toxicant should be indestructible, should accumulate in both the environment and the body, and should be a multimedia contaminant; it should produce toxicity in numerous organs with little impediment; toxicity should be produced with low/no threshold in huge numbers of the most vulnerable; and finally, effects should persist in the critical target organ(s). There is a third, more globally encompassing, set of criteria important for present-day requirements for risk assessment; e.g., the contaminant should produce full-spectrum population-wide as well as individual toxicity. Evidence for societal harm should be compelling. It should typify the increasing importance of the elements of preventive over clinical medicine and the substance should bring to bear the cost-benefit analysis of macro plus micro health risk. Lead exposure and toxicity is conclusively shown to meet ALL of these criteria and is the premiere environmental health threat to America's children.
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)
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.
Determination of numbers of lead-exposed American children as a function of lead source: integrated summary of a report to the U.S. Congress on childhood lead poisoning.
In 1986, the U.S. Congress [Section 118(f), Superfund Amendments and Reauthorization Act (SARA)] directed the Agency for Toxic Substances and Disease Registry to provide to it a quantitative assessment of the contributions of various sources of lead to childhood exposure. We provided both a quantitative response to the mandate and a critique of low-level lead sources for U.S. population segments. We also present here an integrated assessment of major and low-level lead sources. Significant sources of lead in childhood exposure include lead in paint, dust, soil, and drinking water. Approximately 6 million U.S. children less than 7 years old reside in the oldest housing, with highest exposure risk due to leaded paint. About 2 million in deteriorated units are at particularly high risk for exposure with ca. 1.2 million children in oldest, deteriorated housing estimated to have blood lead (PbB) levels above 15 micrograms/dl. Soil and dust lead are potential sources of exposure for 6-12 million children. Residential tap water lead is a measurable source for ca. 3.8 million children, of whom the U.S. EPA estimates ca. 240,000 have water-specific exposures at toxic levels. Leaded gasoline combustion mainly in past years has produced, and will continue to produce into the 1990s, significant numbers of exposed children with toxicologically elevated PbBs. For 1990, 1.25 million children will have their PbBs fall below 15 micrograms/dl. Food lead can cause significant exposure in certain cases.
Prenatal and postnatal effects of low-level lead exposure: integrated summary of a report to the U.S. Congress on childhood lead poisoning.
This article provides an integrated summary of a report to Congress from the Federal government (ATSDR) on childhood lead poisoning in the United States, with particular reference to low-level lead exposure and its effects on the fetus and the preschool child. As mandated by Section 118(f)(1)(C) of the 1986 Superfund Amendments and Reauthorization Act (SARA), ATSDR has examined the full spectrum of human in utero and postnatal lead toxicity, with emphasis on low-level neurotoxicity and adverse impacts on growth indices in risk populations. Especially important has been assessment of the relative persistence of these effects in later life as discernible from a number of longitudinal studies now under way around the world. Included in the Congressional report were discussions of dose-effect and dose-response relationships using blood lead levels as the indicator of lead dose.
Specification of metals and metal compounds: implications for biological monitoring and development of regulatory approaches.
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Distribution and retention of organic and inorganic mercury in methyl mercury-treated neonatal rats.
Seven-day-old Long Evans rats received one mumol of 203Hg-labeled methyl mercury/kg sc and whole body retention and tissue distribution of organic and inorganic mercury were examined for 32 days postdosing. Neonates cleared mercury slowly until 10 days postdosing when the clearance rate abruptly increased. During the interval when whole body clearance of mercury was extremely slow, methyl mercury was metabolized to inorganic mercury. Peak concentration of mercury in kidney occurred at 2 days postdosing. At 32 days postdosing, 8% of mercury in kidney was in an organic from. Liver mercury concentration peaked at 2 days postdosing and organic mercury accounted for 38% at 32 days postdosing. Brain concentrations of mercury peaked at 2 days postdosing. At 10 days postdosing, organic mercury accounted for 86% of the brain mercury burden, and, at 32 days postdosing, for 60%. The percentage of mercury body burden in pelt rose from 30 to 70% between 1 and 10 days postdosing. At 32 days postdosing pelt contained 85% of the body burden of mercury. At all time points, about 95% of mercury in pelt was in an organic form. Compartmental analysis of these data permitted development of a model to describe the distribution and excretion of organic and inorganic mercury in methyl mercury-treated neonatal rats.
Sexual differences in the excretion of organic and inorganic mercury by methyl mercury-treated rats.
Adult male and female Long Evans rats received 1 mumole of methyl (203Hg) mercuric chloride per kilogram sc. Whole-body retention of mercury and excretion of organic and inorganic mercury in urine and feces were monitored for 98 days after dosing. Females cleared mercury from the body more rapidly than did males. The major route of mercury excretion was feces. By 98 days after dosing, cumulative mercury excretion in feces accounted for about 51% of the dose in males and about 54% of the dose in females. For both sexes, about 33% of the dose was excreted in feces as inorganic mercury. Cumulative excretion of organic mercury in feces accounted for about 18 and 21% of the dose in males and females, respectively. Urinary excretion of mercury was quantitatively a smaller route for mercury clearance but important sexual differences in loss by this route were found. Over the 98-day experimental period, males excreted in urine about 3.2% of the dose and females excreted 7.5%. Cumulative organic Hg excretion in urine accounted for 1.8% of the dose in males and 5.3% of the dose in females. These sexual differences in urinary and fecal excretion of organic and inorganic mercury following methyl mercury treatment were consistent with previous reports of sexual differences in mercury distribution and retention in methyl mercury-treated rats, particularly sexual differences in organic mercury uptake and retention in the kidney. Relationships between body burdens of organic or inorganic Hg and output of these forms of Hg in urine and feces were also found to be influenced by the interval after MeHg treatment and by sex. Relationship between concentration of Hg in liver and feces and in kidney and urine differed for organic and inorganic Hg and depended upon sexual status and interval after MeHg treatment. These findings emphasize that sexual differences in distribution, retention, and metabolism of methyl mercury are factors to be considered in estimations of hazards associated with exposure to this agent.
Effects of cadmium exposure on zinc and copper distribution in neonatal rats.
Tissue zinc and copper concentrations undergo marked changes in the neonatal rat during the first several weeks of life and it was of considerable interest to study the effect of cadmium exposure on these ontogenic changes. Long evans rats received either 2 or 10 mumol cadmium chloride per kg SC at 9 days of age and were sacrificed at 20 or 36 days of age. Tissue copper and zinc concentrations in cadmium-treated rats were compared to those of age-matched controls for statistically significant changes. The tissue affected, the element altered and the direction of change in concentration, increased (+) or decreased (-), are summarized for the two dosing groups (age at dosing, age at sacrifice in days): 2 mumol/kg (9, 20): kidney Zn (+), blood Zn (-), cerebral Cu (-), cerebellar Cu (+); 2 mumol/kg (9, 36): blood Zn (-); 10 mumol/kg (9, 20); liver, kidney, cerebral and cerebellar and blood Zn (-), cerebellar Cu (+); 10 mumol/kg (9, 36): liver and heart Zn (+), blood Zn (-); liver and heart Zn (+), blood Zn (-); kidney, cerebral, cerebellar and heart Cu (+). Changes in tissue zinc or copper concentrations produced by cadmium treatment could not be accounted for by the direct replacement of these elements by cadmium and may be due to alterations in transport of these elements. These results indicate that early life exposure to low levels of cadmium can have large and persistent effects on the distribution of the essential metals, copper and zinc.
Sexual differences in the distribution and retention of organic and inorganic mercury in methyl mercury-treated rats.
At 56 days of age, male and female Long-Evans rats received 1 mumole of 203Hg-labeled methyl mercuric chloride per kilogram sc and total, organic, and inorganic mercury contents and concentrations in tissues were determined for up to 98 days postdosing. Whole body clearance of mercury was faster in females than in males, and females attained higher peak percentages of the methyl mercury dose in kidney and brain than did males. Females had significantly higher mean percentages of the mercury dose present in the kidney and brain as organic or total mercury and in brain as inorganic mercury than did males. Males had significantly higher mean percentages of the dose present as organic or total mercury in pelt and whole body than did females. When expressed on a concentration basis, the only significant sexual difference was in the higher average concentration of organic mercury in the kidneys of females. When expressed on a tissue content basis, significant male-female differences in the kinetics (sex X time interactions) of organic mercury retention were found in kidney, brain, skeletal muscle, pelt, and whole body. Significant sex X time interactions in the concentrations of organic mercury were found in kidney, skeletal muscle, and whole body. Kinetics of retention and concentration of inorganic Hg in the pelt differed significantly for males and females. Discordance in degree of statistical significance of differences in mercury contents and concentrations reflected in part differences in relative body composition of males and females. Integrated exposures of tissues of males and females to organic or inorganic mercury were determined by fitting multiexponential retention functions to retention data. Differences in integrated exposure were estimated by the female-to-male ratio of areas under retention curves. Reconstruction of whole body organic and inorganic mercury burdens from constituent tissues indicated that integrated exposures of males and females to inorganic mercury were equal but females had a lower integrated exposure to organic mercury. Integrated exposure of liver to either form of mercury was about equal in males and females. However, the integrated exposure of the brain of females to inorganic mercury was 2.19 times that of males suggesting a sexual difference in accumulation or retention of inorganic mercury in the nervous system. These sexual differences in distribution and retention of organic and inorganic mercury after methyl mercury exposure may underlie reported sexual differences in sensitivity to the toxic effects of methyl mercury.
Relation of lead and social factors to IQ of low-SES children: a partial replication.
An independent replication of a previous study (Schroeder et al., 1985) of the effects of interactive social environmental factors on the relationship of lead and Stanford-Binet IQ was performed on 75 of 80 low-SES black children screened by county health departments in North Carolina. Children's mean blood lead (PbB) level was 20.8 micrograms/dl (range, 6.3 to 47.4). Multivariate regression analyses showed no significant interactions between PbB and age, sex, maternal IQ, Caldwell home environment score, or SES (Hollingshead Two-Factor Index). There was a highly significant negative relationship between both mean and maximum PbB levels with IQ, p less than .002; that is, IQ decreased linearly as PbB increased. The most accurate and precise regression model included lead, maternal IQ, home environment, and gender.
Separating the effects of lead and social factors on IQ.
Initial evaluations of 104 low-socioeconomic status black children screened by the local community health departments in North Carolina showed significant effects of lead in the range 6-59 micrograms/dl on IQ after controlling for concomitant social factors, such as socioeconomic status, home environment, and maternal IQ. The main concomitant variable was socioeconomic status, which was multicolinear with other social factors. Five years later, when all blood lead levels were 30 micrograms/dl or less, lead effects on IQ were no longer significant. The correlation between maternal and child IQ, which had been suppressed initially in children with higher lead levels, returned to expected levels when decreases in blood lead level occurred, while concomitant variables remained stable over the 5-year period.
5-year follow-up study of children with low-to-moderate lead absorption: electrophysiological evaluation.
Forty-nine children aged 6 to 12 years were evaluated for residual effects of lead exposure using psychometric, electrophysiological, and medical tests 5 years after initial assessment. The original range of blood lead (PbB) levels was 6-59 (mean = 28) micrograms/dl; the current range was 6-30 (mean = 14) micrograms/dl. A linear relationship between PbB and slow brain wave voltage during sensory conditioning was observed at initial evaluation and at 2-year follow-up. No significant relationship between PbB and slow wave voltage during passive conditioning was found at the 5-year follow-up, although a linear increase in slow wave negativity relative to the current PbB level during active conditioning was suggested by exploratory analyses. Another exploratory analysis revealed a significant linear relationship between the original PbB levels and the latency of waves III and V of the brainstem auditory evoked potential. The latency of both waves increased as a function of original PbB. Increased latency of these waves is suggestive of subclinical pathology of the auditory pathway rostral to the cochlear nucleus, although end-organ impairment cannot be ruled out. No threshold for the effect of Pb on auditory function was apparent.
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.
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.