Cadmium, lead, and thallium in mainstream tobacco smoke particulate.

The deliveries of cadmium, thallium, and lead in mainstream smoke particulate from cigarettes with different smoke delivery designs were determined by inductively coupled plasma-mass spectrometry in order to investigate their impact on the delivery of these known toxic compounds. Analyses showed that the levels of all three metals in smoke particulate were associated with their tar delivery category. After normalizing the metal concentrations to tar, there were no longer any statistically significant delivery differences between full-flavor, light or ultra-light cigarettes. When the concentrations were normalized to nicotine, the mean levels from the three delivery groups were much smaller than before normalization. But unlike the case using tar to normalize, in some of the cases, there were still some statistically significant differences in the nicotine-normalized results. These findings suggest that if smokers compensate for differences in nicotine intake, they receive exposures to toxic heavy metals from ultra-light, light and full-flavor cigarettes that are more similar than results would suggest from using the Federal Trade Commission method alone.

Hepatitis C virus nonstructural 5A protein induces interleukin-8, leading to partial inhibition of the interferon-induced antiviral response.

Hepatitis C virus (HCV), a major cause of liver disease worldwide, is frequently resistant to the antiviral alpha interferon (IFN). The HCV nonstructural 5A (NS5A) protein has been implicated in HCV antiviral resistance in many studies. NS5A antagonizes the IFN antiviral response in vitro, and one mechanism is via inhibition of a key IFN-induced enzyme, the double-stranded-RNA-activated protein kinase (PKR). In the present study we determined if NS5A uses other strategies to subvert the IFN system. Expression of full-length NS5A proteins from patients who exhibited a complete response (FL-NS5A-CR) or were nonresponsive (FL-NS5A-NR) to IFN therapy in HeLa cells had no effect on IFN induction of IFN-stimulated gene factor 3 (ISGF-3). Expression of mutant NS5A proteins lacking 110 (NS5A-DeltaN110), 222 (NS5A-DeltaN222), and 334 amino-terminal amino acids and mutants lacking 117 and 230 carboxy-terminal amino acids also had no effect on ISGF-3 induction by IFN. Expression of FL-NS5A-CR and FL-NS5A-NR did not affect IFN-induced STAT-1 tyrosine phosphorylation or upregulation of PKR and major histocompatibility complex class I antigens. However, NS5A expression in human cells induced interleukin 8 (IL-8) mRNA and protein, and this effect correlated with inhibition of the antiviral effects of IFN in an in vitro bioassay. NS5A induced transcription of a reporter gene driven by the IL-8 promoter, and the first 133 bp of the IL-8 promoter made up the minimal domain required for NS5A transactivation. NS5A-DeltaN110 and NS5A-DeltaN222 stimulated the IL-8 promoter to higher levels than did the full-length NS5A protein, and this correlated with increased nuclear localization of the proteins. Additional mutagenesis of the IL-8 promoter suggested that NF-kappaB and AP-1 were important in NS5A-DeltaN222 transactivation in the presence of tumor necrosis factor alpha and that NF-IL-6 was inhibitory to this process. This study suggests that NS5A inhibits the antiviral actions of IFN by at least two mechanisms and provides the first evidence for a biological effect of the transcriptional activity of the NS5A protein. During HCV infection, viral proteins may induce chemokines that contribute to HCV antiviral resistance and pathogenesis.

Exposure of the U.S. population aged 6 years and older to cadmium: 1988-1994.

Cadmium was measured in urine specimens from 22,162 participants in the Third National Health and Nutrition Examination Survey (NHANES III 1988-1994). Urine cadmium, expressed either as uncorrected (microg/L) or creatinine corrected (microg/g creatinine) increased with age and with smoking. The arithmetic mean value for urine cadmium in the U.S. population was 0.57 microg/L or 0.48 microg/g creatinine. Based on our estimates, about 2.3% of the U.S. population have urine cadmium concentrations greater than 2 microg/g creatinine, and 0.2% have concentrations greater than 5 microg/g creatinine, the current World Health Organization health-based exposure limit.

Uranium and thorium in urine of United States residents: reference range concentrations.

We measured uranium and thorium in urine of 500 U. S. residents to establish reference range concentrations using a magnetic-sector inductively coupled argon plasma mass spectrometer (ICP-MS). We found uranium at detectable concentrations in 96.6% of the urine specimens and thorium in 39.6% of the specimens. The 95th percentile concenetration for uranium was 34.5 ng/L (parts per trillion); concentrations ranged up to 4080 ng/L. Thorium had a 95th percentile concentration of 3.09 ng/L; concentrations ranged up to 7.7 ng/L.

Characterization of the effects of hepatitis C virus nonstructural 5A protein expression in human cell lines and on interferon-sensitive virus replication.

The hepatitis C virus (HCV) nonstructural 5A (NS5A) protein has been implicated in the inherent resistance of HCV to interferon (IFN) antiviral therapy in clinical studies. Biochemical studies have demonstrated that NS5A interacts in vitro with and inhibits the IFN-induced, RNA-dependent protein kinase, PKR, and that NS5A interacts with at least one other cellular kinase. The present study describes the establishment and characterization of various stable NS5A-expressing human cell lines, and the development of a cell culture-based assay for determining the inherent IFN resistance of clinical NS5A isolates. Human epithelioid (Hela) and osteosarcoma (U2-OS) cell lines were generated that express NS5A under tight regulation by the tetracycline-dependent promoter. Maximal expression of NS5A occurred at 48 hours following the removal of tetracycline from the culture medium. The half-life of NS5A in these cell lines was between 4 to 6 hours. NS5A protein expression was localized cytoplasmically, with a staining pattern consistent with the location of the Golgi apparatus and endoplasmic reticulum. In the majority of cell lines, no obvious phenotypic changes were observed. However, three genotype 1b NS5A-expressing osteosarcoma cell lines exhibited cytopathic effect and severely reduced proliferation as a result of high-level NS5A expression. Full-length NS5A protein isolated from a genotype 1b IFN-nonresponsive patient (NS5A-1b) was capable of rescuing encephalomyocardititis virus replication during IFN challenge up to 40-fold, whereas a full-length NS5A-1a and an interferon sensitivity determining region (ISDR) deletion mutant (NS5A-1a-triangle upISDR) isolated from a genotype 1a IFN-nonresponsive patient showed no rescue activity. The NS5A-1b and NS5A-1a proteins also rescued vesicular stomatitis virus replication during IFN treatment by two- to threefold. These data cummulatively suggest that NS5A expression alone can render cells partially resistant to the effects of IFN against IFN-sensitive viruses, and that in some systems, these effects may be independent of the putative ISDR. A scenario is discussed in which the NS5A protein may employ multiple strategies contributing to IFN resistance during HCV infection.

Exposure of the U.S. population to lead, 1991-1994.

Blood lead measurements were obtained on 13,642 persons aged 1 year and older who participated in Phase 2 of the Third National Health and Nutrition Examination Survey (NHANES III) from 1991 through 1994. NHANES III is a national representative survey of the civilian, noninstitutionalized U.S. population. The overall mean blood lead level for the U.S. population aged 1 year and older was 2.3 microgram/dl, with 2.2% of the population having levels >=10 microgram/dl, the level of health concern for children. Among U.S. children aged 1-5 years, the mean blood lead level was 2.7 microgram/dl, and 890,000 of these children (4.4%) had elevated blood lead levels. Sociodemographic factors associated with higher blood lead levels in children were non-Hispanic black race/ethnicity, low income, and residence in older housing. The prevalence of elevated blood lead levels was 21.9% among non-Hispanic black children living in homes built before 1946 and 16.4% among children in low-income families who lived in homes built before 1946. Blood lead levels continue to decline in the U.S. population, but 890,000 children still have elevated levels. Public health efforts have been successful in removing lead from population-wide sources such as gasoline and lead-soldered food and drink cans, but new efforts must address the difficult problem of leaded paint, especially in older houses, as well as lead in dust and soil. Lead poisoning prevention programs should target high-risk persons, such as children who live in old homes, children of minority groups, and children living in families with low income.

Profiles of Great Lakes critical pollutants: a sentinel analysis of human blood and urine. The Great Lakes Consortium.

To determine the contaminants that should be studied further in the subsequent population-based study, a profile of Great Lakes (GL) sport fish contaminant residues were studied in human blood and urine specimens from 32 sport fish consumers from three Great Lakes: Lake Michigan (n = 10), Lake Huron (n = 11), and Lake Erie (n = 11). Serum was analyzed for 8 polychlorinated dioxin congeners, 10 polychlorinated furan congeners, 4 coplanar and 32 other polychlorinated biphenyl (PCB) congeners, and 11 persistent chlorinated pesticides. Whole blood was analyzed for mercury and lead. Urine samples were analyzed for 10 nonpersistent pesticides (or their metabolites) and 5 metals. One individual was excluded from statistical analysis because of an unusual exposure to selected analytes. Overall, the sample (n = 31) consumed, on average, 49 GL sport fish meals per year for a mean of 33 years. On average, the general population in the GL basin consume 6 meals of GL sport fish per year. The mean tissue levels of most persistent, bioaccumulative compounds also found in GL sport fish ranged from less than a twofold increase to that of PCB 126, which was eight times the selected background levels found in the general population. The overall mean total toxic equivalent for dioxins, furans, and coplanar PCBs were greater than selected background levels in the general population (dioxins, 1.8 times; furans, 2.4 times; and coplanar PCBs, 9.6 times). The nonpersistent pesticides and most metals were not identified in unusual concentrations. A contaminant pattern among lake subgroups was evident. Lake Erie sport fish consumers had consistently lower contaminant concentrations than consumers of sport fish from Lake Michigan and Huron. These interlake differences are consistent with contaminant patterns seen in sport fish tissue from the respective lakes; GL sport fish consumption was the most likely explanation for observed contaminant levels among this sample. Frequent consumers of sport fish proved to be effective sentinels for identifying sport fish contaminants of concern. In the larger study to follow, serum samples will be tested for PCBs (congener specific and coplanar), DDE, dioxin, and furans.

Trace metals in urine of United States residents: reference range concentrations.

We measured 13 metals in the urine of 496 United States residents to establish reference range concentrations using inductively coupled argon plasma mass spectrometry and Zeeman graphite furnace atomic absorption spectrometry. We frequently found 8 of these analytes at detectable concentrations in urine specimens: molybdenum (in 99.8%); lead (98.8%); tin (89%); thallium (77%); antimony (73.5%); manganese (73%); cesium (71%); tungsten (70%); and platinum (69.7%). The 95th percentile concentration for molybdenum was 168 micrograms/L; concentrations ranged up to 688 micrograms/L. Lead concentrations ranged up to 67 micrograms/L, and the 95th upper percentile was 6.4 micrograms/L. Tin had 95th upper percentile of 20.1 micrograms/L. Other analytes measured at detectable concentrations included barium (in 67% of the specimens); beryllium (67%); chromium (54%); thorium (44%); and cobalt (43%). In almost every case, the 95th upper percentiles of these analytes were less than 15 micrograms/L.

Creating and implementing guidelines on caring for difficult patients: a research utilization project.

Difficult patients challenge the resourcefulness of nurses. Considering the results of a focus group study, guidelines are designed for the care of difficult patients. Four case studies present the use of the guidelines, including interventions and outcomes.

Lead Exposure among Adult Temporary Residents in Eastern Europe: Should Blood Lead Levels Be Monitored?

Background: The risk of lead exposure among temporary residents in Eastern Europe is unknown. We monitored blood lead levels (BLLs) of Peace Corps Volunteers serving in Albania, Bulgaria, the Czech Republic, Hungary, Poland, Romania, and Slovakia from June 1991 through June 1994. Methods: BLLs were analyzed before the Volunteers left the United States (Sample 1), at mid-service (median of 15 months in-country, Sample 2), and at end-of-service (median of 22 months in-country, Sample 3). Results: Among 425 study participants who provided at least one follow-up blood sample, BLLs were significantly higher at Samples 2 and 3 compared to the U.S. baseline (paired t-test, p<.0001); however, the mean increase in BLL was only 1.0 ug/dL (range = -9.6 to 10.7). Overall, 74% of Volunteers experienced an increase in BLLs, 24% a decrease in BLLs, and 2% no change in BLLs at Sample 3 compared to their U.S. baseline. The highest increases in BLLs were among Volunteers in Albania, Bulgaria, and Romania (analysis of variance, p<.0001). In addition, men had higher mean increases in BLLs at Samples 2 and 3 compared to women (t-test, p=.017 and.029). Conclusions: The risk of significant lead exposure among our study population was low, and monitoring of BLLs among adult short-term residents in Eastern Europe does not seem to be indicated.

Mercury exposure in high school chemistry teachers.

To assess whether high school chemistry teachers had higher urinary mercury concentrations than other high school teachers, 24 high school teachers from nine schools in northeastern Ohio were studied. First morning voided urine samples and air samples from the teachers' classrooms were analyzed for total mercury content by cold vapor atomic absorption. The median adjusted urinary mercury concentration in the 12 chemistry teachers was 4.6 microg/g creatinine (range 2.2-8.2 microg/g creatinine) and it was 6.3 microg/g creatinine in the 12 non-chemistry teachers. All classroom air samples contained mercury levels below detection limits. No evidence was provided that high school chemistry teachers are at increased risk of chronic mercury exposure from their teaching activities compared to other high school teachers.

Reference range data for assessing exposure to selected environmental toxicants.

We analyzed blood and urine specimens from 32 charter boat captains, anglers, and spouses from both groups, who reportedly ate fish from Lakes Michigan, Huron, or Erie, for selected environmental toxicants. The toxicants measured in serum were polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), coplanar polychlorinated biphenyls, other polychlorinated biphenyls (PCBs), and persistent pesticides. Nonpersistent pesticides and elements were measured in urine; and elements were measured in blood. Internal dose levels of these toxicants will be compared to reference range data that we have compiled. These reference range data will be used to ascertain the exposure status of individuals or groups within this study.

Blood lead levels in the US population. Phase 1 of the Third National Health and Nutrition Examination Survey (NHANES III, 1988 to 1991)

OBJECTIVE: To determine mean blood lead levels and their sociodemographic correlates in the US population. DESIGN: Nationally representative cross-sectional health examination survey that included measurements of venous blood lead. PARTICIPANTS: A total of 13,201 persons aged 1 year and older examined during phase 1 of the third National Health and Nutrition Examination Survey (1988 to 1991). RESULTS: The overall mean blood lead level for the US population was 0.14 mumol/L (2.8 micrograms/dL). Blood lead levels were consistently higher for younger children than for older children, for older adults than for younger adults, for males than for females, for blacks than for whites, and for central-city residents than for non-central-city residents. Other correlates of higher blood lead levels included low income, low educational attainment, and residence in the Northeast region of the United States. National estimates for children 1 to 5 years of age indicate that 8.9%, or approximately 1.7 million children, have blood lead levels 0.48 mumol/L (10 micrograms/dL) or greater. These levels are high enough to be of health concern under 1991 Centers for Disease Control and Prevention guidelines. CONCLUSIONS: The low overall mean blood lead levels demonstrate a major public health success in primary prevention efforts. However, exposure to lead at levels that may adversely affect the health of children remains a problem especially for those who are minority, urban, and from low-income families. Strategies to identify the most vulnerable risk groups are necessary to further reduce lead exposure in the United States.

The decline in blood lead levels in the United States. The National Health and Nutrition Examination Surveys (NHANES)

OBJECTIVE: To describe trends in blood lead levels for the US population and selected population subgroups during the time period between 1976 and 1991. DESIGN: Two nationally representative cross-sectional surveys and one cross-sectional survey representing Mexican Americans in the southwestern United States. SETTING/PARTICIPANTS: Participants in two national surveys that included blood lead measurements: the second National Health and Nutrition Examination Survey, 1976 to 1980 (n = 9832), and phase 1 of the third National Health and Nutrition Examination Survey, 1988 to 1991 (n = 12,119). Also, Mexican Americans participating in the Hispanic Health and Nutrition Examination Survey, 1982 to 1984 (n = 5682). RESULTS: The mean blood lead level of persons aged 1 to 74 years dropped 78%, from 0.62 to 0.14 mumol/L (12.8 to 2.8 micrograms/dL). Mean blood lead levels of children aged 1 to 5 years declined 77% (0.66 to 0.15 mumol/L [13.7 to 3.2 micrograms/dL]) for non-Hispanic white children and 72% (0.97 to 0.27 mumol/L [20.2 to 5.6 micrograms/dL]) for non-Hispanic black children. The prevalence of blood lead levels 0.48 mumol/L (10 micrograms/dL) or greater for children aged 1 to 5 years declined from 85.0% to 5.5% for non-Hispanic white children and from 97.7% to 20.6% for non-Hispanic black children. Similar declines were found in population subgroups defined by age, sex, race/ethnicity, income level, and urban status. Mexican Americans also showed similar declines in blood lead levels of a slightly smaller magnitude over a shorter time. CONCLUSIONS: The results demonstrate a substantial decline in blood lead levels of the entire US population and within selected subgroups of the population. The major cause of the observed decline in blood lead levels is most likely the removal of 99.8% of lead from gasoline and the removal of lead from soldered cans. Although these data indicate major progress in reducing lead exposure, they also show that the same sociodemographic factors continue to be associated with higher blood lead levels, including younger age, male sex, non-Hispanic black race/ethnicity, and low income level. Future efforts to remove other lead sources (eg, paint, dust, and soil) are needed but will be more difficult than removing lead from gasoline and soldered cans.

Chronic renal effects in three studies of men and women occupationally exposed to cadmium.

We measured sensitive indicators of renal damage in three different populations occupationally exposed to cadmium, and examined the degree of variation in damage and the relative sensitivity of different types of indicators. The three studies included (1) men exposed in a cadmium recovery plant, (2) men exposed in a nickel/cadmium battery plant, and (3) women exposed in the latter plant. The indicators of renal damage were urinary proteins in three categories: (1) the high molecular weight enzymes alanine aminopeptidase (AAP) and N-acetyl-beta-D-glucosaminidase (NAG), (2) the intermediate molecular weight protein albumin (ALB), and (3) the low molecular weight proteins retinol-binding protein (RBP) and beta 2-microglobulin (B2M). These tests indicate that exposed groups with higher urine cadmium levels had varying degrees of renal damage. All exposed groups showed evidence of renal damage when compared with their respective control groups. A higher percentage of elevated protein levels was noted in the exposed group of Study 1 than in the exposed groups of Studies 2 and 3. In Study 1, the means of all five protein levels and ALB, RBP, and B2M fractional clearances were significantly elevated in the group with higher urine cadmium concentrations when compared with the groups with lower urine cadmium concentrations. Highly significant dose-response relationships for all of the urinary protein tests, including fractional clearances, were found. All of the tests were more sensitive in detecting evidence of subclinical renal damage than serum creatinine, a commonly used indicator of renal function. The order of test sensitivity in men was determined by considering three factors: (1) the magnitude of the correlation coefficient between the test and the urine cadmium concentration in the study with the most advanced damage, (2) the relative cadmium level predicted by the dose-response model at which there is a 10% chance of observing an elevated test value, and (3) the ability of the tests to detect renal effects in the population with less advanced damage. The tests in order of decreasing sensitivity in men are ALB, AAP, NAG, RBP approximately B2M. The women with higher urine cadmium levels in Study 3 had a higher percentage of elevated AAP and NAG values when compared with the control group.

An outbreak of a food-related illness resembling boric acid poisoning.

An outbreak of an illness suggestive of boric acid poisoning occurred among 51 persons who had eaten lunch at the cafeteria of the United States Agency for International Development in Islamabad, Pakistan, on February 11, 1990. Affected patients had headache and severe myalgias 2 to 4 hours after eating lunch. Fever, nausea and vomiting, red eyes, and photophobia were also reported. Among 25 patients (49%), a sunburn-like inflammation of the skin of the face developed, which subsequently desquamated. One patient required hospitalization for 1 day because of dehydration. Among all patients, the only symptoms remaining 72 hours after the meal were mild headache, fatigue, and peeling skin. Those persons who became ill were more likely to have eaten one particular food item (minestrone soup) for lunch than were those who did not become ill. A similar illness has been described following ingestion of boric acid. However, the results of an analysis of serum samples collected 3 days after the lunch from 24 patients did not show boron above normal background levels. Because of boron's short half-life, however, these data do not rule out the possibility that patients may have had higher boron levels at the onset of the illness.

Mercury exposure from interior latex paint.

BACKGROUND: Many paint companies have used phenylmercuric acetate as a preservative to prolong the shelf life of interior latex paint. In August 1989, acrodynia, a form of mercury poisoning, occurred in a child exposed to paint fumes in a home recently painted with a brand containing 4.7 mmol of mercury per liter (at that time the Environmental Protection Agency's recommended limit was 1.5 mmol or less per liter). METHODS: To determine whether the recent use of that brand of paint containing phenylmercuric acetate was associated with elevated indoor-air and urinary mercury concentrations, we studied 74 "exposed" persons living in 19 homes recently painted with the brand and 28 "unexposed" persons living in 10 homes not recently painted with paint containing mercury. RESULTS: The paint samples from the homes of exposed persons contained a median of 3.8 mmol of mercury per liter, and air samples from the homes had a median mercury content of 10.0 nmol per cubic meter (range, less than 0.5 to 49.9). No mercury was detected in paint or air samples from the homes of unexposed persons. The median urinary mercury concentration was higher in the exposed persons (4.7 nmol of mercury per millimole of creatinine; range, 1.4 to 66.5) than in the unexposed persons (1.1 nmol per millimole; range, 0.02 to 3.9; P less than 0.001). Urinary mercury concentrations within the range that we found in exposed persons have been associated with symptomatic mercury poisoning. CONCLUSIONS: We found that potentially hazardous exposure to mercury had occurred among persons whose homes were painted with a brand of paint containing mercury at concentrations approximately 2 1/2 times the Environmental Protection Agency's recommended limit.

Determination of nickel in urine with graphite furnace AAS using Zeeman correction.

We have developed a rapid and direct method for determining urine nickel. The urine specimen is diluted (1 + 1) with 2.0% v/v nitric acid and 0.001% v/v Triton X-100 and absorbance measurements are made with Zeeman-effect graphite furnace atomic absorption. The method is sensitive enough to be used to evaluate "normal" subjects for baseline studies or to evaluate environmental or other nonoccupational exposure to nickel. The characteristic mass (pg/0.0044A.s) is 26 pg, which is comparable to that obtained for aqueous solutions. The observed absorbance is linear up to about 100 micrograms l-1, after which the calibration curve departs from linearity. Procedures are described to rigorously exclude nickel contamination. We evaluated precision and accuracy with a U.S. National Bureau of Standards urine reference material. SRM 2670, with an informational nickel value of 70 micrograms l-1, and with a multielement water reference material, SRM 1643b, with a certified nickel value of 49 ng g-1. Within- and among-run standard deviations for SRM 2670 were calculated to be 9.0 and 2.45 micrograms l-1, respectively, and 2.1 and 1.1 micrograms l-1 for SRM 1643b. The detection limit, calculated as 3 SD of a "low" concentration urine, is about 1.1 micrograms l-1. The proposed method was applied to the determination of nickel in urine of 258 workers in a magnet manufacturing plant, and the data obtained support the usefulness of urine nickel for biological monitoring.