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Biomedical subjects

P B Ryan

Publications and source records attributed to P B Ryan.

At least 19 recordsLinked to original sources

A longitudinal investigation of aggregate oral intake of copper.

Four-day composite solid food and beverage duplicate plates and 1-L samples of drinking water were collected from a stratified random sample of 80 individuals as part of the National Human Exposure Assessment Survey in Maryland. The media were obtained from each participant in up to six equally spaced sampling cycles over a year and analyzed for copper by inductively coupled plasma mass spectrometry. Copper concentrations (microg/kg) and consumption rates (kg/d) of solid food, beverage and drinking water were used to derive average daily aggregate oral intake of copper (microg/d). The mean aggregate copper intake of 263 measurements obtained from 68 people was 923.2 +/- 685.6 microg/d (mean +/- SD). Intake through solid food accounted for the majority of aggregate daily intake of copper contributing 87% on average. According to results from mixed model analysis of variance procedures, the mean log-transformed average daily copper intake in each medium except beverage exhibited significant (P < 0.05) variability among sampling cycles. Between-person variability accounted for 50% of the total variance in aggregate copper intake. As measured by the coefficient of variation, distributions of copper intake consisting of one observation per individual were more variable than the distribution consisting of the long-term average intake for each person. These results suggest that estimates of the fraction of a population at risk from chronic copper deficiency or excess copper intake can be overestimated if based upon short-term measures of copper intake. In addition, these results indicate that longitudinal information is required for accurate assessment of aggregate oral intake of copper for an individual.

Administration, Oral↗

Analysis of dietary intake of selected metals in the NHEXAS-Maryland investigation.

As part of a large pilot investigation of multimedia exposure to several classes of environmental contaminants, the National Human Exposure Assessment Survey (NHEXAS)-Maryland study, we collected 388 semiquantitative food checklists and duplicate diet solid food samples, analyzed for arsenic, cadmium, chromium, and lead concentrations, from 80 individuals in Maryland in 1995-1996 in a repeated measures design. Here we explore several methods to infer foods most strongly associated with concentrations of these metals observed in the duplicate diet in our data set. We employed two techniques in which logarithmically transformed metal concentrations in the duplicate diet were regressed on individual food item consumption using algorithms designed to identify the foods most associated with the observed duplicate diet concentrations. We also employed an alternative strategy in which foods to be used as independent variables in regression were selected using data collected in national food consumption and residue surveys, with regression procedures proceeding with the selected foods in a similar manner. The concordance of foods selected as major predictors among these three techniques is noteworthy and is discussed. Finally, the Dietary Exposure Potential Model (DEPM) was used with the Dietary Checklist data to predict duplicate diet concentrations within our sample. A comparison between the predicted values and those observed gave R(2) values of 0.180, 0.206, and 0.076 for As, Cd, and Pb, respectively (p < 0.0001 in all cases). We discuss the significance of these observations and the implications for dietary-exposure-based risk analysis and dietary intake epidemiology.

Arsenic↗

Longitudinal investigation of dietary exposure to selected pesticides.

Between September 1995 and September 1996, 4-day composite duplicate plate samples (379 solid food samples and 303 beverage samples) were obtained from a stratified random sample of 75 individuals in Maryland and analyzed for the presence of 10 pesticides. Samples were collected in each of six approximately equally spaced cycles as part of a larger pilot investigation of longitudinal exposure to pesticides and other elements. Chlorpyrifos was detected in 38.3% of the solid food samples, malathion in 75.2%, and p,p'-DDE in 21.4%. Other pesticides were detected in less than 10% of the solid food samples. Pesticide residues were not detected in duplicate beverage samples. In solid food samples, the mean concentration of chlorpyrifos was 0.7 (SD 1.7) microg/kg, 1.8 (2.1) for malathion, and 0.2 (0.6) for p,p'-DDE. The detection rate and mean concentration of chlorpyrifos, malathion, and p,p'-DDE varied by a factor of 2-3 among sampling cycles and significantly according to results from several statistical analyses. Co-occurrence of chlorpyrifos and malathion in solid food samples was found relatively frequently and also varied with time. Pesticides were detected in food samples with greatest frequency in spring and summer months and with lowest frequency in winter months. These results support the hypothesis that 4-day average exposure to chlorpyrifos and malathion varies over time for this population mean and for individual members of the population and that correlation between exposures to these two organophosphate pesticides can occur. The measurements of pesticide levels in duplicate plate samples presented here can be used to evaluate and set parameters for dietary exposure models.

Baltimore↗

Air quality and pediatric emergency room visits for asthma in Atlanta, Georgia, USA.

Pediatric emergency room visits for asthma were studied in relation to air quality indices in a spatio-temporal investigation of approximately 130,000 visits (approximately 6,000 for asthma) to the major emergency care centers in Atlanta, Georgia, during the summers of 1993-1995. Generalized estimating equations, logistic regression, and Bayesian models were fitted to the data. In logistic regression models comparing estimated exposures of asthma cases with those of the nonasthma patients, controlling for temporal and demographic covariates and using residential zip code to link patients to spatially resolved ozone levels, the estimated relative risk per 20 parts per billion (ppb) increase in the maximum 8-hour ozone level was 1.04 (p < 0.05). The estimated relative risk for particulate matter less than or equal to 10 microm in aerodynamic diameter (PM10) was 1.04 per 15 microg/m3 (p < 0.05). Exposure-response trends (p < 0.01) were observed for ozone (>100 ppb vs. <50 ppb: odds ratio = 1.23, p = 0.003) and PM10 (>60 microg/m3 vs. <20 microg/m3: odds ratio = 1.26, p = 0.004). In models with ozone and PM10, both terms became nonsignificant because of collinearity of the variables (r= 0.75). The other analytical approaches yielded consistent findings. This study supports accumulating evidence regarding the relation of air pollution to childhood asthma exacerbation.

Adolescent↗

Measurement variability associated with KXRF bone lead measurement in young adults.

In vivo bone lead measurement using K X-ray fluorescence (KXRF) has been used to estimate long-term lead exposure, especially in adults. Relatively few studies have been conducted on young subjects with this technique. To explore the measurement variability of KXRF bone lead measurements in young subjects, the tibiae of two male cadavers from Boston, Massachusetts, 17 and 20 years of age, were obtained for repeated bone lead measurements. Bone lead concentrations were measured using a grid of nine locations, 1 cm apart, centered at the midpoint of the tibia. Each location was sampled using five 60-min measurements. Measured concentrations ranged from < 0 to 11.8 microg Pb/g bone mineral across a tibia with mean concentrations for the midpoint locations of 0.8 microg Pb/g bone mineral SD = 2.5 and 2.0 microg Pb/g bone mineral (SD = 1.9) for the left and right legs of the younger subject and 3.6 microg Pb/g bone mineral (SD = 2.6) and 6.0 microg Pb/g bone mineral (SD = 3.3) for the left and right legs of the older subject. Although bone lead concentrations did not vary significantly by measurement location in an individual leg, reported measurement uncertainty increased significantly at locations that were 1 cm from the center of the tibia horizontally (p < 0.0001). Symmetry in bone lead concentration between legs was observed for the 17-year-old subject. Potential asymmetry between the left and right legs was suggested for the 20-year-old subject (p = 0.06). These data describe the degree of variability that may be associated with bone lead measurements of young subjects with low bone lead concentrations using a standard spot-source KXRF instrument. Because of the importance of conducting additional research on adolescent lead toxicity, further improvements to the precision of KXRF measurement are needed.

Adolescent↗

Longitudinal investigation of exposure to arsenic, cadmium, and lead in drinking water.

Arsenic, cadmium, and lead have been associated with various forms of cancer, nephrotoxicity, central nervous system effects, and cardiovascular disease in humans. Drinking water is a well-recognized pathway of exposure to these metals. To improve understanding of the temporal dimension of exposure to As, Cd, and Pb in drinking water, we obtained 381 samples of tap and/or tap/filtered water and self-reported rates of drinking water consumption from 73 members of a stratified random sample in Maryland. Data were collected at approximately 2-month intervals from September 1995 through September 1996. Concentrations of As (range < 0.2-13.8 microg/L) and Pb (< 0.1-13.4 microg/L) were within the ranges reported for the United States, as were the rates of drinking water consumption (median < 0.1-4.1 L/day). Cd was present at a detectable level in only 8.1% of the water samples. Mean log-transformed concentrations and exposures for As and Pb varied significantly among sampling cycles and among respondents, as did rates of drinking water consumption, according to a generalized linear model that accounted for potential correlation among repeated measures from the same respondent. We used the intraclass correlation coefficient of reliability to attribute the total variance observed for each exposure metric to between-person and within-person variability. Between-person variability was estimated to account for 67, 81, and 55% of the total variance in drinking water consumption, As exposure (micrograms per day), and Pb exposure (micrograms per day), respectively. We discuss these results with respect to their implications for future exposure assessment research, quantitative risk assessment, and environmental epidemiology.

Arsenic↗

Neurological effects of environmental exposure to arsenic in dust and soil among humans.

Persons living in a small town in Georgia, USA, were studied because of known environmental exposure to arsenic-containing dust. To assess the effects of this exposure on the nervous system, a cross-sectional epidemiological study was performed. The health outcome assessments of the study were based on a priori selected clinical examination results and quantitative electrophysiologic and behavioral outcome measures. Because the primary goal was to identify cases of peripheral neuropathy, a clinically relevant case definition, based on results of these outcomes was created. Historical exposure reconstructions were performed on a subset of the exposed subjects for whom such information was available. Of the 238 persons enrolled in the study, 133 were classified as non-exposed (i.e., did not reside in the area of known exposure) and 105 were classified as exposed (i.e., did reside in the area of known exposure). Following exclusions of persons with occupational exposure to neurotoxicants, pre-existing conditions associated with peripheral nerve impairment, or age below 18 years, 118 unexposed subjects and 85 exposed subjects were available for inclusion in the analyses of peripheral nerve outcomes. A total of 4 (3.4%) of the unexposed subjects and 13 (15.3%) of the exposed subjects met the case definitions for peripheral neuropathy (OR=5.1; p=0.004). Comparison of three exposure groups (none, low, high) did not yield statistically significant differences. Statistically significant exposure group differences were observed on quantitative tests of standing steadiness, vibrotactile threshold and tremor intensity but not for nerve conduction measures. These results demonstrate a strong association between community arsenic containing dust exposure and peripheral neuropathy among participants in this investigation.

Adult↗

Relations between individual and neighborhood-based measures of socioeconomic position and bone lead concentrations among community-exposed men: the Normative Aging Study.

To examine the association between lead exposure and both individual and geographic area indicators of socioeconomic position, the authors measured tibia lead concentration, a biomarker of cumulative lead exposure, using K x-ray fluorescence in a cross-sectional survey of 538 white males aged 50-92 years who were healthy when enrolled in the Normative Aging Study (Boston, Massachusetts) in the 1960s. Data on individual risk factors, education, occupation, and income were collected by questionnaire. Using subjects' residential addresses at the time of the tibia lead measurements, the authors obtained geographic area-specific measures of education, social class, and poverty by linking records to 1990 US Census block group data. In multivariate linear regression analysis controlling for age and cumulative smoking, tibia lead concentrations were 10.39 microg/g (95% confidence interval (CI) 7.80-12.97) higher in men who did not graduate from high school than in men with > or =4 years of college. Among the former men (non-high school graduates), living in an undereducated area was associated with a 9.28 microg/g (95% CI 1.59-16.97) increase in tibia lead level compared with living in a non-undereducated area; among the latter men (college graduates), no difference existed by residential area education (beta = 0.72, 95% CI -5.35 to 6.78). The authors conclude that the influence of individual socioeconomic position on cumulative lead exposure is modified by geographic area conditions.

Adult↗

Urine vanadium concentrations in workers overhauling an oil-fired boiler.

Since fuel oil ash contains vanadium (V), the measurement of urinary levels of V may provide a biological marker in workers exposed to fuel oil ash. The usefulness of urine V samples as a biological monitoring tool ultimately depends on determining the appropriate time of sampling relative to when exposure occurs. Twenty boilermakers were studied during the overhaul of a large oil-fired boiler. A total of 117 urine samples were collected, 65 start-of-shift (S-O-S) and 52 end-of-shift (E-O-S) samples. Air V exposures were estimated with personal sampling devices and work history diaries. Air V concentrations ranged from 0.36 to 32.19 micrograms V/m3, with a mean +/- SD of 19.1 +/- 10.7, and a median of 18.5. On the first day of work on the overhaul, the V urine levels at the E-O-S (mean +/- SD were 1.53 +/- 0.53, median was 1.52 mg V/g creatinine) were significantly higher than those at the S-O-S (0.87 +/- 0.32, median was 0.83), P = 0.004. However, the V concentrations of the S-O-S urine samples on the last Monday of the study were not significantly different from the S-O-S urine levels on the previous Saturday, a time interval of about 38 hr between the end of exposure and sample collection. The Spearman correlation coefficient (r) between the S-O-S urine V and the workplace concentration of V dust during the previous day was r = 0.35. In summary, the results suggest a rapid initial clearance of V (elevating the E-O-S V concentration on the first day of work relative to the S-O-S concentration), followed by a slow clearance that is not complete 38 hr after the end of exposure, as evidenced by the Monday morning urine V concentrations. The Spearman correlations suggest that the S-O-S urine is preferred to the E-O-S urine for across-shift biological monitoring of V exposure.

Adult↗

Validation of a self-administered lead exposure questionnaire among suburban teenagers.

Teenagers represent a unique population in which to evaluate lead exposure. A self-administered questionnaire was developed to evaluate the current and historic lead exposures of teenagers. This work evaluates the exposure questionnaire for both its ability to predict lead exposure and the accuracy of the teenage respondents. Subjects received the survey at school and were instructed to get assistance from their parents in questionnaire completion. Environmental samples (dust, soil, and water) were collected from 30 suburban Boston homes to evaluate the questionnaire's predictiveness. To evaluate the accuracy of subjects' responses, independent information about housing was obtained. The questionnaire was effective in identifying predictors of dust and soil lead levels, but not for water lead levels. Fine dust lead loading (< 150 microns) varied significantly among the six housing age categories (pre-1940, 1940-1949, 1950-1959, 1960-1969, 1970-1979, and > 1979) and traffic levels. Fine dust lead concentrations varied significantly with decade of housing construction. Mean soil lead levels varied significantly among housing age categories, traffic levels, and exterior construction materials. For the important predictors, there was excellent agreement between the teenagers' self-report and confirmatory information. For housing age categories, the observed agreement was 69%; for traffic level, the observed agreement was 88%. These results illustrate that questionnaires continue to be useful in evaluating home lead levels even in suburban homes and that teenagers are accurate respondents.

Adolescent↗

In vivo bone lead measurement in suburban teenagers.

OBJECTIVE: Bone represents a biologically active long-term storage site for lead, and bone lead data on teenagers are limited. Therefore, this study was designed to identify the distribution of bone lead in a teenage population and to explore the environmental and demographic factors associated with bone lead concentrations in young, nonoccupationally exposed subjects. DESIGN: A cross-sectional study of bone lead levels in high school students. PARTICIPANTS: A total of 168 students at a suburban Boston high school. Subjects (90 boys, 78 girls) ranged in age from 13.5 to 19 years and included 40% nonwhite minorities. Of the 168 subjects, 45 lived in homes constructed before 1960. None of the participants reported a history of lead poisoning. OUTCOME MEASURES: Tibial bone lead concentrations were measured in vivo for 60 minutes using K x-ray fluorescence. Lead exposure information was obtained by self-administered questionnaire. RESULTS: Point estimates of bone lead levels ranged from -7.15 to 14.23 microg lead/g bone mineral (microg/g), (mean, 4.0 microg/g; standard deviation, 4.4 microg/g). The reported measurement uncertainties accompanying each of the point estimates ranged from 2.56 to 9.01 microg/g (mean, 3.9 microg/g; standard deviation, 1.0 microg/g). Bone lead levels were not associated with the demographic factors of age, sex, or race. Additionally, current home conditions (housing age, traffic level) were not predictive of bone lead levels, even though these factors were predictive of in-home lead concentrations. CONCLUSIONS: These results demonstrate that although bone lead levels are measurable in this age group, the common predictors of blood and bone lead concentrations are not explanatory for bone lead levels.

Adolescent↗

Dietary exposures to selected metals and pesticides.

Average daily dietary exposures to 11 contaminants were estimated for approximately 120,000 U.S. adults by combining data on annual diet, as measured by a food frequency questionnaire, with contaminant residue data for table-ready foods that were collected as part of the annual U.S. Food and Drug Administration Total Diet Study. The contaminants included in the analysis were four heavy metals (arsenic, cadmium, lead, mercury), three organophosphate pesticides (chlorpyrifos, diazinon, malathion), and four organochlorine pesticides (dieldrin, p,p'-DDE, lindane, heptachlor epoxide). Dietary exposures to these contaminants were highly variable among individuals, spanning two to three orders of magnitude. Intraindividual exposures to the metals, organophosphates, and organochlorines were estimated to be strongly correlated; Pearson's correlation coefficients ranged from 0.28 for lindane:dieldrin to 0.84 for lead:mercury. For some of the compounds (e.g., arsenic and dieldrin), a substantial fraction of the population was estimated to have dietary intakes in excess of health-based standards established by the EPA. Before use for risk assessment or epidemiologic purposes, however, the validity of the exposure estimates must be evaluated by comparison with biological indicators of chronic exposure. Because of their low detection rate in table-ready foods, the estimated distributions of exposures for dieldrin, p,p'-DDE, heptachlor epoxide, lindane, diazinon, and chlorpyrifos were found to be sensitive to assumed values for nondetect samples. Reliable estimates of the population distribution of dietary exposures to most other contaminants cannot be made currently, due to their low rate of detection in table-ready foods. Monitoring programs that use more sensitive study designs and population-based assessments for other subpopulations should be a priority for future research.

Adult↗

Measurement of organic acids, aldehydes, and ketones in residential environments and their relation to ozone.

Ozone and several polar volatile organic compounds (VOCs) including organic acids and carbonyls (aldehydes and ketones) were measured over an approximately 24 hour period in four residences during the winter of 1993 and in nine residences during the summer of 1993. All residences were in the greater Boston, Massachusetts area. The relation of the polar VOCs to the ozone concentration was examined. Indoor carbonyl concentrations were similar between the summer and winter, with the total mean winter concentration being 31.7 ppb and the total mean summer concentration being 36.6 ppb. However, the average air exchange rate was 0.9 hr-1 during the winter and 2.6 hr-1 during the summer. Therefore, the estimated carbonyl emission rates were significantly higher during the summer. Indoor organic acid concentrations were about twice as high during the summer as during the winter. For formic acid, the indoor winter mean was 9.8 ppb, and the summer indoor mean was 17.8 ppb. For acetic acid, the indoor winter mean was 15.5 ppb, and the summer indoor mean was 28.7 ppb. The concentrations of the polar VOCs were found to be significantly correlated with one another. Also, the emission rates of the polar VOCs were found to be correlated with both the environmental variables such as temperature and relative humidity and the ozone removal rate; however, it was difficult to apportion the relative effects of the environmental variables and the ozone removal.

Air Pollutants↗

Validation of K-XRF bone lead measurement in young adults.

K-X-ray fluorescence (K-XRF) is a useful tool for assessing environmental exposure to lead in occupationally exposed individuals and older adults. This study explores the possibility of using this technique on young adults with low environmental lead exposure. Twenty-three college students, aged 18-21 years, were recruited for 2 hr of bone lead measurement. Bone lead measurements were taken from the mid-shaft tibia for periods of 30 or 60 min. In the analysis, 30-min measurements were combined so that each subject had the equivalent of two 60-min measurements. The average concentration of two bone lead measurements in this population ranged from -1.5 to 8.2 micrograms Pb/g bone mineral, with a mean of 3.0 micrograms Pb/g bone mineral. In a one sample t-test, this mean was significantly different from 0 (p < 0.0001). A linear trend with age was detected despite the small age range of our population. By doubling the sampling time, the reported measurement uncertainty decreased by a factor of 1.5, resulting in uncertainty estimates below the mean bone lead estimates. Power calculations using the observed variance estimates suggest that with 80% power, differences in bone lead concentration of 2-3 micrograms Pb/g bone mineral can be identified in groups of 100 or smaller. Due to the large within-person variation in young adults, K-XRF may not yet be a useful diagnostic tool for individual subjects, but it may be of great use to environmental scientists trying to characterize long-term lead exposure and dose in the general population or specific subpopulations.

Adolescent↗

Personal exposure to nitrogen dioxide in the Los Angeles Basin.

A large scale study of human exposure to nitrogen dioxide (NO2) was conducted in the Los Angeles Basin, the only metropolitan area in the United States that exceeds the NO2 NAAQS. Data are available for a population representative sample of 482 households and 682 individuals. Personal exposures, as well as indoor and outdoor home levels, were monitored using passive time-integrating filter badges. Monitoring extended over a one-year period (May 1987 to May 1988), with each individual providing two consecutive days of data. Information was also collected on activity patterns, household and personal characteristics, and spatial and temporal variables. This paper describes the study design, summarizes the sample characteristics and representativeness, and presents the distribution of personal, indoor, and outdoor NO2 concentrations recorded by the monitors. Over the entire sample, median personal and outdoor levels were 35 ppb; median indoor levels were 24 ppb. Personal exposures for those in homes with gas ranges with pilot lights average 10 ppb greater than those with electric ranges, and 4 ppb greater than those with gas ranges without pilot lights. Forty percent of the variation in indoor concentrations is explained by outdoor levels; 59 percent of the variation in personal exposures is explained by indoor levels; and 48 percent of the variation in personal exposures is explained by outdoor levels.

Adolescent↗

The effect of neglecting correlations when propagating uncertainty and estimating the population distribution of risk.

Interest in examining both the uncertainty and variability in environmental health risk assessments has led to increased use of methods for propagating uncertainty. While a variety of approaches have been described, the advent of both powerful personal computers and commercially available simulation software have led to increased use of Monte Carlo simulation. Although most analysts and regulators are encouraged by these developments, some are concerned that Monte Carlo analysis is being applied uncritically. The validity of any analysis is contingent on the validity of the inputs to the analysis. In the propagation of uncertainty or variability, it is essential that the statistical distribution of input variables are properly specified. Furthermore, any dependencies among the input variables must be considered in the analysis. In light of the potential difficulty in specifying dependencies among input variables, it is useful to consider whether there exist rules of thumb as to when correlations can be safely ignored (i.e., when little overall precision is gained by an additional effort to improve upon an estimation of correlation). We make use of well-known error propagation formulas to develop expressions intended to aid the analyst in situations wherein normally and lognormally distributed variables are linearly correlated.

Analysis of Variance↗

Probabilistic connotations of carcinogen hazard classifications: analysis of survey data for anchoring effects.

A study was undertaken to test for anchoring effects when numerical probabilities were elicited for carcinogen hazard designations. Subjects were asked to assign probabilities to both probable and possible. The sequence was randomly varied so that half of the subjects evaluated probable first and half evaluated possible first. While there was no consensus on the numerical probabilistic meanings assigned to these verbal expressions, in general, probable was assigned a higher probability than possible and there were specific values that were assigned frequently, indicating some consistency in interpretation. There appeared to be a fairly constant scaling factor between the probabilities assigned to the designations. Anchoring was manifested in two ways: a smaller difference between the designations when they were evaluated in sequence than when they were evaluated in isolation, and assignment of readily accessible "benchmark" values such as 50% and 75%.

Carcinogens↗