Krista L.Y. Christensen

Population variability of phthalate metabolites and bisphenol A concentrations in spot urine samples versus 24- or 48-h collections.

Human exposure to phthalates and bisphenol A (BPA) can be assessed through urinary biomonitoring, but methods to infer daily intakes assume that spot sample concentrations are comparable to daily average concentrations. We evaluate this assumption using human biomonitoring data from Germany and the United States (US). The German data comprised three regional studies with spot samples and one with full-day samples analyzed for phthalate metabolites. The US data included: a study on DEHP metabolites and BPA involving eight persons supplying all urine voids (from which 24-h samples were constructed) for seven consecutive days; NHANES spot sample data on DEHP metabolites and BPA; and a regional study of children with 48-h samples analyzed for BPA. In the German data, measures of central tendency differed, but spot and 24-h samples showed generally comparable variance including 95th percentiles and maxima equidistant from central tendency measures. In contrast, the US adult data from the eight-person study showed similar central tendencies for phthalate metabolites and BPA, but generally greater variability for the spot samples, including higher 95th percentiles and maxima. When comparing childrens BPA concentrations in NHANES spot and 48-h samples, distributions showed similar central tendency and variability. Overall, spot urinary concentrations of DEHP metabolites and BPA have variability roughly comparable with corresponding 24-h average concentrations obtained from a comparable population, suggesting that spot samples can be used to characterize population distributions of intakes. However, the analysis also suggests that caution should be exercised when interpreting the high end of spot sample data sets.

Metals in blood and urine, and thyroid function among adults in the United States 2007–2008

The thyroid is integral to regulation of development and metabolism. Certain metals have been shown to affect thyroid function in occupationally exposed persons, but few studies have been conducted in the general population. This study evaluates the association between biomarkers of metal exposure and thyroid hormones in the US population. Analyses included adults participating in the 2007-2008 National Health and Nutrition Examination Survey, with no history of thyroid disease or use of thyroid medications, and with data on metals in blood (lead, cadmium and mercury) and urine (lead, cadmium, mercury, barium, cobalt, cesium, molybdenum, antimony, thallium, tungsten and uranium), and thyroid hormones (TSH, free and total T3 and T4) in serum (N=1587). Multivariate linear regression was used to model the association between thyroid hormone levels, and metals in either urine (creatinine-adjusted) or blood. Metal concentrations were considered as both continuous and categorical variables. Models were adjusted for: age, sex, race, BMI, serum lipids, serum cotinine, pregnancy and menopausal status, and use of selected medications. Few participants (<5%) had free T3, free T4, or TSH levels outside the reference range. However, 9.2% (SE=1.2%) had low T3 and 9.4% (SE=1.1%) had low T4. Metals were detected in nearly all blood and urine samples, with the highest levels seen for urinary molybdenum (median 42.5μg/L). When including all blood metals, mercury was associated with decreases in T3 and T4, while cadmium was associated with decreased TSH. Urinary cadmium was associated with increases in both T3 and T4 (models including all metals measured in urine). Urinary thallium and barium were associated with decreased T4 (both) and T3 (barium). For TSH, cesium was associated with decreased, and tungsten with increased levels. Given the high prevalence of exposure to metals, associations of the size reported here could indicate an appreciable contribution of metals exposure to the prevalence of thyroid disorders. These findings indicate the importance of further research to further examine these relationships.

The contribution of diet to total bisphenol A body burden in humans: results of a 48 hour fasting study.

Human biomonitoring studies measuring bisphenol A (BPA) in urine have shown widespread exposure in the general population. Diet is thought to be a major route of exposure. We studied urinary BPA patterns in five individuals over a 48-h period of fasting (bottled water only). Personal activity patterns were recorded with a diary to investigate non-dietary routes of exposure. All urine void events during the fast were collected, as well as events before and after the fast. The pattern of BPA concentrations was similar for all participants: they rose near the beginning of the fast (after the pre-fast meal), declined over the next 24h, fluctuated at lower levels during the second day, and then rose after the post-fast meal. Concentrations (~2 μg/g creatine) and calculated BPA intakes (~0.03 μg/kg-day) in these individuals during the first 24h were consistent with general population exposures. For the second 24h, concentrations and intakes declined by about two-thirds. One of the individuals had an extraordinary pre-fast exposure event with concentrations rising as high as 98 μg/g creatine but declining to <5 μg/g creatine by day 2. Given patterns found in day 1 and the subsequent decline to lower levels in day 2, we hypothesize that BPA exposures in these individuals were diet-driven. No events in the diary (use of personal care products, e.g.) appear associated with exposures. On day 2, non-dietary sources may still be present, such as from dust. Another hypothesis is that small reservoirs of BPA from past exposures are released from storage (lipid reservoirs, e.g.) and excreted.

A methodological approach to assessing the health impact of environmental chemical mixtures: PCBs and hypertension in the National Health and Nutrition Examination Survey.

We describe an approach to examine the association between exposure to chemical mixtures and a health outcome, using as our case study polychlorinated biphenyls (PCBs) and hypertension. The association between serum PCB and hypertension among participants in the 1999–2004 National Health and Nutrition Examination Survey was examined. First, unconditional multivariate logistic regression was used to estimate odds ratios and associated 95% confidence intervals. Next, correlation and multicollinearity among PCB congeners was evaluated, and clustering analyses performed to determine groups of related congeners. Finally, a weighted sum was constructed to represent the relative importance of each congener in relation to hypertension risk. PCB serum concentrations varied by demographic characteristics, and were on average higher among those with hypertension. Logistic regression results showed mixed findings by congener and class. Further analyses identified groupings of correlated PCBs. Using a weighted sum approach to equalize different ranges and potencies, PCBs 66, 101, 118, 128 and 187 were significantly associated with increased risk of hypertension. Epidemiologic data were used to demonstrate an approach to evaluating the association between a complex environmental exposure and health outcome. The complexity of analyzing a large number of related exposures, where each may have different potency and range, are addressed in the context of the association between hypertension risk and exposure to PCBs.

The Use of Epidemiology in Risk Assessment: Challenges and Opportunities

ABSTRACT The assessment of risk from environmental and occupational exposures incorporates and synthesizes data from a variety of scientific disciplines including toxicology and epidemiology. Epidemiological data have offered valuable contributions to the identification of human health hazards, estimation of human exposures, quantification of the exposure–response relation, and characterization of risks to specific target populations including sensitive populations. As with any scientific discipline, there are some uncertainties inherent in these data; however, the best human health risk assessments utilize all available information, characterizing strengths and limitations as appropriate. Human health risk assessors evaluating environmental and occupational exposures have raised concerns about the validity of using epidemiological data for risk assessment due to actual or perceived study limitations. This article highlights three concerns commonly raised during the development of human health risk assessments of environmental and occupational exposures: (a) error in the measurement of exposure, (b) potential confounding, and (c) the interpretation of non-linear or non-monotonic exposure–response data. These issues are often the content of scientific disagreement and debate among the human health risk assessment community, and we explore how these concerns may be contextualized, addressed, and often ameliorated.

Localized pleural thickening: Smoking and exposure to Libby vermiculite

There is limited research on the combined effects of smoking and asbestos exposure on risk of localized pleural thickening (LPT). This analysis uses data from the Marysville cohort of workers occupationally exposed to Libby amphibole asbestos (LAA). Workers were interviewed to obtain work and health history, including ever/never smoking and chest X-rays. Cumulative exposure estimates were developed on the basis of fiber measurements from the plant and work history. Benchmark concentration (BMC) methodology was used to evaluate the exposure–response relationship for exposure to LAA and a 10% increased risk of LPT, considering potential confounders and statistical model forms. There were 12 LPT cases among 118 workers in the selected study population. The mean exposure was 0.42 (SD=0.77) fibers/cc-year, and the prevalence of smoking history was 75.0% among cases and 51.9% among non-cases. When controlling for LAA exposure, smoking history was of borderline statistical significance (P-value=0.099), and its inclusion improved model fit, as measured by Akaikes Information Criterion. A comparison of BMC estimates was made to gauge the potential effect of smoking status. The BMC was 0.36 fibers/cc-year, overall. The BMC for non-smokers was approximately three times as high (1.02 fibers/cc-year) as that for the full cohort, whereas the BMC for smokers was about 1/2 that of the full cohort (0.17 fibers/cc-year).

Authors' response: A systematic review of the association between pleural plaques and changes in lung function.

We welcome the opportunity to respond to Goodman et al ,1 and to correct their misperceptions about our paper.2 As noted in their letter, Kerper et al 3 also recently analysed lung function decrements associated with pleural plaques. While the methodological details of our publications differed somewhat, the identified literature and the conclusions regarding magnitude of effect on lung function were well aligned. We found statistically significant 2–4% decrements in lung function in people exposed to asbestos with pleural plaques relative to asbestos-exposed people without abnormalities. Kerper et al 3 reported 3–5% decrements. It is not clear why Kerper et al 3 chose to ignore differences in study size: all studies were considered equally in their analysis, despite sample sizes ranging from tens to thousands, and a summary estimate was not calculated. With respect to the specific points raised, …