Richard Hornung

Abstract In the attempt to estimate the average concentration of a particular contaminant during some period of time, a certain proportion of the collected samples is often reported to be below the limit of detection. The statistical terminology for these results is known as censored data, i.e., nonzero values which cannot be measured but are known to be below some threshold. Samples taken over time are assumed to follow a lognormal distribution. Given this assumption, several techniques are presented for estimation of the average concentration from data containing nondetectable values. The techniques proposed include three methods of estimation with a left-censored lognormal distribution: a maximum likelihood statistical method and two methods involving the limit of detection. Each method is evaluated using computer simulation with respect to the bias associated with estimation of the mean and standard deviation. The maximum likelihood method was shown to produce unbiased estimates of both the mean and standard deviation under a variety of conditions. However, this method is somewhat complex and involves laborious calculations and use of tables. Two simpler alternatives involve the substitution of L/2 and a new proposal of L/2 for each nondetectable value, where L = the limit of detection. The new method was shown to provide more accurate estimation of the mean and standard deviation than the L/2 method when the data are not highly skewed. The L/2 method should be used when the data are highly skewed (geometric standard deviation [GSD] approximately 3.0 or greater)

Lead is a confirmed neurotoxin, but questions remain about lead-associated intellectual deficits at blood lead levels < 10 microg/dL and whether lower exposures are, for a given change in exposure, associated with greater deficits. The objective of this study was to examine the association of intelligence test scores and blood lead concentration, especially for children who had maximal measured blood lead levels < 10 microg/dL. We examined data collected from 1,333 children who participated in seven international population-based longitudinal cohort studies, followed from birth or infancy until 5-10 years of age. The full-scale IQ score was the primary outcome measure. The geometric mean blood lead concentration of the children peaked at 17.8 microg/dL and declined to 9.4 microg/dL by 5-7 years of age; 244 (18%) children had a maximal blood lead concentration < 10 microg/dL, and 103 (8%) had a maximal blood lead concentration < 7.5 microg/dL. After adjustment for covariates, we found an inverse relationship between blood lead concentration and IQ score. Using a log-linear model, we found a 6.9 IQ point decrement [95% confidence interval (CI), 4.2-9.4] associated with an increase in concurrent blood lead levels from 2.4 to 30 microg/dL. The estimated IQ point decrements associated with an increase in blood lead from 2.4 to 10 microg/dL, 10 to 20 microg/dL, and 20 to 30 microg/dL were 3.9 (95% CI, 2.4-5.3), 1.9 (95% CI, 1.2-2.6), and 1.1 (95% CI, 0.7-1.5), respectively. For a given increase in blood lead, the lead-associated intellectual decrement for children with a maximal blood lead level < 7.5 microg/dL was significantly greater than that observed for those with a maximal blood lead level > or = 7.5 microg/dL (p = 0.015). We conclude that environmental lead exposure in children who have maximal blood lead levels < 7.5 microg/dL is associated with intellectual deficits.

To assess quantitatively the association between benzene exposure and leukemia, we examined the mortality rate of a cohort with occupational exposure to benzene. Cumulative exposure for each cohort member was estimated from historical air-sampling data and, when no sampling data existed, from interpolation on the basis of existing data. The overall standardized mortality ratio (a measure of relative risk multiplied by 100) for leukemia was 337 (95 percent confidence interval, 154 to 641), and that for multiple myeloma was 409 (95 percent confidence interval, 110 to 1047). With stratification according to levels of cumulative exposure, the standardized mortality ratios for leukemia increased from 109 to 322, 1186, and 6637 with increases in cumulative benzene exposure from less than 40 parts per million-years (ppm-years), to 40 to 199, 200 to 399, and 400 or more, respectively. A cumulative benzene exposure of 400 ppm-years is equivalent to a mean annual exposure of 10 ppm over a 40-year working lifetime; 10 ppm is the currently enforceable standard in the United States for occupational exposure to benzene. To examine the shape of the exposure-response relation, we performed a conditional logistic-regression analysis, in which 10 controls were matched to each cohort member with leukemia. From this model, it can be calculated that protection from benzene-induced leukemia would increase exponentially with any reduction in the permissible exposure limit.

BACKGROUND: Lead exposure is a risk factor for cardiovascular disease mortality, but the number of deaths in the USA attributable to lead exposure is poorly defined. We aimed to quantify the relative contribution of environmental lead exposure to all-cause mortality, cardiovascular disease mortality, and ischaemic heart disease mortality. METHODS: Our study population comprised a nationally representative sample of adults aged 20 years or older who were enrolled in the Third National Health and Nutrition Examination Survey (NHANES-III) between 1988 and 1994 and followed up to Dec 31, 2011. Participants had completed a medical examination and home interview and had results for concentrations of lead in blood, cadmium in urine, and other relevant covariates. Individuals were linked with the National Death Index. This study presents extended follow-up of an earlier analysis. FINDINGS: We included 14 289 adults in our study. The geometric mean concentration of lead in blood was 2·71 μg/dL (geometric SE 1·31). 3632 (20%) participants had a concentration of lead in blood of at least 5 μg/dL (≥0·24 μmol/L). During median follow-up of 19·3 years (IQR 17·6-21·0), 4422 people died, 1801 (38%) from cardiovascular disease and 988 (22%) from ischaemic heart disease. An increase in the concentration of lead in blood from 1·0 μg/dL to 6·7 μg/dL (0·048 μmol/L to 0·324 μmol/L), which represents the tenth to 90th percentiles, was associated with all-cause mortality (hazard ratio 1·37, 95% CI 1·17-1·60), cardiovascular disease mortality (1·70, 1·30-2·22), and ischaemic heart disease mortality (2·08, 1·52-2·85). The population attributable fraction of the concentration of lead in blood for all-cause mortality was 18·0% (95% CI 10·9-26·1), which is equivalent to 412 000 deaths annually. Respective fractions were 28·7% (15·5-39·5) for cardiovascular disease mortality and 37·4% (23·4-48·6) for ischaemic heart disease mortality, which correspond to 256 000 deaths a year from cardiovascular disease and 185 000 deaths a year from ischaemic heart disease. INTERPRETATION: Low-level environmental lead exposure is an important, but largely overlooked, risk factor for cardiovascular disease mortality in the USA. A comprehensive strategy to prevent deaths from cardiovascular disease should include efforts to reduce lead exposure. FUNDING: The Artemis Fund and Simon Fraser University.

BACKGROUND: Prenatal exposure to bisphenol A (BPA) increases offspring aggression and diminishes differences in sexually dimorphic behaviors in rodents. OBJECTIVE: We examined the association between prenatal BPA exposure and behavior in 2-year-old children. METHODS: We used data from 249 mothers and their children in Cincinnati, Ohio (USA). Maternal urine was collected around 16 and 26 weeks of gestation and at birth. BPA concentrations were quantified using high-performance liquid chromatography-isotope-dilution tandem mass spectrometry. Child behavior was assessed at 2 years of age using the second edition of the Behavioral Assessment System for Children (BASC-2). The association between prenatal BPA concentrations and BASC-2 scores was analyzed using linear regression. RESULTS: Median BPA concentrations were 1.8 (16 weeks), 1.7 (26 weeks), and 1.3 (birth) ng/mL. Mean (+/- SD) BASC-2 externalizing and internalizing scores were 47.6 +/- 7.8 and 44.8 +/- 7.0, respectively. After adjustment for confounders, log(10)-transformed mean prenatal BPA concentrations were associated with externalizing scores, but only among females [beta = 6.0; 95% confidence interval (CI), 0.1-12.0]. Compared with 26-week and birth concentrations, BPA concentrations collected around 16 weeks were more strongly associated with externalizing scores among all children (beta = 2.9; 95% CI, 0.2-5.7), and this association was stronger in females than in males. Among all children, measurements collected at <or= 16 weeks showed a stronger association (beta = 5.1; 95% CI, 1.5-8.6) with externalizing scores than did measurements taken at 17-21 weeks (beta = 0.6; 95% CI, -2.9 to 4.1). CONCLUSIONS: These results suggest that prenatal BPA exposure may be associated with externalizing behaviors in 2-year-old children, especially among female children.