Search

To establish primary National Ambient Air Quality Standards (NAAQS) for criteria air pollutants such as nitrogen dioxide (NO2), ozone (O3), and sulfur dioxide (SO2), US EPA relies in part on controlled human exposure studies. It has been suggested that evaluating average responses for all participants in these studies may not reflect the responses of sensitive participants in these studies. To evaluate this, we identified controlled exposure studies with multiple exposure concentrations or durations that provided individual-level lung function data. Based on individual lung function responses at specific exposure concentrations and the slope of individual concentration-response curves, we identified 12 participants out of a total of 208 participants in 12 studies who were potentially sensitive to O3, SO2, or sulfuric acid (H2SO4). We did not identify any participants sensitive to NO2. All of these participants were found to be potentially sensitive only at concentrations that were well above the NAAQS (SO2), above likely ambient concentrations (H2SO4), or at concentrations at which the study reported significant lung function effects for all participants (O3). Based on our analysis, average responses for all participants combined adequately reflect lung function responses for potentially sensitive study participants at concentrations in the range of the current NAAQS.

Adults and children differ in their susceptibility to the toxic effects of lead. Lead was therefore used as a case study to evaluate intraspecies differences by comparing the adult and child minimal Lowest Observed Adverse Effect Level (LOAEL) or the No Observed Adverse Effect Level (NOAEL), allowing an evaluation of the ten-fold intraspecies uncertainty factor (UF). The lead intakes (in µg/kg/d) necessary to achieve target blood lead (PbB) levels reflecting the minimal LOAEL or NOAEL were determined using biokinetic slope factors (BKSFs), which relate lead uptake to PbB levels. The analyses assumed chronic, low-level oral exposure to lead, and the response of a typical adult and child. Child analyses used a target geometric mean (GM) PbB of 4.6 µg/dL (95% of population

Observed blood lead levels for young children from several communities are compared with blood lead levels predicted for those communities using the USEPA's Integrated Exposure Uptake Biokinetic (IEUBK) Model. In contrast to the compari sons described elsewhere, the blood lead levels observed in the communities con sidered here are not well represented by the model's predictions. The model's predictions for Midvale, UT; Sandy, UT; Cincinnati, OH; and a recent data set for Palmerton, PA, show considerable deviation from observation both for the geometric mean blood lead level and the percent of blood lead levels above 10 µg/dL. Various adjustments in the model to consider play area soils, site specific geometric standard deviations and the time children spend away from their homes do not substantially improve the comparisons to observation. It is difficult to predict a priori the data sets for which the model will yield adequate predictions. This reduces the value of the model for use in communities where ...

This presentation describes the development of a prototype Monte Carlo module for the physiologically-based pharmacokinetic (PBPK) model for lead, created by Dr Ellen O'Flaherty. The module uses distributions for the following: exposure parameters (soil and dust concentrations, daily soil and ingestion rate, water lead concentration, water ingestion rate, air lead concentration, inhalation rate and dietary lead intake); absoption parameters; and key pharmacokinetic parameters (red blood binding capacity and half saturation concentration). Distributions can be specified as time-invariant or can change with age. Monte Carlo model predicted blood levels were calibrated to empirically measured blood lead levels for children living in Midvale, Utah (a milling/smelting community). The calibrated model was then evaluated using blood lead data from Palmerton, Pennsylvania (a town with a former smelter) and Sandy, Utah, (a town with a former smelter and slag piles). Our initial evaluation using distributions for exposure parameters showed that the model accurately predicted geometric (GM) blood lead levels of Palmerton and Sandy and slightly over predicted the GSD. Consideration of uncertainty in red blood cell parameters substantially inflated the GM. Future model development needs to address the correlation among parameters and the use of parameters for long-term exposure derived from short-term studies.

Gastrointestinal (GI) symptoms, the primary acute effect of the essential micronutrient copper, paradoxically occur at lower exposure levels than hepatotoxicity, the primary chronic effect. We developed a remedial action criterion (RAC) for copper to protect against GI symptoms, which primarily relate to the stomach copper concentration, and subside within an hour. Using Monte Carlo methods, we generated a distribution of RACs protective against GI symptoms for a 1 h exposure (hourly RACs) based on soil ingestion rate, volume of liquid and food in the stomach, and bioaccessibility. We then generated a distribution of daily RACs, selected as the minimum hourly RAC for each day over a year, constrained by total daily soil ingestion. Next, we identified a percentile of the distribution of daily RACs, and associated RAC, that would result in a high probability of having a minimal number of GI symptom episodes per year. Our analysis indicates that a copper concentration of 3600 mg/kg would result in a 95% probability of having fewer than five episodes of GI symptoms per year, for a child ingesting outdoor soil 180 days per year. Children residing near copper smelters are most likely to experience GI symptoms from ingestion of copper in soil.

Blood lead levels in children in the United States have declined through 1994, the date of the most recent National Health and Nutrition Examination Survey. In this investigation, the authors analyzed whether blood lead levels have changed since 1994 and quantified the magnitude of any change. The authors evaluated blood lead levels from 12 longitudinal data sets from 11 states and 1 city. Geometric mean blood lead levels declined between 4%/year and 14%/year in 8 of the data sets. No differences in decline rates were observed between data sets from states that had universal screening as a goal or that included repeat measures for an individual child and those data sets that did not. The authors' best estimate for these populations was a decline rate of 4-7%/year, which was comparable to the decline rate prior to 1994.