The objective of this work is to examine associations between blood lead (PbB) and air lead (PbA) in particulate matter measured at different size cuts by use of PbB concentrations from the National Health and Nutrition Examination Survey and PbA concentrations from the U.S. Environmental Protection Agency for 1999-2008. Three size fractions of particle-bound PbA (TSP, PM10, and PM2.5) data with different averaging times (current and past 90-day average) were utilized. A multilevel linear mixed effect model was used to characterize the PbB-PbA relationship. At 0.15 μg/m(3), a unit decrease in PbA in PM10 was significantly associated with a decrease in PbB of 0.3-2.2 μg/dL across age groups and averaging times. For PbA in PM2.5 and TSP, slopes were generally positive but not significant. PbB levels were more sensitive to the change in PbA concentrations for children (1-5 and 6-11 years) and older adults (≥ 60 years) than teenagers (12-19 years) and adults (20-59 years). For the years following the phase-out of Pb in gasoline and a resulting upward shift in the PbA particle size distribution, PbA in PM10 was a statistically significant predictor of PbB. The results also suggest that age could affect the PbB-PbA association, with children having higher sensitivity than adults.

BACKGROUND:It is difficult to discern the proportion of blood lead (PbB) attributable to ambient air lead (PbA), given the multitude of lead (Pb) sources and pathways of exposure. The PbB-PbA relationship has previously been evaluated across populations. This relationship was a central consideration in the 2008 review of the Pb national ambient air quality standards.OBJECTIVES:The objectives of this study were to evaluate the relationship between PbB and PbA concentrations among children nationwide for recent years and to compare the relationship with those obtained from other studies in the literature.METHODS:We merged participant-level data for PbB from the National Health and Nutrition Examination Survey (NHANES) III (1988-1994) and NHANES 9908 (1999-2008) with PbA data from the U.S. Environmental Protection Agency. We applied mixed-effects models, and we computed slope factor, d[PbB]/d[PbA] or the change in PbB per unit change in PbA, from the model results to assess the relationship between PbB and PbA.RESULTS:Comparing the NHANES regression results with those from the literature shows that slope factor increased with decreasing PbA among children 0-11 years of age.CONCLUSION:These findings suggest that a larger relative public health benefit may be derived among children from decreases in PbA at low PbA exposures. Simultaneous declines in Pb from other sources, changes in PbA sampling uncertainties over time largely related to changes in the size distribution of Pb-bearing particulate matter, and limitations regarding sampling size and exposure error may contribute to the variability in slope factor observed across peer-reviewed studies.

There is abundant literature finding that susceptibility factors, including race and ethnicity, age, and housing, directly influence blood lead levels. No study has explored how susceptibility factors influence the blood lead–air lead relationship nationally. The objective is to evaluate whether susceptibility factors act as effect measure modifiers on the blood lead–air lead relationship. Participant level blood lead data from the 1999 to 2008 National Health and Nutrition Examination Survey were merged with air lead data from the US Environmental Protection Agency. Linear mixed effects models were run with and without an air lead interaction term for age group, sex, housing age, or race/ethnicity to determine whether these factors are effect measure modifiers for all ages combined and for five age brackets. Age group and race/ethnicity were determined to be effect measure modifiers in the all-age model and for some age groups. Being a child (1–5, 6–11, and 12–19 years) or of Mexican-American ethnicity increased the effect estimate. Living in older housing (built before 1950) decreased the effect estimate for all models except for the 1–5-year group, where older housing was an effect measure modifier. These results are consistent with the peer-reviewed literature of time-activity patterns, ventilation, and toxicokinetics.

A Current Assessment of the Health Effects of Lead in ChildrenAbstract Number:2012 Ellen Kirrane*, Molini Patel, James Brown, Dennis Kotchmar, Lisa Vinikoor-Imler, Elizabeth Owens, Erin Hines, Jennifer Richmond-Bryant, David Svendsgaard, and Meredith Lassiter Ellen Kirrane* United States Environmental Protection Agency, United States, E-mail Address: [email protected] , Molini Patel United States Environmental Protection Agency, United States, E-mail Address: [email protected] , James Brown United States Environmental Protection Agency, United States, E-mail Address: [email protected] , Dennis Kotchmar United States Environmental Protection Agency, United States, E-mail Address: [email protected] , Lisa Vinikoor-Imler United States Environmental Protection Agency, United States, E-mail Address: [email protected] , Elizabeth Owens United States Environmental Protection Agency, United States, E-mail Address: [email protected] , Erin Hines United States Environmental Protection Agency, United States, E-mail Address: [email protected] , Jennifer Richmond-Bryant United States Environmental Protection Agency, United States, E-mail Address: [email protected] , David Svendsgaard United States Environmental Protection Agency, United States, E-mail Address: [email protected] , and Meredith Lassiter United States Environmental Protection Agency, United States, E-mail Address: [email protected] AbstractThe U.S. Environmental Protection Agency (EPA) recently released the Integrated Science Assessment (ISA) for Lead (Pb), an integrative synthesis of the scientific evidence most relevant to the review of the National Ambient Air Quality Standard for Pb. We present select findings from the ISA and summarize the evidence that is most pertinent for pediatricians and children's health professionals. Although emissions to the environment and blood Pb levels in the U.S. have declined over the last several decades, the potential for Pb exposure remains and its effects are observed at increasingly lower blood Pb concentrations. A large body of evidence indicates that cognitive function decrements are associated with multiple lifestages, time periods, and durations of Pb exposure during childhood and into adolescence. Although the independent effects of Pb exposure on cognition in children are well established, research to identify factors that may mitigate these effects is ongoing. Recent epidemiologic and animal studies find that Pb exposure can cause decreased attention and increased impulsivity and hyperactivity. Some neurodevelopmental effects may persist into adulthood. Pb exposure can also cause a delay in pubertal onset and is likely to contribute to the development of asthma and allergy. A small group of studies indicates that early life and/or long-term exposures to Pb beginning in childhood may be associated with diseases later in life. Because blood Pb levels reflect recent exposures and can also be influenced by Pb that is released from bone, there is uncertainty regarding the specific exposure circumstances that underlie the blood Pb levels and associations observed in epidemiologic studies. This uncertainty is lowest for cognitive effects in young children, which are documented to occur at the lowest blood Pb concentrations. The views expressed in this abstract are those of the authors and do not necessarily represent the views or policies of the U.S. EPA.

National and local declines in lead (Pb) in blood (PbB) over the past several years coincide with the decline in ambient air Pb (PbA) concentrations. The objective of this work is to evaluate how the relationship between PbB levels and PbA levels has changed following the phase out of leaded gasoline and tightened controls on industrial Pb emissions over the past 30 years among a national population sample. Participant-level data from the National Health and Nutrition Examination Survey (NHANES) were employed for two time periods (1988–1994 and 1999–2008), and the model was corrected for housing, demographic, socioeconomic, and other covariates present in NHANES. NHANES data for PbB and covariates were merged with PbA data from the U.S. Environmental Protection Agency. Linear mixed effects models (LMEs) were run to assess the relationship of PbB with PbA; sample weights were omitted, given biases encountered with the use of sample weights in LMEs. The 1988–1994 age-stratified results found that ln(PbB) was statistically significantly associated with ln(PbA) for all age groups. The consistent influence of PbA on PbB across age groups for the years 1988–1994 suggests a ubiquitous exposure unrelated to age of the sample population. The comparison of effect estimates for ln(PbA) shows a statistically significant effect estimate and ANOVA results for ln(PbB) for the 6- to 11-year and 12- to 19-year age groups during 1999–2008. The more recent finding suggests that PbA has less consistent influence on PbB compared with other factors.

Although positive associations between ambient NO2 concentrations and personal exposures have generally been found by exposure studies, the strength of the associations varied among studies. Differences in results could be related to differences in study design and in exposure factors. However, the effects of study design, exposure factors, and sampling and measurement errors on the strength of the personal-ambient associations have not been evaluated quantitatively in a systematic manner. A quantitative research synthesis was conducted to examine these issues based on peer-reviewed publications in the past 30 years. Factors affecting the strength of the personal-ambient associations across the studies were also examined with meta-regression. Ambient NO2 was found to be significantly associated with personal NO2 exposures, with estimates of 0.42, 0.16, and 0.72 for overall pooled, longitudinal and daily average correlation coefficients based on random-effects meta-analysis. This conclusion was robust after correction for publication bias with correlation coefficients of 0.37, 0.16 and 0.45. We found that season and some population characteristics, such as pre-existing disease, were significant factors affecting the strength of the personal-ambient associations. More meaningful and rigorous comparisons would be possible if greater detail were published on the study design (e.g. local and indoor sources, housing characteristics, etc.) and data quality (e.g., detection limits and percent of data above detection limits). Published by Elsevier Ltd.

Although particulate matter (PM), nitrogen dioxide (NO2) and carbon monoxide (CO) typically exist as part of a complex air pollution mixture, the evidence linking these pollutants to health effects is evaluated separately in the scientific and policy reviews of the National Ambient Air Quality Standards (NAAQS). The objective of this analysis was to use meta-regression methods to model effect estimates for several individual yet correlated NAAQS pollutants in an effort to identify factors that explain differences in the effect sizes across studies and across pollutants. We expected that our consideration of the evidence for several correlated pollutants in parallel could lead to insights regarding exposure to the pollutant mixture. We focused on studies of hospital admissions for congestive heart failure (CHF) and ischemic heart disease (IHD), which have played an important role in the evaluation of the scientific evidence communicated in the PM, NO2, and CO Integrated Science Assessments (ISAs). Of the studies evaluated, 11 CHF studies and 21 IHD studies met our inclusion requirements. The size of the risk estimates was explained by factors related to the pollution mixture, study methods, and monitoring network characteristics. Our findings suggest that additional analyses focusing on understanding differences in effect sizes across geographic areas with different pollution mixtures and monitor network designs may improve our understanding of the independent and combined effects of correlated pollutants.

Some of the most compelling evidence of sulfur dioxide (SO(2))-induced respiratory morbidity is derived from a large body of studies involving controlled short-term exposures among groups of asthmatic volunteers. These studies were extensively cited in the recently completed review of the primary National Ambient Air Quality Standards for SO(2). Although it is clear from these investigations that exposure to SO(2) may result in a significant increase in bronchoconstriction, there is uncertainty regarding the range of concentrations over which this respiratory response occurs. The objective of this study was to better characterize the concentration-response relationship between SO(2) and measures of bronchoconstriction using individual subject lung function response data. In reviewing studies of asthmatics exposed to SO(2) during 5- to 10-min periods of elevated ventilation, we observed clear and consistent evidence of an increase in the bronchoconstrictive response to SO(2) with increasing exposure concentrations between 0.2 and 1.0 ppm. In a subsequent analysis of individual subject data, it was found that those asthmatics experiencing SO(2)-induced respiratory effects at relatively high exposure concentrations are also more likely than nonresponders to experience similar effects after exposure to lower SO(2) concentrations (≤0.4 ppm). Although the clinical significance of these effects is unsettled, the findings provide additional support to epidemiologic evidence of an association between ambient SO(2) concentration and various measures of respiratory morbidity in the general population.

Studies examining the effects of low-level gestational methylmercury exposure from fish consumption on infant neurobehavioral outcomes in the offspring are limited and inconclusive. Our objective was to examine the effects of low-level gestational exposure to methylmercury on neurobehavioral outcomes in early infancy.We assessed neurobehavior of 344 infants at 5-weeks using the NICU Network Neurobehavioral Scale (NNNS). Gestational mercury exposure was measured as whole blood total mercury (WBTHg) in maternal and cord blood. We collected fish consumption information and estimated polyunsaturated fatty acid (PUFA) intake. We examined the association between gestational mercury exposure and NNNS scales using regression, adjusting for covariates.Geometric mean of maternal and cord WBTHg were 0.64 and 0.72 μg/L, respectively. Most mothers (84%) reported eating fish during pregnancy. Infants with higher prenatal mercury exposure showed increased asymmetric reflexes among girls (p = 0.04 for maternal WBTHg and p = 0.03 for cord WBTHg), less need for special handling during the assessment (p = 0.03 for cord WBTHg) and a trend of better attention (p = 0.054 for both maternal WBTHg and cord WBTHg). Similarly, infants born to mothers with higher fish consumption or estimated PUFA intake also had increased asymmetric reflexes and less need for special handling. In models simultaneously adjusted for WBTHg and fish consumption (or PUFA intake), the previously observed WBTHg effects were attenuated; and higher fish consumption (or PUFA intake) was significantly associated with less need for special handling.In a cohort with low level mercury exposure and reporting low fish consumption, we found minimal evidence of mercury associated detrimental effects on neurobehavioral outcomes during early infancy. Higher prenatal mercury exposure was associated with more frequent asymmetric reflexes in girls. In contrast, infants with higher prenatal mercury exposure and those whose mothers consumed more fish had better attention and needed less special handling, which likely reflect the beneficial nutritional effects of fish consumption.

Gestation age and ability of the baby to self-quiet and to be consoled during the first 30 days of life decrease when mother's blood lead levels rise from 36 weeks of pregnancy to birth of child. These effects appear to be independent of the absolute lead levels of mother and child (N=42). Since pre- and perinatal stress predicts higher maternal birth lead, further work could determine the relative contributions of undetected stress during pregnancy and elevated lead levels upon subsequent development. Several cases, not included in the statistical analyses, showed associations between cord leads greatly elevated over maternal leads and poor outcome.

Female Sprague-Dawlwy CD rats were fed 0, 60, 80, 100, 120 and 140 ppm hexachlorobenzene (HCB) continuously in the diet and 2 successive litters raised. These doses were selected to range from approximately the no observable effect level to lethality in suckling offspring of treated dams. In the F1a generation, the 21-day mortality was 9.2, 19.8, 30.0, 45.4, 93.1 and 92.6% in offspring of dams fed 0, 60, 80, 100, 120 and 140 ppm HCB, respectively. In the F1b generation, a similar mortality of 18.5, 21.5, 19.5, 45, 100 and 94.1% was observed at these 5 dose levels, respectively. The neonatal lethality observed was related to both maternal dose of HCB and the cumulative lactational exposure. Clinical signs of maternal toxicity were not observed and fertility and fecundity were unaffected. In the lungs of HCB treated dams, increased numbers of intraalveolar foamy histiocytes and hypertrophy and proliferation of the lining endothelial cells of pulmonary venules were observed. These microscopic findings of pulmonary effects of HCB confirmed previous findings of this laboratory.