David Svendsgaard

Neurobehavioral deficits after low level lead exposure in neonates: the Mexico City pilot study.

Gestation age and ability of the baby to self-quiet and to be consoled during the first 30 days of life decrease when mothers 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.

Testicular effects of dinoseb in rats

Diets containing the herbicide dinoseb (2-sec- butyl 4,6-dinitrophenol) were fed to adult male Sherman rats for 11 weeks. One-half the survivors were killed for terminal studies during the eleventh week and the remainder bred to untreated females during posttreatment, and then killed for terminal studies. Interim sacrifices were made in groups fed 0 and 300 ppm. In rats fed 300 ppm, differential classification of spermatozoa from the cauda epididymidis indicated 90% of the cells were atypical by 20 days of treatment. By 30 days, bizarre and amorphous forms were observed and epididymal sperm counts were decreased. Histologic changes in the testes included abnormal spermatozoa and spermatids and multinucleated spermatogenic cells at 20 and 30 days and severe damage to spermatogenic cells by 50 days. Dietary levels of 225 and 300 ppm produced marked oligospermia and extensive loss of spermatogenic cells in rats fed dinoseb for 11 weeks. Evidence of necrotic spermatogenic cells was seen in some tubules, and in many tubules, only Sertoli cells remained. Reproductive failure occurred at 225 and 300 ppm, although mating behavior and libido were unaffected. There was little or no remission of these effects during the 16-week post-treatment period. Decreased epididymal sperm counts, atypical epididymal spermatozoa, and minimal testicular changes were seen in rats fed 150 ppm, but reproduction was unaffected and the anomalies were reversible. No effects were detected in animals fed 75 ppm.

The Influence of Declining Air Lead Levels on Blood Lead–Air Lead Slope Factors in Children

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. Citation: Richmond-Bryant J, Meng Q, Davis A, Cohen J, Lu SE, Svendsgaard D, Brown JS, Tuttle L, Hubbard H, Rice J, Kirrane E, Vinikoor-Imler LC, Kotchmar D, Hines EP, Ross M. 2014. The Influence of declining air lead levels on blood lead–air lead slope factors in children. Environ Health Perspect 122:754–760; http://dx.doi.org/10.1289/ehp.1307072

A multi-level model of blood lead as a function of air lead

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.

Contribution of Particle-Size-Fractionated Airborne Lead to Blood Lead during the National Health and Nutrition Examination Survey, 1999–2008

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.

Analysis of the concentration–respiratory response among asthmatics following controlled short-term exposures to sulfur dioxide

Some of the most compelling evidence of sulfur dioxide (SO2)-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 SO2. Although it is clear from these investigations that exposure to SO2 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 SO2 and measures of bronchoconstriction using individual subject lung function response data. In reviewing studies of asthmatics exposed to SO2 during 5- to 10-min periods of elevated ventilation, we observed clear and consistent evidence of an increase in the bronchoconstrictive response to SO2 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 SO2-induced respiratory effects at relatively high exposure concentrations are also more likely than nonresponders to experience similar effects after exposure to lower SO2 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 SO2 concentration and various measures of respiratory morbidity in the general population.

Quantitative methods for cross-species mapping (CSM).

Cross-species extrapolation will be defined as prediction from one species to another without empirical vetification. Cross-species mapping (CSM) is the same except empirical vetification is performed. CSM may be viewed as validation of methods for extrapolation. Algorithms for CSM may originate from theory, from empirical observations or a combination of the two. Regardless of their origins, CSM algorithms must be explicated and confidence intervals given around their predictions. This paper offers a quantitative method for constructing CSM equations which is useful in evaluation of the CSM and as an aid in the design of new experiments in CSM and extrapolation. The method requires fitting mathematical models for the physiological or behavioral phenomena to be mapped across species. A CSM equation can then be derived from the models in each species and approximate confidence limits may be obtained for predictions from the equation. The method is useful even when the models in the two species differ in form, implying differences in physiology or behavioral principles between species. The method proposed has a number of remaining uncertainties and possible problems.

Long-term accumulation of hexachlorobenzene in adipose tissue of parent and filial rats.

The concentrations of hexachlorobenzene (HCB) in adipose tissue were similar for F0 and F1b generations in rats fed 20 ppm HCB until 45 weeks of age. Nulliparous females receiving treatment equivalent to the HCB-treated F0 generation rapidly accumulated HCB in their fat and, by 13 weeks of age, the residue values coalesced with values in 13-week-old F1a females which had received additional HCB via the placenta and milk. Between 13 and 30 weeks of age, steady-state storage was approached and no significant increase in HCB concentrations occurred through 65 weeks of age. Postlactation dams, that nursed average size second litters, had considerably lower concentrations of HCB in their fat than dams weaning no pups, suggesting substantial redistribution and/or elimination of maternal stores during lactation.

Effect measure modification of blood lead–air lead slope factors

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.