Monthly Archives: November 2013

PIERCE ( 13V525000 )

Dated: OCT 21, 2013 Pierce Manufacturing Inc. (Pierce) is recalling certain model year 2000-2009 Enforcer and 2000-2010 Dash, Lance, and Arrow XT vehicles manufactured October 1, 2000, through May 31, 2010. The trunnion…

Neuropsychological Motor Outcomes in Adults from Airborne Manganese Exposure

Background: The literature on manganese (Mn) is dominated by occupational exposures of adults exposed often to high levels without protection. Neuropsychological adverse health effects are similar to Parkinson’s Disease with psychomotor slowing, tremor, cognitive and mood disturbances. Environmental exposures have rarely been studied in adults. Our study in two air-Mn exposed towns in Ohio is the first adult study in the U.S. with measures of motor, cognitive and mood function. This presentation presents the motor findings of 186 adults from two exposed towns, Marietta (N=100) and East Liverpool (N=86), Ohio.
The objective of this study was to evaluate motor function and Mn exposures as estimated by U.S.EPA’s AERMOD dispersion model, which was calibrated with measured data from air monitors in both towns. Estimated annual air-Mn exposures were as high as 1.93 9μg/m3 in total suspended particles (TSP). Exposure estimates were consistent with the range of measured air-Mn in the communities where air modeling was conducted. A cumulative exposure index (cDEI) was calculated and compared to motor test function with effect sizes reported.

Method and Results: Participants were carefully selected within 2 air-miles downwind from the source in East Liverpool and at random within Marietta (residents with serious non-related illnesses were excluded). Questionnaires, psychomotor, cognitive and mood tests were administered and blood samples were collected. Comparing Marietta with East Liverpool, years education (14.6 vs. 13.7) were higher in Marietta and years of residence greater in East Liverpool (36.1vs. 41.1). Blood levels for Mn and other metals were within normal limits. Tests of psychomotor speed and grip strength were associated (p <.05) with the cDEI with large effect sizes for: WAIS-III Digit Symbol, Fingertapping, Dynamometer and approached significance for tactile function (Grooved Pegboard).
Conclusion: Findings in this epidemiologic study showed lower exposures to Mn than for occupational studies yet similar results suggest that long-term chronic exposures impact the residents, albeit to a lower degree. The exposure methodology employed here shows that a combination of modeling and ambient air sampling and sensitive neuropsychological testing can be used when source emission data may not be available.
Note: This abstract does not necessarily reflect EPA policy

Take What You Have And Do More

The needs of a good animal care and use program evolve over time, but fitting program-wide innovations into an existing institutional framework can be challenging. Management at the National Health and Environmental Effects Research Laboratory (NHEERL) of the US EPA was convinced of the importance of formalizing oversight of animal use post protocol approval and agreed to institute a Post Approval Monitoring (PAM) program – within existing infrastructure. This challenge was handled by expanding the role of the IACUC Coordinator to include PAM. As the PAM program became accepted in the labs, it demonstrated its utility by revealing a whole new need. Cumulative PAM visits indicated inconsistency in skill sets across the NHEERL Labs, with dated techniques and procedures appearing regularly. While PAM visits frequently resulted in on the spot training, management considered this suboptimal and approved construction of a revamped training program using expertise and resources already in house. A rodent training colony (animals most used in NHEERL) was formed by collecting unused sentinel and retired animals. The training staff was built by soliciting observed expertise: the Attending Veterinarian, animal care staff, and research staff all contribute to the training program on a volunteer basis. Targeted classes cover basic skills as well as specifically identified techniques. Additionally, to address inexperience and fears discovered during PAM visits, a subset of colony rats are habituated to handling using positive reinforcement and individuals are introduced to these animals to build skill and confidence before graduating to nonsocialized rats. The training program has been successful. Feedback has been positive, and investigators are actively requesting training. Rat-phobic individuals have learned to work with rats after previously being unable to touch them. The basic training has kept animal handling consistent across labs, making observation and health checks easier for the animal care staff. PAM visits have observed procedures across the labs showing increased consistency and more current practices, allowing PAM to move in new directions to be incorporated into future training. These successful, interrelated programs were accomplished by creatively using available resources, without increase in staff or budget.This abstract does not reflect EPA Policy.

Dose-Response and Efficacy of Spinal Manipulation for Chronic Low-Back Pain: A New Study

Chronic low-back pain is one of the most common and costly health complaints. It can be debilitating, and it remains a tough condition to diagnose, treat, and study. Spinal manipulative therapy is often used to treat a large portion of low-back pain in the United States, and is included in current clinical practice guidelines for treatment of this condition. Yet, recommendations for duration and frequency vary widely and there is no consensus on its efficacy.

Detection of pyrethroid pesticides and their environmental degradation products in duplicate diet samples

The abstract is for an oral presentation at the Asilomar Conference on Mass Spectrometry: Mass Spectrometry in Environmental Chemistry, Toxicology, and Health. It describes analytical method development and sample results for determination of pyrethroid pesticides and environmental degradation products in duplicate diet samples from the Ex-R study. Introduction: Pyrethroids have been found in individual foods (i.e., fruits, vegetables) and duplicate diet composites. Pyrethroids have low mammalian toxicity, but some may be carcinogenic. Pyrethroid analysis in composite samples requires multiple extractions and cleanups; concurrent detection of the degradation products has not been reported. As the degradants also serve as urinary biomarkers, their presence in food samples could lead to over-estimates of dietary exposure. As part of an exposure reconstruction (Ex-R) study, we developed a rapid analytical method for pyrethroids and degradation products in duplicate diet samples, and demonstrated the method on 782 food composites.
Methods: Fifty adult participants collected 48-hour duplicate diet samples for six days over a six-week monitoring period. Samples were collected during three consecutive time periods each sampling day. Samples were analyzed for seven pyrethroids including bifenthrin and permethrin, and six degradation products. A modified QuECHERS approach was used for extraction and clean-up followed by LC/MS/MS.
Results: Method validation demonstrated detection limits from 0.010 – 2.5 ppb. At least one pyrethroid was detected in 49.7% of the food samples, with trans-permethrin observed most frequently (21.7%). However, the degradation products were detected in only 2.6% of the samples. Additional method parameters and study results will be detailed.
Conclusions: We developed a fast, sensitive, and accurate analysis for several pyrethroids and degradation products in food composites. Pyrethroids were detected in nearly half of the duplicate diet samples from the Ex-R study. The low incidence of degradation products suggests detection in bio fluids is not likely to be due to direct dietary ingestion.
This abstract does not necessarily reflect EPA policy.

Toxicity testing in the 21st Century: Extrapolation from in vitro to in vivo using xenoestrogens as a model

Slides associated with the following abstract: Numerous sources contribute to widespread contamination of drinking water sources with both natural and synthetic estrogens, which is a concern for potential ecological and human health effects. In vitro screening assays are valuable tools for identifying mechanisms of toxicity but in vitro results cannot be directly extrapolated to in vivo exposures since most in vitro assays do not account for metabolism, distribution and excretion or other systemic toxicities. In this study, we highlight some of the limitations associated with using in vitro estrogen transcriptional activation assays for predicting in vivo action of xenoestrogens. In particular, we compared the ability to predict the uterine growth response (uterotrophic assay, UA) to estrogens, administered to the rat orally either individually or as mixtures, using an in vitro estrogen transcriptional activation (TA) assay (T47D-kbluc cell line). We demonstrated that a binary mixture of bisphenol-AF (BPAF) + Methoxychlor in the UA conforms to dose additive (DA) estrogenicity, whereas the degree of estrogenicity of this mixture is underestimated by the TA assay. In contrast, the TA assay responded to a binary mixture of benzylbutyl phthalate (BBP) + BPAF in a DA manner, whereas, the UA displayed no estrogenic response to this mixture. These data illustrate the limitations associated with making in vivo predictions based on in vitro assay data for compounds that are metabolically inactivated in vivo in the liver, gut or other tissues or activated by the liver in vivo. This information is critical for valid interpretation of in vitro screening assay results.

Nonmonotonic Dose-Response Curves and Endocrine-Disrupting Chemicals: Fact or Falderal?**

Nonmonotonic Dose-Response Curves and Endocrine-Disrupting Chemicals: Fact or Falderal?
The shape of the dose response curve in the low dose region has been debated since the 1940s, originally focusing on linear no threshold (LNT) versus threshold responses for cancer and noncancer effects. Recently, it has been claimed that endocrine
disrupters (EDCs), which act via high affinity, low capacity receptors, commonly induce adverse effects displaying Nonmonotonic Dose-Response Curves (NMDRCs) at low doses. Effects that would be missed in standard EDC screening and multigenerational testing protocols. Case studies of chemicals that disrupt reproductive development and function via the androgen and estrogen signaling pathways were reviewed, including in vitro and in vivo multigenerational studies for LNT, threshold and NMDRCs responses. In vivo studies selected included comprehensive, robust, well designed studies that administered the chemical via a relevant route of exposure over a broad dose response range, including low doses. The chemicals include ethinyl estradiol, estradiol, genistein, bisphenol A, trenbolone, finasteride, flutamide, phthalate esters, selective estrogen receptor modulators and inhibitors of aromatase. Current conclusions are: 1) EDCs appear to induce some LNT effects. 2) NMDRCs are biologically plausible and occur frequently in vitro, but the points of
inflection occur at high concentrations that are not relevant in vivo. 3) NMRDCs appear to be more common a) in short- versus long-term exposures and b) with upstream, mechanistic events vs. downstream phenotypic effects. 4) A few adverse effects of EDCs are non-monotonic, but other effects in these studies displayed monotonic responses at lower dose levels. 5) A number of robust multigenerational studies of estrogens and antiandrogens showed NMDRCs were uncommon at low dose levels. 6) Multigenerational Test guidelines can be enhanced on a case-by-case basis to improve the sensitivity to low dose effects of some EDCs. 7) Additional data needs to be examined from robust, multigenerational studies using a broad range of dosage levels for other toxicity pathways. This abstract does not reflect USEPA policy

Urban-rural status affects associations between domains of environmental quality and adverse birth outcomes

The relationship between environmental conditions and human health varies by environmental domain and urbanicity. To account for multiple ambient environmental conditions, we constructed an Environmental Quality Index (EQI) for health research. We used U.S. county level data representing five environmental domains (air, water, land, built and sociodemographic) and principal components analysis to construct the EQI and domain specific indices for each county (n=3141); counties were categorized by rural-urban continuum codes (RUCC1(most urban) –RUCC4(most rural)) for analyses. Birth outcomes data for one year (2002) from National Center for Health Statistics (n=3,989,704) was associated with categorical (quintiles) EQI domain-specific RUCC-stratified indices. Fixed slope, random intercept multilevel models, adjusted for maternal age, education, marital status, and infant sex, were used to assess associations. Across urban-rural categories, poor air quality (5th quintile(Q) of air domain) was associated with increased preterm birth (PTB= birth at <37 weeks completed gestation) odds (odds ratio (OR) for RUCC1-Q5 = 1.18; 95% confidence intervals (95%CI: 1.11, 1.26)) while exposure to more farmland (5th Q land domain) was associated with lower odds of PTB in all but the most rural RUCC strata (RUCC2-Q5 OR= 0.87; 95% CI: 0.81, 0.93). In all but the most urban strata (RUCC1), exposure to poorer sociodemographic conditions (Q5) was also associated with increased PTB odds (RUCC3-Q5 OR=1.34; 95% CI: 1.25, 1.43). Associations with water and built environment domains were inconsistent across rural-urban status. Similar results were found for very PTB, low birth weight (BW) and very low BW outcomes. While some variability was noted by urban-rural residence, the effect on birth outcomes was generally consistent by domain of environmental quality. The EQI quantifies the environmental burden counties face while the domain specific indices provide policy makers and planners with information regarding primary stressors in the area.
This abstract does not necessarily reflect EPA policy.

Black Holes Have Simple Feeding Habits

At the center of spiral galaxy M81 is a supermassive black hole about 70 million times more massive than our sun.

A study using data from Chandra and ground-based telescopes, combined with detailed theoretical models, shows that the supermassive black hole in M81 feeds just like stellar mass black holes, with masses of only about ten times that of the sun. This discovery supports Einstein’s relativity theory that states black holes of all sizes have similar properties.

Image Credit: X-ray: NASA/CXC/Wisconsin/D.Pooley & CfA/A.Zezas; Optical: NASA/ESA/CfA/A.Zezas; UV: NASA/JPL-Caltech/CfA/J.Huchra et al.; IR: NASA/JPL-Caltech/CfA