Neurotoxicological and thyroid evaluations of rats developmentally exposed to tris(1,3-dichloro-2-propyl)phosphate (TDICPP) and tris(2-chloro-2-ethyl)phosphate(TCEP)

ABSTRACT: Tris(1,3-dichloro-2-propyl)phosphate (TDICPP) and tris(2-chloro-2-ethyl)phosphate (TCEP) are organophosphorous flame retardants with widespread usage and human exposures through food, inhalation, and dust ingestion. They have been detected in human tissues including urine and breast milk. Reports of disrupted neural growth in vitro, abnormal development in larval zebrafish, and altered thyroid hormones in several species have raised concern for neurodevelopmental toxicity. This is especially the case for TDICPP, which is more potent and has more activity in these assays than does TCEP. We evaluated the potential for developmental neurotoxicity of TDICPP and TCEP in a mammalian model. Pregnant Long-Evans rats were administered TDICPP (15, 50, or 150 mg/kg/d) or TCEP (12, 40, 90 mg/kg/d) via oral gavage from gestational day 10 to weaning. Corn oil was the vehicle control in both studies. Body weight and righting reflex development were monitored in all pups. A subset of offspring at culling and weaning, and dams at weaning, were sacrificed for serum and organ collection for measurement of brain, liver, and thyroid weights, serum thyroid levels, and serum and brain acetylcholinesterase activity. Brain weights were also measured in a group of adult TDICPP-treated offspring. One male and one female from each litter were allocated for behavioral testing at several ages: standard locomotor activity (preweaning, postweaning, adults), activity including a lighting change mid-way (postweaning, adults), elevated zero maze (postweaning, adults), functional observational battery (FOB; postweaning, adults), and Morris water maze (place learning, working memory; adults). Neither chemical produced changes in maternal body weight or serum thyroid hormones, but relative liver weight was increased at the high doses of both TDICPP and TCEP. In offspring, there were no effects on viability, litter size, or birth weight. With TDICPP, absolute liver weights were lower at weaning and weight gain was lower in the high-dose offspring until about two months of age. Thyroid hormones and brain weights were not altered, and acetylcholinesterase was not inhibited, by either chemical, TDICPP-treated offspring showed slight differences in floating in the water maze, hindlimb grip strength, and altered activity habituation, whereas TCEP-treated rats showed differences in quadrant time (probe) and middle-zone preference in the water maze. Regarding these few changes, the effects were minimal, mostly not related to dose, and did not appear treatment-related or biologically significant. Overall, these data do not support the potential for thyrotoxicity or developmental neurotoxicity produced by TDICPP or TCEP. 

Locomotor activity and tissue levels following acute administration of lambda- and gamma-cyhalothrin in rats

Pyrethroids produce neurotoxicity that depends, in part, on the chemical structure. Common behavioral effects include locomotor activity changes and specific toxic syndromes (types I and II). In general these neurobehavioral effects correlate well with peak internal dose metrics. Products of cyhalothrin, a type II pyrethroid, include mixtures of isomers (e.g., λ-cyhalothrin) as well as enriched active isomers (e.g., γ-cyhalothrin). We measured acute changes in locomotor activity in adult male rats and directly correlated these changes to peak brain and plasma concentrations of λ- and γ-cyhalothrin using a within-subject design. One-hour locomotor activity studies were conducted 1.5 h after oral gavage dosing, and immediately thereafter plasma and brains were collected for analyzing tissue levels using LC/MS/MS methods. Both isomers produced dose-related decreases in activity counts, and the effective dose range for γ-cyhalothrin was lower than for λ-cyhalothrin. Doses calculated to decrease activity by 50% were 2-fold lower for the γ-isomer (1.29 mg/kg) compared to λ-cyhalothrin (2.65 mg/kg). Salivation, typical of type II pyrethroids, was also observed at lower doses of γ-cyhalothrin. Administered dose correlated well with brain and plasma concentrations, which furthermore showed good correlations with activity changes. Brain and plasma levels were tightly correlated across doses. While γ-cyhalothrin was 2-fold more potent based on administered dose, the differences based on internal concentrations was less, with γ-cyhalothrin being 1.3- to 1.6-fold more potent than λ-cyhalothrin. These potency differences are consistent with the purity of the λ-isomer (approximately 43%) compared to the enriched isomer γ-cyhalothrin (approximately 98%). Thus, administered dose as well as differences in cyhalothrin isomers are a good predictor of behavioral effects.

Assessment of the vitro dermal irritation of cerium silver and titanium nanoparticles in a human skin equivalent model

AbstractDermal exposure to metals may res·ult in irritant contact dermatitis. This study examined the potential of metal nanoparticles to elicit irritant contact dermatitis in a human skin equivalent model (HSEM) derived from epidermal keratinocytes. These cultured cells form a multi-layered,highly differentiated model of human, skin. Several Ag (10-100 nm), Ti02 (22-214 nm) and Ce02 (15-70 nm) nanoparticles were used. The Ag particles were either coated/shelled with silica or capped with citrate or polyvinylpyrrolidone. The Ag nanoparticles were dissolved in water. The Ti02 and Ce02 particles were suspended in cell culture media containing 10% fetal bovine serum. Stock suspensions of these particles were dispersed using a probe sonicator. The particles (1 mg/ml) were applied to the epidermal surface of the HSEM. Three to four wells of HSEM were tested per particle. The positive control was 5% sodium dodecyl sulfate (SDS) and the negative control was either saline or culture media. After 1 h exposure at 37 °C, the HSEM was washed with saline, and then incubated for 42 hat 37 °C, with a change of media at 24 h. Viability of the H~EM was assessed using the MTT assay. A test substance is considered an irritant if the HSEM viability is < 501Yo. The mean viability for the SDS treated HSEM was 7.8%. The viabilities of the nanoparticle treated HSEM were 91% or greater. Under the in vitroconditions used in this study, the Ag, Ti02 and Ce02 nanoparticles examined were not dermal irritants. The formed stratum corneum of the HSEM may limit penetration of metal nanoparticles to induce inflammation and cell death, or their inherent dermal irritancy potential is very low.

Differential Expression of pro-inflammatory and oxidative stress mediators induced by nitrogen dioxide and ozone in primary human bronchial epithelial cells

CONTEXT: N02 and 03 are ubiquitous air toxicants capable of inducing lung damage to the respiratory epithelium. Due to their oxidizing capabilities, these pollutants have been proposed to target specific biological pathways, but few publications have compared the pathways activated.OBJECTIVE: This work will test the premise that N02 and 03 induce toxicity by activating similar cellular pathways.METHODS: Primary human bronchial epithelial cells (HBECs, n = 3 donors) were exposed for 2 h at an air-liquid interface to 3 ppm N02, 0.75 ppm 03, or filtered air and harvested 1 h post­ exposure. To give an overview of pathways that may be influenced by each exposure, gene expression was measured using PCR arrays for toxicity and oxidative stress. Based on the results, genes were selected to quantify whether expression changes were changed in a dose­ and time-response manner using N02 (1, 2, 3, or 5 ppm), 03 (0.25, 0.50, 0.75, or 1.00ppm), orfiltered air and harvesting 0, 1,4 and 24 h post-exposure.RESULTS: Using the arrays, genes related to oxidative stress were highly induced with N02 while expression of pro-inflammatory and vascular function genes was found subsequent to 03. N02 elicited the greatest HMOX1 response, whereas 03 more greatly induced IL-6, IL-8 and PTGS2 expression. Additionally, 03 elicited a greater response 1 h post-exposure and N02 produced a maximal response after 4 h.CONCLUSION: We have demonstrated that these two oxidant gases stimulate differing mechanistic responses in vitro and these responses occur at dissimilar times.

Repeated measures of inflammation, blood pressure, and heart rate variability associated with personal traffic exposures in healthy adults

BACKGROUND: Previous human exposure studies of traffic-related air pollutants have demonstrated adverse health effects in human populations by comparing areas of high and low traffic, but few studies have utilized microenvironmental monitoring of pollutants at multiple traffic locations while looking at a vast array of health endpoints in the same population. We evaluated inflammatory markers, heart rate variablity (HRV), blood pressure,exhaled nitric oxide, and lung function in healthy participants after exposures to varying mixtures of traffic pollutants.METHODS:A repeated-measures, crossover study design was used in which 23 healthy, non­ smoking adults had clinical cardiopulmonary and systemic inflammatory measurements taken prior to, immediately after, and 24 hours after intermittent walking for two hours in the summer months along three diverse roadways having unique emission characteristics. Measurements of PM2.5, PM10, black carbon (BC), elemental carbon (EC), and organic carbon (OC) were collected. Mixed effect models were used to assess changes in health effects associated with these specific pollutant classes.RESULTS: Minimal associations were observed with lung function measurements and the pollutants measured. Small decreases in BP measurements and rMSSD, and increases in IL-1B and the low frequency to high frequency ratio measured in HRV, were observed with increasing concentrations of PM2.5 EC.CONCLUSIONS: Small, acute changes in cardiovascular and inflammation-related effects of microenvironmental exposures to traffic-related air polution were observed in a group of healthy young adults. The associations were most profound with the diesel-source EC.

Drag De-Orbit Device: A New Standard Re-Entry Actuator for CubeSats

Abstract: With the advent of CubeSats, research in Low Earth Orbit (LEO) becomes possible for universities and small research groups. Only a handful of launch sites can be used, due to geographical and political restrictions. As a result, common orbits in LEO are becoming crowded due to the additional launches made possible by low-cost access to space. CubeSat design principles require a maximum of a 25-year orbital lifetime in an effort to reduce the total number of spacecraft in orbit at any time. Ad…

HONDA ( 17V681000 )

Dated: OCT 26, 2017 Honda (American Honda Motor Co.) is recalling certain 2017 Honda CBR1000RR and CBR1000RR SP motorcycles. There may be a gap between the fuel tank cap seal and the fuel filler neck which can allow wat…

JAGUAR ( 17V678000 )

Dated: OCT 26, 2017 Jaguar Land Rover North America, LLC (Jaguar) is recalling certain 2017-2018 Jaguar XF and F-Pace, 2016-2017 Jaguar XJ and 2018 Jaguar XE vehicles. The instrument cluster (IC) may intermittently go b…

LAND ROVER ( 17V679000 )

Dated: OCT 26, 2017 Jaguar Land Rover North America, LLC (Land Rover) is recalling certain 2017 Land Rover Range Rover and Range Rover Sport vehicles. The instrument cluster (IC) may intermittently go blank.

TREMCAR ( 17V680000 )

Dated: OCT 26, 2017 Tremcar is recalling certain 2008-2017 Hutchinson and Tremcar 406 B-train Pups, 2012-2017 Hutchinson and Tremcar 406 2 Axle Semi-Trailers, 2015-2017 Tremcar 406 3 Axle Semi-Trailers, and 2013 Tremcar …

HUTCHINSON ( 17V680000 )

Dated: OCT 26, 2017 Tremcar is recalling certain 2008-2017 Hutchinson and Tremcar 406 B-train Pups, 2012-2017 Hutchinson and Tremcar 406 2 Axle Semi-Trailers, 2015-2017 Tremcar 406 3 Axle Semi-Trailers, and 2013 Tremcar …

FORD ( 17V671000 )

Dated: OCT 24, 2017 Ford Motor Company (Ford) is recalling certain 2017 F-150 vehicles equipped with ten-speed transmissions. The pin that attaches the transmission shift linkage to the transmission may come out, preven…

The 2013 FLEX-US Airborne Campaign at the Parker Tract Loblolly Pine Plantation in North Carolina, USA

Abstract: The first European Space Agency (ESA) and NASA collaboration in an airborne campaign to support ESA’s FLuorescence EXplorer (FLEX) mission was conducted in North Carolina, USA during September-October 2013 (FLEX-US 2013) at the Parker Tract Loblolly Pine (LP) Plantation (Plymouth, NC, USA). This campaign combined two unique airborne instrument packages to obtain simultaneous observations of solar-induced fluorescence (SIF), LiDAR-based canopy structural information, visible through shortwave …

Optimization of Airport Surface Traffic: A Case-Study of Incheon International Airport

Abstract: This study aims to develop a controllers decision support tool for departure and surface management of ICN. Airport surface traffic optimization for Incheon International Airport (ICN) in South Korea was studied based on the operational characteristics of ICN and airspace of Korea. For surface traffic optimization, a multiple runway scheduling problem and a taxi scheduling problem were formulated into two Mixed Integer Linear Programming (MILP) optimization models. The Miles-In-Trail (MIT) se…

Gravity-Assist Trajectories to the Ice Giants: An Automated Method to Catalog Mass- Or Time-Optimal Solutions

Abstract: This work presents an automated method of calculating mass (or time) optimal gravity-assist trajectories without a priori knowledge of the flyby-body combination. Since gravity assists are particularly crucial for reaching the outer Solar System, we use the Ice Giants, Uranus and Neptune, as example destinations for this work. Catalogs are also provided that list the most attractive trajectories found over launch dates ranging from 2024 to 2038. The tool developed to implement this method, ca…

Gravity-Assist Trajectories to the Ice Giants: An Automated Method to Catalog Mass-or Time-Optimal Solutions

Abstract: This work presents an automated method of calculating mass (or time) optimal gravity-assist trajectories without a priori knowledge of the flyby-body combination. Since gravity assists are particularly crucial for reaching the outer Solar System, we use the Ice Giants, Uranus and Neptune, as example destinations for this work. Catalogs are also provided that list the most attractive trajectories found over launch dates ranging from 2024 to 2038. The tool developed to implement this method, ca…

Drag De-Orbit Device: A New Standard Re-Entry Actuator for CubeSats

Abstract: With the advent of CubeSats, research in Low Earth Orbit (LEO) becomes possible for universities and small research groups. Only a handful of launch sites can be used, due to geographical and political restrictions. As a result, common orbits in LEO are becoming crowded due to the additional launches made possible by low-cost access to space. CubeSat design principles require a maximum of a 25-year orbital lifetime in an effort to reduce the total number of spacecraft in orbit at any time. Ad…