Correlation of tissue concentrations of the pyrethroid bifenthrin with neurotoxicity in the rat

The potential for human exposure to pyrethroid pesticides has prompted pharmacodynamic and pharmacokinetic research to better characterize risk. This work tested the hypothesis that blood and brain concentrations of the pyrethroid bifenthrin are predictive of neurotoxic effects. Adult male Long Evans rats received a single oral dose of bifenthrin dissolved in corn oil. Using figure-eight mazes, motor activity was measured for 1h at 4- and 7-h following exposure to bifenthrin (0-16mg/kg or 0-9mg/kg, respectively; n=4-8/group). Whole blood and brains were collected immediately following motor activity assays. Bifenthrin concentrations in blood and brain were quantified using HPLC/MS/MS. Bifenthrin exposure decreased motor activity from 20% to 70% in a dose-dependent manner at both time points. The relationship between motor activity data and administered dose, and blood and brain bifenthrin concentrations were described using a sigmoidal E max model. The relationships between motor activity and administered dose or blood concentrations were different between the 4- and 7-h time points. The relationship between motor activity and brain concentration was not significantly different between the two time points. These data suggest that momentary brain concentration of bifenthrin may be a more precise dose metric for predicting behavioral effects because the relationship between brain concentration and locomotor activity is independent of the time of exposure.Fil: Scollon, Edward J.. National Health And Environmental Effects Research Laboratory; Estados UnidosFil: Starr, James M.. United States Environmental Protection Agency; Estados UnidosFil: Crofton, Kevin M.. National Health And Environmental Effects Research Laboratory; Estados UnidosFil: Wolansky, Marcelo Javier. National Research Council; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: DeVito, Michael J.. National Health And Environmental Effects Research Laboratory; Estados UnidosFil: Hughes, Michael F.. National Health And Environmental Effects Research Laboratory; Estados Unido

Using High Resolution LiDAR Data and a Flux Footprint Parameterization to Scale Evapotranspiration Estimates to Lower Pixel Resolutions

Over the last several decades the hydrologically sensitive Boreal Plains ecoregion of Western Canada has experienced significant warming and drying. To better predict implications of land cover changes on evapotranspiration (ET) and future water resources in this region, high resolution light detection and ranging and energy balance data are used here to spatially parameterize the Penman-Monteith ET model. Within a 5 km × 5 km area of peatland ecosystems, riparian boundaries, and upland mixedwood forests, the influence of land cover heterogeneity on the accuracy of modeled ET is examined at pixel sizes of 1, 10, 25, 250, 500, and 1,000 m, representing resolutions common to popular satellite products (SPOT, Landsat, and MODIS). Modeled ET was compared with tower-based eddy covariance measurements using a weighted flux footprint model. Errors range from 10% to 36% of measured fluxes and results indicate that sensors with small pixel sizes (1 m) offer significantly better accuracy in large heterogeneous flux footprints, while a wider range of pixel sizes (500 m) pixel sizes offered significantly less accuracy, although changes in pixel size within this range offered comparable results

Short-term Exposure to Triclosan Decreases Thyroxine In Vivo via Upregulation of Hepatic Catabolism in Young Long-Evans Rats

Triclosan (5-chloro-2-(2,4-dichlorophenoxy)-phenol) is a chlorinated phenolic antibacterial compound found in consumer products. In vitro human pregnane X receptor activation, hepatic phase I enzyme induction, and decreased in vivo total thyroxine (T4) suggest adverse effects on thyroid hormone homeostasis. Current research tested the hypothesis that triclosan decreases circulating T4 via upregulation of hepatic catabolism and transport. Weanling female Long-Evans rats received triclosan (0–1000 mg/kg/day) by gavage for 4 days. Whole blood and liver were collected 24 h later. Total serum T4, triiodothyronine (T3), and thyroid-stimulating hormone (TSH) were measured by radioimmunoassay. Hepatic microsomal assays measured ethoxyresorufin-O-deethylase, pentoxyresorufin-O-deethylase (PROD), and uridine diphosphate glucuronyltransferase enzyme activities. The messenger RNA (mRNA) expression of cytochrome P450s 1a1, 2b1/2, and 3a1/23; UGTs 1a1, 1a6, and 2b5; sulfotransferases 1c1 and 1b1; and hepatic transporters Oatp1a1, Oatp1a4, Mrp2, and Mdr1b was measured by quantitative reverse transcriptase PCR. Total T4 decreased dose responsively, down to 43% of control at 1000 mg/kg/day. Total T3 was decreased to 89 and 75% of control at 300 and 1000 mg/kg/day. TSH did not change. Triclosan dose dependently increased PROD activity up to 900% of control at 1000 mg/kg/day. T4 glucuronidation increased nearly twofold at 1000 mg/kg/day. Cyp2b1/2 and Cyp3a1/23 mRNA expression levels were induced twofold and fourfold at 300 mg/kg/day. Ugt1a1 and Sult1c1 mRNA expression levels increased 2.2-fold and 2.6-fold at 300 mg/kg/day. Transporter mRNA expression levels were unchanged. These data denote important key events in the mode of action for triclosan-induced hypothyroxinemia in rats and suggest that this effect may be partially due to upregulation of hepatic catabolism but not due to mRNA expression changes in the tested hepatic transporters

Thyroid-Hormone–Disrupting Chemicals: Evidence for Dose-Dependent Additivity or Synergism

Endocrine disruption from environmental contaminants has been linked to a broad spectrum of adverse outcomes. One concern about endocrine-disrupting xenobiotics is the potential for additive or synergistic (i.e., greater-than-additive) effects of mixtures. A short-term dosing model to examine the effects of environmental mixtures on thyroid homeostasis has been developed. Prototypic thyroid-disrupting chemicals (TDCs) such as dioxins, polychlorinated biphenyls (PCBs), and poly-brominated diphenyl ethers have been shown to alter thyroid hormone homeostasis in this model primarily by up-regulating hepatic catabolism of thyroid hormones via at least two mechanisms. Our present effort tested the hypothesis that a mixture of TDCs will affect serum total thyroxine (T(4)) concentrations in a dose-additive manner. Young female Long-Evans rats were dosed via gavage with 18 different polyyhalogenated aromatic hydrocarbons [2 dioxins, 4 dibenzofurans, and 12 PCBs, including dioxin-like and non-dioxin-like PCBs] for 4 consecutive days. Serum total T(4) was measured via radioimmunoassay in samples collected 24 hr after the last dose. Extensive dose–response functions (based on seven to nine doses per chemical) were determined for individual chemicals. A mixture was custom synthesized with the ratio of chemicals based on environmental concentrations. Serial dilutions of this mixture ranged from approximately background levels to 100-fold greater than background human daily intakes. Six serial dilutions of the mixture were tested in the same 4-day assay. Doses of individual chemicals that were associated with a 30% TH decrease from control (ED(30)), as well as predicted mixture outcomes were calculated using a flexible single-chemical-required method applicable to chemicals with differing dose thresholds and maximum-effect asymptotes. The single-chemical data were modeled without and with the mixture data to determine, respectively, the expected mixture response (the additivity model) and the experimentally observed mixture response (the empirical model). A likelihood-ratio test revealed statistically significant departure from dose additivity. There was no deviation from additivity at the lowest doses of the mixture, but there was a greater-than-additive effect at the three highest mixtures doses. At high doses the additivity model underpredicted the empirical effects by 2- to 3-fold. These are the first results to suggest dose-dependent additivity and synergism in TDCs that may act via different mechanisms in a complex mixture. The results imply that cumulative risk approaches be considered when assessing the risk of exposure to chemical mixtures that contain TDCs

Severe wildfire exposes remnant peat carbon stocks to increased post-fire drying

Abstract The potential of high severity wildfires to increase global terrestrial carbon emissions and exacerbate future climatic warming is of international concern. Nowhere is this more prevalent than within high latitude regions where peatlands have, over millennia, accumulated legacy carbon stocks comparable to all human CO2 emissions since the beginning of the industrial revolution. Drying increases rates of peat decomposition and associated atmospheric and aquatic carbon emissions. The degree to which severe wildfires enhance drying under future climates and induce instability in peatland ecological communities and carbon stocks is unknown. Here we show that high burn severities increased post-fire evapotranspiration by 410% within a feather moss peatland by burning through the protective capping layer that restricts evaporative drying in response to low severity burns. High burn severities projected under future climates will therefore leave peatlands that dominate dry sub-humid regions across the boreal, on the edge of their climatic envelopes, more vulnerable to intense post-fire drying, inducing high rates of carbon loss to the atmosphere that amplify the direct combustion emissions

Developmental triclosan exposure decreases maternal, fetal, and early neonatal thyroxine: A dynamic and kinetic evaluation of a putative mode-of-action

This work tests the mode-of-action (MOA) hypothesis that maternal and developmental triclosan (TCS) exposure decreases circulating thyroxine (T4) concentrations via up-regulation of hepatic catabolism and elimination of T4. Time-pregnant Long-Evans rats received TCS po (0–300 mg/kg/day) from gestational day (GD) 6 through postnatal day (PND) 21. Serum and liver were collected from dams (GD20, PND22) and offspring (GD20, PND4, PND14, PND21). Serum T4, triiodothyronine (T3), and thyroid stimulating hormone (TSH) concentrations were measured by radioimmunoassay. Ethoxy-O-deethylase (EROD), pentoxyresorufin-O-depentylase (PROD) and uridine diphosphate glucuronyltransferase (UGT) enzyme activities were measured in liver microsomes. Custom Taqman® qPCR arrays were employed to measure hepatic mRNA expression of select cytochrome P450s, UGTs, sulfotransferases, transporters, and thyroid-hormone responsive genes. TCS was quantified by LC/MS/MS in serum and liver. Serum T4 decreased approximately 30% in GD20 dams and fetuses, PND4 pups and PND22 dams (300 mg/kg/day). Hepatic PROD activity increased 2- to 3-fold in PND4 pups and PND22 dams, and UGT activity was 1.5-fold higher in PND22 dams only (300 mg/kg/day). Minor up-regulation of Cyp2b and Cyp3a expression in dams was consistent with hypothesized activation of the constitutive androstane and/or pregnane X receptor. T4 reductions of 30% for dams and GD20 and PND4 offspring with concomitant increases in PROD (PND4 neonates and PND22 dams) and UGT activity (PND22 dams) suggest that up-regulated hepatic catabolism may contribute to TCS–induced hypothyroxinemia during development. Serum and liver TCS concentrations demonstrated greater fetal than postnatal internal exposure, consistent with the lack of T4 changes in PND14 and PND21 offspring. These data support the MOA hypothesis that TCS exposure leads to hypothyroxinemia via increased hepatic catabolism; however, the minor effects on thyroid hormone metabolism may reflect the low efficacy of TCS as thyroid hormone disruptor or highlight the possibility that other MOAs may also contribute to the observed maternal and early neonatal hypothyroxinemia