httk: R Package for High-Throughput Toxicokinetics

Thousands of chemicals have been profiled by high-throughput screening programs such as ToxCast and Tox21; these chemicals are tested in part because most of them have limited or no data on hazard, exposure, or toxicokinetics. Toxicokinetic models aid in predicting tissue concentrations resulting from chemical exposure, and a "reverse dosimetry" approach can be used to predict exposure doses sufficient to cause tissue concentrations that have been identified as bioactive by high-throughput screening. We have created four toxicokinetic models within the R software package httk. These models are designed to be parameterized using high-throughput in vitro data (plasma protein binding and hepatic clearance), as well as structure-derived physicochemical properties and species-specific physiological data. The package contains tools for Monte Carlo sampling and reverse dosimetry along with functions for the analysis of concentration vs. time simulations. The package can currently use human in vitro data to make predictions for 553 chemicals in humans, rats, mice, dogs, and rabbits, including 94 pharmaceuticals and 415 ToxCast chemicals. For 67 of these chemicals, the package includes rat-specific in vitro data. This package is structured to be augmented with additional chemical data as they become available. Package httk enables the inclusion of toxicokinetics in the statistical analysis of chemicals undergoing high-throughput screening

Challenges in working towards an internal Threshold of Toxicological Concern (iTTC) for use in the safety assessment of cosmetics: Discussions from the Cosmetics Europe iTTC Working Group workshop

The Threshold of Toxicological Concern (TTC) is an important risk assessment tool which establishes acceptable low-level exposure values to be applied to chemicals with limited toxicological data. One of the logical next steps in the continued evolution of TTC is to develop this concept further so that it is representative of internal exposures (TTC based on plasma concentration). An internal TTC (iTTC) would provide threshold values that could be utilized in exposure-based safety assessments. As part of a Cosmetics Europe (CosEu) research program, CosEu has initiated a project that is working towards the development of iTTCs that can be used for the human safety assessment. Knowing that the development of an iTTC is an ambitious and broad-spanning topic, CosEu organized a Working Group comprised a balance of multiple stakeholders (cosmetics and chemical industries, the EPA and JRC and academia) with relevant experience and expertise and workshop to critically evaluate the requirements to establish an iTTC. Outcomes from the workshop included an evaluation on the current state of the science for iTTC, the overall iTTC strategy, selection of chemical databases, capture and curation of chemical information, ADME and repeat dose data, expected challenges, as well as next steps and ongoing work

Granular discharge and clogging for tilted hoppers

We measure the flux of spherical glass beads through a hole as a systematic function of both tilt angle and hole diameter, for two different size beads. The discharge increases with hole diameter in accord with the Beverloo relation for both horizontal and vertical holes, but in the latter case with a larger small-hole cutoff. For large holes the flux decreases linearly in cosine of the tilt angle, vanishing smoothly somewhat below the angle of repose. For small holes it vanishes abruptly at a smaller angle. The conditions for zero flux are discussed in the context of a {\it clogging phase diagram} of flow state vs tilt angle and ratio of hole to grain size

Rectification and Phase Locking for Particles on Two Dimensional Periodic Substrates

We show that a novel rectification phenomena is possible for overdamped particles interacting with a 2D periodic substrate and driven with a longitudinal DC drive and a circular AC drive. As a function of DC amplitude, the longitudinal velocity increases in a series of quantized steps with transverse rectification occuring near these transitions. We present a simple model that captures the quantization and rectification behaviors.Comment: 4 pages, 4 postscript figure

Breaking of general rotational symmetries by multi-dimensional classical ratchets

We demonstrate that a particle driven by a set of spatially uncorrelated, independent colored noise forces in a bounded, multidimensional potential exhibits rotations that are independent of the initial conditions. We calculate the particle currents in terms of the noise statistics and the potential asymmetries by deriving an n-dimensional Fokker-Planck equation in the small correlation time limit. We analyze a variety of flow patterns for various potential structures, generating various combinations of laminar and rotational flows.Comment: Accepted, Physical Review

Superconducting Fluxon Pumps and Lenses

We study stochastic transport of fluxons in superconductors by alternating current (AC) rectification. Our simulated system provides a fluxon pump, "lens", or fluxon "rectifier" because the applied electrical AC is transformed into a net DC motion of fluxons. Thermal fluctuations and the asymmetry of the ratchet channel walls induce this "diode" effect, which can have important applications in devices, like SQUID magnetometers, and for fluxon optics, including convex and concave fluxon lenses. Certain features are unique to this novel two-dimensional (2D) geometric pump, and different from the previously studied 1D ratchets.Comment: Phys. Rev. Lett. 83, in press (1999); 4 pages, 5 .gif figures; figures also available at http://www-personal.engin.umich.edu/~nori/ratche

Hubungan Penggunaan Dan Penanganan Pestisida Pada Petani Bawang Merah Terhadap Residu Pestisida Dalam Tanah Di Lahan Pertanian Desa Wanasari Kecamatan Wanasari Kabupaten Brebes

Excessive use of pesticides causing pollution and environmental damage agriculture. Examination in Brebes on 31 samples of fruits and vegetables, found 22% of samples contain detectable residues of organophosphate and found two soil samples (10%) contained residues organochlorin. The purpose of this study was to determine the relationship of the use and handling of pesticides on their onion farmers against pesticide residues in the soil on agricultural land Wanasari Village, District Wanasari, Brebes. This study is observational method with cross sectional approach. The population in this study were all farmers in the Wanasari conducting spraying. Collecting data using the tool Banu questionnaire and examination of pesticide residues in soil using GC-MS Gas Chromatography - Mass Spectrometry. The results of this study are of 55 69.1 onion farmers use pesticides are not good. The use of pesticides covering 80% is not good in mixing pesticides, 87.3% use a smaller dose, 49.1% use pesticides that are not registered with the Ministry of Agriculture, 87.3% is not good in the way of spraying and 87.3 does well in frequency spraying. Handling pesticides in agricultural land is not good 59.1%, ie 74.5% is not good in handling pesticide containers, 90.9% is not good in storage of pesticides, 89.1% is not good in handling a spill and 87.3% did not either in place to clean pesticide containers. The research result is negative soil samples pesticide residues. The conclusion was that no pesticide residue class organochlorin

Exploring consumer exposure pathways and patterns of use for chemicals in the environment

AbstractHumans are exposed to thousands of chemicals in the workplace, home, and via air, water, food, and soil. A major challenge in estimating chemical exposures is to understand which chemicals are present in these media and microenvironments. Here we describe the Chemical/Product Categories Database (CPCat), a new, publically available (http://actor.epa.gov/cpcat) database of information on chemicals mapped to “use categories” describing the usage or function of the chemical. CPCat was created by combining multiple and diverse sources of data on consumer- and industrial-process based chemical uses from regulatory agencies, manufacturers, and retailers in various countries. The database uses a controlled vocabulary of 833 terms and a novel nomenclature to capture and streamline descriptors of chemical use for 43,596 chemicals from the various sources. Examples of potential applications of CPCat are provided, including identifying chemicals to which children may be exposed and to support prioritization of chemicals for toxicity screening. CPCat is expected to be a valuable resource for regulators, risk assessors, and exposure scientists to identify potential sources of human exposures and exposure pathways, particularly for use in high-throughput chemical exposure assessment