Toxicological evaluation of complex mixtures by pattern recognition: correlating chemical fingerprints to mutagenicity.

We describe the use of pattern recognition and multivariate regression in the assessment of complex mixtures by correlating chemical fingerprints to the mutagenicity of the mixtures. Mixtures were 20 organic extracts of exhaust particles, each containing 102-170 individual compounds such as polycyclic aromatic hydrocarbons (PAHs), nitro-PAHs, oxy-PAHs, and saturated hydrocarbons. Mixtures were characterized by full-scan GC-MS (gas chromatography-mass spectrometry). Data were resolved into peaks and spectra for individual compounds by an automated curve resolution procedure. Resolved chromatograms were integrated, resulting in a predictor matrix that was used as input to a principal component analysis to evaluate similarities between mixtures (i.e., classification). Furthermore, partial least-squares projections to latent structures were used to correlate the GC-MS data to mutagenicity, as measured in the Ames Salmonella assay (i.e., calibration). The best model (high r2 and Q2) identifies the variables that co-vary with the observed mutagenicity. These variables may subsequently be identified in more detail. Furthermore, the regression model can be used to predict mutagenicity from GC-MS chromatograms of other organic extracts. We emphasize that both chemical fingerprints as well as detailed data on composition can be used in pattern recognition

Toxicological evaluation of complex mixtures by pattern recognition: Correlating chemical fingerprints to mutagenicity

We describe the use of pattern recognition and multivariate regression in the assessment of complex mixtures by correlating chemical fingerprints to the mutagenicity of the mixtures. Mixtures were 20 organic extracts of exhaust particles, each containing 102-170 individual compounds such as polycyclic aromatic hydrocarbons (PAHs), nitro-PAHs, oxy-PAHs, and saturated hydrocarbons. Mixtures were characterized by full-scan GC-MS (gas chromatography-mass spectrometry). Data were resolved into peaks and spectra for individual compounds by an automated curve resolution procedure. Resolved chromatograms were integrated, resulting in a predictor matrix that was used as input to a principal component analysis to evaluate similarities between mixtures (i.e., classification). Furthermore, partial least-squares projections to latent structures were used to correlate the GC-MS data to mutagenicity, as measured in the Ames Salmonella assay (i.e., calibration). The best model (high r2 and Q2) identifies the variables that co-vary with the observed mutagenicity. These variables may subsequently be identified in more detail. Furthermore, the regression model can be used to predict mutagenicity from GC-MS chromatograms of other organic extracts. We emphasize that both chemical fingerprints as well as detailed data on composition can be used in pattern recognition.publishedVersio

Relationship between Composition and Toxicity of Motor Vehicle Emission Samples

In this study we investigated the statistical relationship between particle and semivolatile organic chemical constituents in gasoline and diesel vehicle exhaust samples, and toxicity as measured by inflammation and tissue damage in rat lungs and mutagenicity in bacteria. Exhaust samples were collected from “normal” and “high-emitting” gasoline and diesel light-duty vehicles. We employed a combination of principal component analysis (PCA) and partial least-squares regression (PLS; also known as projection to latent structures) to evaluate the relationships between chemical composition of vehicle exhaust and toxicity. The PLS analysis revealed the chemical constituents covarying most strongly with toxicity and produced models predicting the relative toxicity of the samples with good accuracy. The specific nitro-polycyclic aromatic hydrocarbons important for mutagenicity were the same chemicals that have been implicated by decades of bioassay-directed fractionation. These chemicals were not related to lung toxicity, which was associated with organic carbon and select organic compounds that are present in lubricating oil. The results demonstrate the utility of the PCA/PLS approach for evaluating composition–response relationships in complex mixture exposures and also provide a starting point for confirming causality and determining the mechanisms of the lung effects

Computational Visual Stress Level Analysis of Calcareous Algae Exposed to Sedimentation

Osterloff J, Nilssen I, Eide I, de Oliveira Figueiredo MA, de Souza Tâmega FT, Nattkemper TW. Computational Visual Stress Level Analysis of Calcareous Algae Exposed to Sedimentation. PLOS ONE. 2016;11(6): e0157329.This paper presents a machine learning based approach for analyses of photos collected from laboratory experiments conducted to assess the potential impact of water-based drill cuttings on deep-water rhodolith-forming calcareous algae. This pilot study uses imaging technology to quantify and monitor the stress levels of the calcareous algae Mesophyllum engelhartii (Foslie) Adey caused by various degrees of light exposure, flow intensity and amount of sediment. A machine learning based algorithm was applied to assess the temporal variation of the calcareous algae size (∼ mass) and color automatically. Measured size and color were correlated to the photosynthetic efficiency (maximum quantum yield of charge separation in photosystem II, ) and degree of sediment coverage using multivariate regression. The multivariate regression showed correlations between time and calcareous algae sizes, as well as correlations between fluorescence and calcareous algae colors

Automated multivariate analysis of multi-sensor data submitted online: Real-time environmental monitoring.

A pilot study demonstrating real-time environmental monitoring with automated multivariate analysis of multi-sensor data submitted online has been performed at the cabled LoVe Ocean Observatory located at 258 m depth 20 km off the coast of Lofoten-Vesterålen, Norway. The major purpose was efficient monitoring of many variables simultaneously and early detection of changes and time-trends in the overall response pattern before changes were evident in individual variables. The pilot study was performed with 12 sensors from May 16 to August 31, 2015. The sensors provided data for chlorophyll, turbidity, conductivity, temperature (three sensors), salinity (calculated from temperature and conductivity), biomass at three different depth intervals (5-50, 50-120, 120-250 m), and current speed measured in two directions (east and north) using two sensors covering different depths with overlap. A total of 88 variables were monitored, 78 from the two current speed sensors. The time-resolution varied, thus the data had to be aligned to a common time resolution. After alignment, the data were interpreted using principal component analysis (PCA). Initially, a calibration model was established using data from May 16 to July 31. The data on current speed from two sensors were subject to two separate PCA models and the score vectors from these two models were combined with the other 10 variables in a multi-block PCA model. The observations from August were projected on the calibration model consecutively one at a time and the result was visualized in a score plot. Automated PCA of multi-sensor data submitted online is illustrated with an attached time-lapse video covering the relative short time period used in the pilot study. Methods for statistical validation, and warning and alarm limits are described. Redundant sensors enable sensor diagnostics and quality assurance. In a future perspective, the concept may be used in integrated environmental monitoring

Adjustment of Occupational Exposure Limits to Non-Standard Work Schedules

Abstract Non-standard work schedules differ from eight hours per day, five days a week, which is the basis for the occupational exposure limits (OELs). This implies the possibility of increased exposure to agents in the workplace and increased risk of adverse health effects. As a consequence, adjustment factors may be used to provide the same degree of worker protection as the original OELs. There are basically two different approaches for calculating adjustment factors for extended work shifts, either simple linear equations or toxicokinetic models. The toxicokinetic models take into account uptake and elimination of chemical compounds in relation to the daily work period, the number of consecutive working days, and the off-duty periods between tours of duty. For a typical offshore work schedule this implies 12 h per day for 14 consecutive days with off-duty periods of four weeks. Linear models, on the other hand, only take into account either the daily or the weekly exposure which provide different adjustment factors. Furthermore, the linear models do not take into consideration neither work periods exceeding one week nor the off-duty periods. As a consequence, toxicokinetic models are recommended for calculating adjustment factors. In Statoil the requirement has been to use an adjustment factor of 0.6 which is in agreement with the Activities Regulation (§ 36). An adjustment factor of 0.6 is consistent with the worst case adjustment factor obtained from the toxicokinetic model described by Hickey and Reist (1977). The application of the worst case adjustment factor was suggested by Eide (1990) for offshore work schedules and is later referred to as the maximum half-life (MAHL) model. This factor is recommended as an adjustment factor since it will always provide at least the same degree of worker protection as the original OELs, also for most non-standard onshore work schedules. The approach implies that knowledge about the biological half-life of the chemical agents is not required. However, when the biological half-life is known, a more accurate and less conservative adjustment factor can be calculated.</jats:p