Range Of Exposure Durations Research Articles

From vision toward best practices: Evaluating in vitro transcriptomic points of departure for application in risk assessment using a uniform workflow.

The growing number of chemicals in the current consumer and industrial markets presents a major challenge for regulatory programs faced with the need to assess the potential risks they pose to human and ecological health. The increasing demand for hazard and risk assessment of chemicals currently exceeds the capacity to produce the toxicity data necessary for regulatory decision making, and the applied data is commonly generated using traditional approaches with animal models that have limited context in terms of human relevance. This scenario provides the opportunity to implement novel, more efficient strategies for risk assessment purposes. This study aims to increase confidence in the implementation of new approach methods in a risk assessment context by using a parallel analysis to identify data gaps in current experimental designs, reveal the limitations of common approaches deriving transcriptomic points of departure, and demonstrate the strengths in using high-throughput transcriptomics (HTTr) to derive practical endpoints. A uniform workflow was applied across six curated gene expression datasets from concentration-response studies containing 117 diverse chemicals, three cell types, and a range of exposure durations, to determine tPODs based on gene expression profiles. After benchmark concentration modeling, a range of approaches was used to determine consistent and reliable tPODs. High-throughput toxicokinetics were employed to translate in vitro tPODs (µM) to human-relevant administered equivalent doses (AEDs, mg/kg-bw/day). The tPODs from most chemicals had AEDs that were lower (i.e., more conservative) than apical PODs in the US EPA CompTox chemical dashboard, suggesting in vitro tPODs would be protective of potential effects on human health. An assessment of multiple data points for single chemicals revealed that longer exposure duration and varied cell culture systems (e.g., 3D vs. 2D) lead to a decreased tPOD value that indicated increased chemical potency. Seven chemicals were flagged as outliers when comparing the ratio of tPOD to traditional POD, thus indicating they require further assessment to better understand their hazard potential. Our findings build confidence in the use of tPODs but also reveal data gaps that must be addressed prior to their adoption to support risk assessment applications.

Dynamic regulation of gene expression and morphogenesis in the zebrafish embryo test after exposure to all-trans retinoic acid

The zebrafish embryotoxicity test (ZET) is widely used in developmental toxicology. The analysis of gene expression regulation in ZET after chemical exposure provides mechanistic information about the effects of chemicals on morphogenesis in the test. The gene expression response magnitude has been shown to change with exposure duration. The objective of this work is to study the effect of the exposure duration on the magnitude of gene expression changes in the all-trans retinoic acid (ATRA) signaling pathway in the ZET. Retinoic acid regulation is a key driver of morphogenesis and is therefore employed here as an indicator for the regulation of developmental genes. A teratogenic concentration of 7.5 nM of ATRA was given at 3 hrs post fertilization (hpf) for a range of exposure durations until 120 hrs of development. The expression of a selection of genes related to ATRA signaling and downstream developmental genes was determined. The highest magnitudes of gene expression regulation were observed after 2–24 hrs exposure with an optimal response after 4 hrs. Longer exposures showed a decrease in the gene expression response, although continued exposure to 120 hpf caused malformations and lethality. This study shows that assessment of gene expression regulation at early time points after the onset of exposure in the ZET may be optimal for the prediction of developmental toxicity. We believe these results could help optimize sensitivity in future studies with ZET.

Effects of visual span on Chinese reading performance in normal peripheral vision

The current study examined the relationships among temporal processing speed, spatial visual span and Chinese character reading speed in normal central and peripheral vision. Maximum reading speed (MRS) and critical print size (CPS) of 26 native Chinese readers (13 young and 13 older adults) were determined at three visual field locations: central vision, 10° left and 10° below fixation using a rapid serial visual presentation (RSVP) task. Temporal processing speed was measured using trigrams of randomly selected Chinese characters presented at a range of exposure durations, while spatial visual span was measured using trigrams presented at different spatial positions. It was found that shorter temporal processing speed and larger spatial visual span were associated with faster MRS at the central and inferior visual field locations, but not at the left of fixation location. As expected, reading and visual span metrics were better in central vision compared to both peripheral locations. In addition, reading, temporal processing, and spatial visual span metrics were better in the young than older subjects (except for similar temporal processing speed at two peripheral locations). The results for central and inferior presentation locations support the hypothesis that temporal processing speed and spatial visual span were associated with Chinese character reading speed. Surprisingly, no correlation was observed for the 10° left of the fixation location, suggesting that the factors affecting reading speed might differ for inferior and lateral peripheral viewing locations.

Threshold Ocular Exposure to Near Infrared Radiation for Causing Acute Opacification in the Rabbit Lens.

Surveys and epidemiological studies have reported an increased prevalence of cataracts in the glass and steel industries, which are associated with exposure to intense infrared radiation (IR). Indeed, animal studies have demonstrated that IR exposure can produce acute changes in the crystalline lens that are likely to lead to cataract formation. However, little is known about threshold IR exposure for causing acute cataractous changes, which is important in the prevention of IR-induced cataract, especially as a basis for short-term IR exposure limits. Previously, we exposed rabbit eyes to 808 nm wavelength IR at different irradiances for 6 min to determine the threshold irradiance to cause acute lens opacification. Presently, we similarly determined the threshold irradiance for exposure durations of 3 min, 1 min, 30 s, 10 s and 4 s. The threshold irradiance increased steadily with decreasing exposure duration, from 1.1 W cm-2 at 6 min to 4.1 W·cm-2 at 4 s. These threshold values are consistent with ICNIRP exposure limits to avoid IR-induced cataract formation in the tested range of exposure duration, but suggest that it may be necessary to lower the exposure limits for shorter exposure durations.

Modeling the oxidation kinetics of titanium alloys: Review, method and application to Ti-64 and Ti-6242s alloys

The oxidation kinetics of Ti-6Al-4V and Ti-6Al-2Sn-4Zr-2Mo-Si were reviewed in the range 450−650 °C. A method to fit these data was conceived and applied to these alloys, allowing the prediction of mass gain, oxygen diffusion coefficient, embrittlement depth and oxide scale thickness. Prediction diagrams are produced and discussed through the prism of aeronautical applications; discrepancies between modeled and experimental data are discussed. This paper shows that despite Ti-6Al-4V experienced larger mass gains than Ti-6Al-2Sn-4Zr-2Mo-Si, the two alloys have an equivalent behavior in terms of oxygen dissolution and diffusion, over a wide range of exposure durations.

Consequences of winter air exposure on walleye (Sander vitreus) physiology and impairment following a simulated ice-angling event

Length-based harvest restriction is common in fisheries management and can result in a substantial number of fish being released after capture. Science on live release confirms that the practice allows individuals to return to the population and reproduce; however, little is known about how handling practices influence mortality or the sub-lethal physiological alterations in fish that are released during the winter. In this study, walleye (Sander vitreus; Mitchill 1818) were angled through the ice in Lake Nipissing, Ontario to evaluate the contribution of air exposure to the reflex impairment, post-release mortality, and the stress response of fish in the winter. Following 24 h holding, fish were exposed to a simulated angling event and exposed to air or snow across a range of exposure durations. Fish were non-lethally blood sampled and were assessed for reflex impairment and mortality 24 h after capture. No mortalities were recorded during the study and reflex impairment was not linked to exposure type or duration. Blood [lactate] at 1 h post-capture was comparable across treatment groups but was significantly higher than respective baselines. Plasma [cortisol], blood [glucose], and aspartate aminotransferase activities were comparable to baseline levels. Walleye appeared to be resilient to catch-and-release angling in the winter given that no mortalities occurred and fish suffered minimal reflex impairment and physiological disturbance following capture. Findings from this study suggest that mandatory catch-and-release regulations for sub-adult walleye are a useful tool for the management of winter walleye ice fisheries.

The magical number one-on-square-root-two: The double-target detection deficit in brief visual displays.

How limited representational capacity is divided when multiple items need to be processed simultaneously is a fundamental question in cognitive psychology. The double-target deficit is the finding that, when monitoring multiple locations or information streams for targets, identification of 2 simultaneous targets is substantially worse than is predicted from the cost of divided attention alone. This finding suggests that targets and nontargets are treated differently by the cognitive system. We investigated the double-target deficit in 4 different visual decision tasks using noisy, backwardly masked targets presented for a range of exposure durations to test the theory that the deficit reflects a capacity limitation of visual short-term memory (VSTM). We quantified the deficit using a sample-size model of VSTM and 2 different models of the decision process: a signal detection MAX model and an optimum likelihood ratio model. We found a double-target deficit in all 4 tasks which increased in magnitude for briefer displays, consistent with the capacity limits of VSTM. We explained the exposure dependency using a competitive interaction model in which nontargets compete for access to VSTM at a slower rate than targets. Our findings support 2-stage models of visual processing in which the most target-like stimuli gain priority access into VSTM before the decision process begins. (PsycINFO Database Record

Developmental bisphenol A exposure impairs sperm function and reproduction in zebrafish

The developmental and reproductive toxicity of bisphenol A (BPA) has been demonstrated in a variety of model systems. Zebrafish (Danio rerio) were waterborne-exposed to BPA during three different developmental stages: embryonic period:6 h post fertilization (hpf) to 5 months post fertilization (mpf); larval period: 6 days post fertilization (dpf) to 5 mpf; and sexually mature period: 3 mpf to 5 mpf. Evaluations included F0 adult growth, reproduction parameters, and F1 offspring development. BPA exposure did not affect zebrafish growth in any of exposure groups. Testis weight was decreased only following the 6 hpf to 5 mpf 0.001 μM BPA exposure. The lowest effect level indicated by a reduction in sperm volume, density, motility, and velocity across a range of exposure durations was 0.001 μM, with all but sperm density significant for the longest exposure duration, which was also the only significant endpoint for the lowest exposure concentration in the 3–5 mpf exposure group. Nonmonotonic concentration-response curves were noted for all F0 reproductive endpoints for at least one of the two longest exposure durations. For the F1 offspring of fish exposed from 6 hpf to 5 mpf, malformations and mortality were increased following 0.001 μM BPA exposure, while egg production and fertilization were reduced in higher concentration treatment groups. Overall, BPA exposure during three different developmental periods impaired zebrafish reproductive development, with most significance changes found in the lowest concentration treatment groups. Genetic impacts on gamete development may underlie the secondary effects of reduced fertilization rate, embryonic mortality, and malformations.

Moderate prenatal alcohol exposure and quantification of social behavior in adult rats.

Alterations in social behavior are among the major negative consequences observed in children with Fetal Alcohol Spectrum Disorders (FASDs). Several independent laboratories have demonstrated robust alterations in the social behavior of rodents exposed to alcohol during brain development across a wide range of exposure durations, timing, doses, and ages at the time of behavioral quantification. Prior work from this laboratory has identified reliable alterations in specific forms of social interaction following moderate prenatal alcohol exposure (PAE) in the rat that persist well into adulthood, including increased wrestling and decreased investigation. These behavioral alterations have been useful in identifying neural circuits altered by moderate PAE(1), and may hold importance for progressing toward a more complete understanding of the neural bases of PAE-related alterations in social behavior. This paper describes procedures for performing moderate PAE in which rat dams voluntarily consume ethanol or saccharin (control) throughout gestation, and measurement of social behaviors in adult offspring.

Porcine skin damage thresholds for 0.6 to 9.5 cm beam diameters from 1070-nm continuous-wave infrared laser radiation

There is an increasing use of high-power fiber lasers in manufacturing and telecommunications industries operating in the infrared spectrum between 1000 and 2000 nm, which are advertised to provide as much as 10 kW continuous output power at 1070 nm. Safety standards have traditionally been based on experimental and modeling investigations with scant data available for these wavelengths. A series of studies using 1070-nm infrared lasers to determine the minimum visible lesion damage thresholds in skin using the Yucatan miniature pig (Sus scrofa domestica) for a range of beam diameters (0.6, 1.1, 1.9, 2.4, 4.7, and 9.5 cm) and a range of exposure durations (10 ms to 10 s) is presented. Experimental peak temperatures associated with each damage threshold were measured using thermal imaging. Peak temperatures at damage threshold for the 10-s exposures were ∼10°C lower than those at shorter exposures. The lowest and highest experimental minimum visible lesion damage thresholds were found to have peak radiant exposures of 19 and 432 J/cm2 for the beam diameter-exposure duration pairs of 2.4 cm, 25 ms and 0.6 cm, 10 s, respectively. Thresholds for beam diameters >2.5 cm had a weak to no effect on threshold radiant exposure levels for exposure times ≤0.25 s, but may have a larger effect on thresholds for exposures ≥10 s.

Effects of stimulus duration and inter-letter spacing on letter-in-string identification

Effects of stimulus duration and inter-letter spacing were studied in a letter-in-string identification paradigm. Participants were shown strings of 5 random consonants (e.g., PGKDM) centered on fixation and were asked to identify the letter that had appeared at a post-cued location. Stimulus duration was manipulated in Experiment 1 (13ms–91ms), and inter-letter spacing manipulated in Experiment 2 (for a fixed stimulus duration of 26ms). We contrasted performance to outer-letters (positions 1 and 5) with non-central inner letters (positions 2 and 4), the first-letter (position 1) with the final letter (position 5), and the central-letter (position 3) with the other inner letters (positions 2 and 4). The outer-letter advantage and the first-letter advantage were present throughout the entire range of exposure durations, whereas the central-letter advantage increased with longer exposures. On the other hand, increased spacing reduced both the outer-letter advantage and the first-letter advantage, whereas it led to a greater central-letter advantage. Changes in acuity and crowding as a function of stimulus exposure and inter-letter spacing, can account for this pattern of results.

REVIEW OF THRESHOLDS AND RECOMMENDATIONS FOR REVISED EXPOSURE LIMITS FOR LASER AND OPTICAL RADIATION FOR THERMALLY INDUCED RETINAL INJURY

Exposure limits (ELs) for laser and optical broadband radiation that are derived to protect the retina from adverse thermally-induced effects vary as a function of wavelength, exposure duration, and retinal irradiance diameter (spot size) expressed as the angular subtense α. A review of ex vivo injury threshold data shows that, in the ns regime, the microcavitation-induced damage mechanism results in retinal injury thresholds below thermal denaturation-induced thresholds. This appears to be the reason that the injury thresholds for retinal spot sizes of about 80 μm (α = 6 mrad) and pulse durations of about 5 ns in the green wavelength range are very close to current ELs, calling for a reduction of the EL in the ns regime. The ELs, expressed in terms of retinal radiant exposure or radiance dose, currently exhibit a 1/α dependence up to a retinal spot size of 100 mrad, referred to as αmax. For α ≥ αmax, the EL is a constant retinal radiant exposure (no α dependence) for any given exposure duration. Recent ex vivo, computer model, and non-human primate in vivo threshold data provide a more complete assessment of the retinal irradiance diameter dependence for a wide range of exposure durations. The transition of the 1/α dependence to a constant retinal radiant exposure (or constant radiance dose) is not a constant αmax but varies as a function of the exposure duration. The value of αmax of 100 mrad reflects the spot size dependence of the injury thresholds only for longer duration exposures. The injury threshold data suggest that αmax could increase as a function of the exposure duration, starting in the range of 5 mrad in the μs regime, which would increase the EL for pulsed exposure and extended sources by up to a factor of 20, while still assuring an appropriate reduction factor between the injury threshold and the exposure limit.

Effects of near‐infrared laser exposure in a cellular model of wound healing

Clinical studies have demonstrated beneficial outcomes for low-level laser therapy (LLLT) using near-infrared (NIR) wavelengths. It has been hypothesized that the benefits of NIR LLLT are due in part to the thermal effects of NIR exposure. However, it is not clear whether photochemical interactions between NIR light and superficial tissues contribute to beneficial outcomes. To investigate the photochemical effects of NIR exposure, the efficacy of 980 nm NIR LLLT on human fibroblast growth rates is investigated using an in vitro model of wound healing. A small pipette is used to induce a wound in fibroblast cell cultures, which are imaged at specific time intervals over 48 h and exposed to a range of laser doses (1.5-66 J/cm(2)) selected to encompass the range of doses used during other in vivo and in vitro studies. For each image acquired, wound sizes were quantified using a novel application of existing image processing algorithms. Cell growth rates were compared across different laser exposure intensities with the same exposure duration, and across different laser exposure durations with the same exposure intensity. Exposure to low- and medium-intensity laser light accelerates cell growth, whereas high-intensity light negated the beneficial effects of laser exposure. Cell growth was accelerated over a wide range of exposure durations using medium-intensity laser light, with no significant inhibition of cell growth at the longest exposure durations used in this study. Low-level exposure to 980 nm laser light can accelerate wound healing in vitro without measurable temperature increases. However, these results also demonstrate the need for appropriate supervision of laser therapy sessions to prevent overexposure to NIR laser light that may inhibit cell growth rates observed in response to lower intensity laser exposure.

The role of reentrant processes in feature binding: Evidence from neuropsychology and TMS on late onset illusory conjunctions

We report data on illusory conjunctions (ICs) in a colour/letter identification task from a patient with simultanagnosia following bilateral parietal lesions and from a study using transcranial magnetic stimulation (TMS) with normal participants. We show that, even though target conjunctions were reported well above chance across a range of exposure durations, ICs were only generated at longer display exposures while feature errors decreased across time. With normal participants we found that TMS to the right posterior parietal cortex but not to occipital cortex increased the number of ICs. Moreover, ICs tended to occur after delayed stimulation, with the critical time window for stimulation being later for ICs than for feature errors. The data provide support for the critical role of posterior parietal cortex in a late process of feature binding.

Clostridium difficile in the Intensive Care Unit: Epidemiology, Costs, and Colonization Pressure

To evaluate the epidemiology, outcomes, and importance of Clostridium difficile colonization pressure (CCP) as a risk factor for C. difficile-associated disease (CDAD) acquisition in intensive care unit (ICU) patients. Secondary analysis of data from a 30-month retrospective cohort study. A 19-bed medical ICU in a midwestern tertiary care referral center. Consecutive sample of adult patients with a length of stay of 24 hours or more between July 1, 1997, and December 31, 1999. Seventy-six (4%) of 1,872 patients were identified with CDAD; 40 (53%) acquired CDAD in the ICU, for an incidence of 3.2 cases per 1,000 patient-days. Antimicrobial therapy, enteral feeding, mechanical ventilation, vancomycin-resistant enterococci (VRE) colonization or infection, and CCP (5.5 vs 2.0 CDAD case-days of exposure for patients with acquired CDAD vs no CDAD; P=.001) were associated with CDAD acquisition in the univariate analysis. Only VRE colonization or infection (45% of patients with acquired CDAD vs 16% of patients without CDAD; adjusted odds ratio, 2.76 [95% confidence interval, 1.36-5.59]) and a CCP of more than 30 case-days of exposure (20% with acquired CDAD vs 2% with no CDAD; adjusted odds ratio, 3.77 [95% confidence interval, 1.14-12.49]) remained statistically significant in the multivariable analysis. Lengths of stay (6.1 vs 3.0 days; P<.001 by univariate analysis) and ICU costs ($11,353 vs $6,028; P<.001 by univariate analysis) were higher for patients with any CDAD than for patients with no CDAD. In this nonoutbreak setting, the CCP was an independent risk factor for acquisition of CDAD in the ICU at the upper range of exposure duration. Having CDAD in the ICU was a marker of excess healthcare use.

Statistical estimation of resin composite polymerization sufficiency using microhardness

With respect to determining sub-surface resin polymerization sufficiency, this study compared a traditional method of applying linear regression to bottom- to top-surface Knoop hardness ratios to an alternative method based on nonlinear regression. Inverse linear regression on ratios was used to estimate the exposure duration required for 80% bottom-surface hardness with respect to the top, in six light-by-material groups. Alternatively, a one-phase, two-parameter, exponential association of the form Y= Y max(1−e − kt ) (where Y max is maximum hardness, k is a rate constant, and t is exposure duration), was used to model hardness. Inverse nonlinear regression estimated, for each condition, the exposure duration required for the bottom surface to achieve 80% of corresponding condition (light and material) top-surface Y max. Mathematically, analysis of ratios was demonstrated to yield potentially less precise and biased estimates. Nonlinear regression yielded better statistical fit and provided easily accessible tests for differences in k across light-system groups. Another recently proposed nonlinear model for polymerization, Y= Y max kt n /(1+ kt n ), was also considered. While this new model has substantially greater phenomenological and mechanistic justification, we found that the model-fitting process was more sensitive to initial parameter values and sometimes yielded untenable results when applied to our data. However, we believe that these problems would not occur if sample points are well distributed across a wide range of exposure durations, and that the model, Y= Y max kt n /(1+ kt n ), should be considered for such data sets.

Reevaluation of Polychlorinated Biphenyl Concentrations in Milk and Body Fat of Lactating Cows

Polychlorinated biphenyls occur as mixtures of congeners, each of which may be absorbed, excreted, or metabolized differently. Quantification of polychlorinated biphenyls by packed-column GLC has been difficult. Many quantification techniques, generally based on quantification of a selected group of the congeners present, have been used by researchers. Results of these studies have not provided a consistent basis to determine the relationship between the amounts of polychlorinated biphenyls consumed and residual polychlorinated biphenyls in milk and animal tissues. In the present study, we hypothesized that if a standardized quantification procedure was applied, consistent dose:residue predictions could be made. Weighted percentage of each peak in the polychlorinated biphenyl mixture procedures was used as a standard method to quantify polychlorinated biphenyls in milk fat from published and unpublished studies where lactating cows were fed between 3.5 and 1000 mg/d (Aroclor 1254) for ⩾15 d. When steady state occurred by 60 d of dosing, the relationship between concentration in milk fat (μg/g) and daily dose as mg and as mgkg BW were described by the equations: [polychlorinated biphenyls, μg/g]milk fat = .28(daily dose, mg).82, and [polychlorinated biphenyls, μg/g]milk fat = 50.2(daily dose, mg BW).81 Similar equations described the relationships between daily dose and concentrations in adipose tissue and blood plasma. Concentrations of polychlorinated biphenyls residues in milk fat of 79 animals that were dosed with known quantities of polychlorinated biphenyls for 15 to 107 d confirmed that the equations could be valuable in predicting exposure over a wide range of exposure durations and concentrations.

Threshold dosages for damage to mammalian liver by high intensity focused ultrasound

The threshold dosages for high-intensity focal lesion production were determined at 3 MHz in the cat liver for exposure durations covering the range 0.003-35 s. The liver threshold was found to parallel that for the brain over the range of exposure durations 0.1 to 10 s, but to be more than twice the intensity level, approximately following the relation IT(0.5)=460 W-cm(2)/s(2), where I is the peak intensity and T is the exposure duration. At shorter exposure durations the threshold curve deviates from this relation, probably due to a change to a transient cavitation mechanism of damage.

Different encoding mechanisms for phase and contrast

Phase sensitivity was assessed over a large range of exposure durations by means of a 2AFC staircase procedure where the observer had to detect the relative position of sinusoidal gratings relative to a superimposed thin, dark line. Phase discrimination thresholds decreased as a function of exposure duration although the contrast of the stimuli was weighted for equal detectability at all durations. Phase sensitivity improved markedly with contrast, as opposed to the degradation with contrast seen in contrast discrimination paradigms. The contrast and time functions of phase sensitivity both support the hypothesis that phase is processed separately from contrast by a pathway with different temporal and contrast characteristics. We propose a model where phase sensitivity depends on a luminance subtraction process with a time constant of about 130 msec.

Acute motor and lethal effects of inhaled toluene, 1,1,1-trichloroethane, halothane, and ethanol in mice: Effects of exposure duration

Some acute effects of inhalation exposure to toluene, 1,1,1-trichloroethane (1,1,1-TCE), halothane, and ethanol were examined in mice. Lethality and performance on an inverted screen test of motor performance were measured following 10-, 30-, and 60-min exposures. Concentration-dependent effects were obtained on both measures for all solvents except that lethal concentrations of ethanol could not be produced under these exposure conditions. Lethality increased with longer exposures for toluene, 1,1,1-TCE, and halothane. Sensitivity to the motor effects of 1,1,1-TCE, halothane, and ethanol increased when exposure duration was increased from 10 to 30 min, with no further change with 60-min exposures. In contrast, behavioral sensitivity to toluence increased over the entire range of exposure durations. The relative lipid solubilities of the solvents correlate with potency for behavioral activity but not as well with potency for lethality. The ratio of potency for motor and lethal effects depended on the chemical studied and in some cases exposure duration. These results demonstrate that both concentration and exposure duration determine the effects of inhaled compounds, but a simple linear relationship does not exist and it depends upon the effect measured.