Hormesis and plant biology

A database has been developed that demonstrates experimental evidence of hormesis. It includes information from a broad range of biological models, including plants, and information on study design, dose-response features, and physical/chemical properties of the agents. An assessment of plant hormetic dose responses is presented based on greater than 3000 plant endpoints. Plant hormetic dose responses were observed for numerous endpoints including disease incidence, reproductive indices, mutagenic endpoints, various metabolic parameters, developmental processes, and a range of growth indicators. Quantitative features of these dose responses typically display a maximum stimulatory response less than two-fold greater than controls and a width of the stimulatory response usually less than 10-fold in dose range. The database establishes that hormetic dose responses commonly occur in plants, are broadly generalizable, and have quantitative features similar to hormetic dose responses found for animals.     

Hormesis: considerations and implications for human health risk assessment

The concept of hormesis as a phenomenon is presented, in the context of its evolving definitions. Predominant types of hormetic effect and potential examples thereof are discussed, focusing on chemicals. The potential for hormesis to affect regulatory approaches and several basic processes used in formulating risk assessment parameters, such as study design, interpretation of dose-response information, and extrapolation of toxicity values, is examined. The potential ramifications for human health risk assessment and risk management are discussed.     

Novel approach to predicting hormetic effects of antibiotic mixtures on Vibrio fischeri

The determination of the hormetic effects of a mixture is quite difficult because of the moderate simulation and the complexity of measurement in low doses. In the present study, two typical models for mixture toxicity prediction, concentration additive (CA) and independent action (IA), were used to predict the hormetic effects of mixtures. The predictive power of those models was validated by the hormetic effects (24-h exposure) of antibiotic’s binary mixtures to Vibrio fischeri. The results showed that CA and IA were unable to predict the hormetic dose-response of mixture, especially those of the interactive mixtures. As an alternative, a novel model, which was named as “six-point” and developed based on the quantitative features in the determined dose-response curve and on the Quantitative Structure Activity Relationships (QSARs) approach, was proposed for predicting the hormetic effects of mixtures in low dose. The results indicated that the “six-point” model can accurately predict the mixture hormetic effects in low dose, not only for non-interactive mixtures but also for interactive mixtures. Therefore, the “six-point” model is a powerful tool to predict the mixture hormetic effects at low dose, and may offer an important approach in the environment risk assessment of mixtures.     

The hormetic effect of cadmium on the activity of antioxidant enzymes in the earthworm Eisenia fetida

The hormetic dose–response relationships induced by environmental toxic agents are often characterized by low-dose stimulation and high-dose inhibition. Confirmation of the general phenomenon of hormesis may have significant implications for ecological risk assessment, although the mechanisms that underlie hormesis remain an enigma. In this study, a model-based approach for describing a dose–response relationship incorporating the hormetic effect was applied to the detection and estimation of the hormetic effect of cadmium (Cd) on the activity of antioxidant enzymes in the earthworm Eisenia fetida. The results showed that Cd at low concentrations induced an increase in the activity of catalase and superoxide dismutase (SOD), but high concentrations inhibited the enzymes, and this was reflected in an inverted U-shaped curve. The maximum hormetic magnitude of SOD activity was higher than that of catalase. The presence of hormesis induced by cadmium in the earthworm may be related to activation of adaptive pathways.     

Potential Impact on Standards for Toxic Air Contaminants

Since the Bhopal incident, the public has placed pressure on regulatory agencies to set community exposure limits for the dozens of chemicals that may be released by manufacturing facilities. More or less objective limits can be established for the vast majority of these chemicals through the use of risk assessment. However, each step of the risk assessment process (i.e., hazard identification, dose-response assessment, exposure assessment, and risk characterization) contains a number of pitfalls that scientists need to avoid to ensure that valid limits are established. For example, in the hazard identification step there has been little discrimination among animal carcinogens with respect to mechanism of action or the epidemiology experience. In the dose-response portion, rarely is the range of “plausible” estimated risks presented. Physiologically based pharmacokinetic (PB-PK) models should be used to understand the difference between the tissue doses and the administered dose, as well as the difference in target tissue concentrations of the toxicant between rodents and humans. Biologically-based models like the Moolgavkar-Knudson-Venzon (MKV) should be developed and used, when appropriate. The exposure assessment step can be significantly improved by using more sensitive and specific sampling and analytical methods, more accurate exposure parameters, and computer models that can account for complex environmental factors. Whenever possible, model predictions of exposure and uptake should be validated by biological monitoring of exposed persons (urine, blood, adipose) or by field measurements of plants, soil, fish, air, or water. In each portion of an assessment, the weight of evidence approach should be used to identify the most defensible value. In the risk characterization, the best estimate of the potential risk as well as the highest plausible risk should be presented. Future assessments would be much improved if quantitative uncertainty analyses were conducted. Procedures are currently available for making future assessments. By correcting some of these shortcomings in how health risk assessments have been conducted, scientists and risk managers should be better able to identify scientifically appropriate ambient air standards and emission limits.     

The current practice of health risk assessment: potential impact on standards for toxic air contaminants

Since the Bhopal incident, the public has placed pressure on regulatory agencies to set community exposure limits for the dozens of chemicals that may be released by manufacturing facilities. More or less objective limits can be established for the vast majority of these chemicals through the use of risk assessment. However, each step of the risk assessment process (i.e., hazard identification, dose-response assessment, exposure assessment, and risk characterization) contains a number of pitfalls that scientists need to avoid to ensure that valid limits are established. For example, in the hazard identification step there has been little discrimination among animal carcinogens with respect to mechanism of action or the epidemiology experience. In the dose-response portion, rarely is the range of "plausible" estimated risks presented. Physiologically based pharmacokinetic (PB-PK) models should be used to understand the difference between the tissue doses and the administered dose, as well as the difference in target tissue concentrations of the toxicant between rodents and humans. Biologically-based models like the Moolgavkar-Knudson-Venzon (MKV) should be developed and used, when appropriate. The exposure assessment step can be significantly improved by using more sensitive and specific sampling and analytical methods, more accurate exposure parameters, and computer models that can account for complex environmental factors. Whenever possible, model predictions of exposure and uptake should be validated by biological monitoring of exposed persons (urine, blood, adipose) or by field measurements of plants, soil, fish, air, or water. In each portion of an assessment, the weight of evidence approach should be used to identify the most defensible value. In the risk characterization, the best estimate of the potential risk as well as the highest plausible risk should be presented. Future assessments would be much improved if quantitative uncertainty analyses were conducted. Procedures are currently available for making future assessments. By correcting some of these shortcomings in how health risk assessments have been conducted, scientists and risk managers should be better able to identify scientifically appropriate ambient air standards and emission limits.     

Rodent sperm analysis in field-based ecological risk assessment: pilot study at Ravenna army ammunition plant,Ravenna, Ohio

Ecological risk assessment (ERA) guidance recommends that field-truthing efforts proceed when modeled hazard quotients (HQs) suggest that toxicological effects are occurring to site receptors. To date, no field methods have been proposed by the regulatory community that can lead to definitive determinations of acceptable or unacceptable risk for birds and mammals, the two terrestrial classes of receptors that are commonly assessed using the HQ method. This paper describes rodent sperm analysis (RSA) as a viable method to be applied in the field at sites with historical contamination. RSA is capable of detecting biological differences that bear on reproduction, a highly regarded toxicological endpoint of concern in USEPA Superfund-type ERAs. The results of RSA's first application at a study site are reported and discussed. The paper also provides the rationale for RSA's efficacy in the context of Superfund and other environmental cleanup programs, where limited time and money are available to determine and evaluate the field condition.     

The utility of behavioral studies for aquatic toxicology testing: A meta-analysis

Behavioral responses have been applied for decades as tools for aquatic toxicity testing, but have received far less attention than studies assessing lethality, development or reproduction. With improved visual and non-visual assessment tools and increased knowledge of the importance of behavior for organism health and fitness, interest in behavioral analysis has increased in recent years. However, to our knowledge there has never been a quantitative assessment of the available techniques for organismal toxicity testing, so it is not clear whether behavioral studies represent valuable additions to environmental monitoring. We performed a meta-analysis comparing the relative sensitivities and average durations of behavioral studies to those assessing acute lethality, development and reproduction. Results demonstrate that the average duration of behavioral studies is consistently less than developmental or reproductive studies, and that behavioral endpoints are generally more sensitive than those assessing development or reproduction. We found effect sizes to be lower but power to be higher in behavioral and reproductive studies compared to studies assessing development, which likely relates to low sample sizes commonly used in developmental studies. Overall, we conclude that behavioral studies are comparatively fast and sensitive, and therefore warrant further attention as tools for assessing the toxicological effects of environmental contaminants. We suggest that research aimed at developing and optimizing techniques for behavioral analysis could prove extremely useful to the field of toxicology, but that future work must be directed at determining what specific behaviors are most sensitive to various classes of contaminants, and at understanding the relevance of changes to discrete behaviors for influencing organismal and population-level health and fitness.     

A pond mesocosm study to determine direct and indirect effects of lindane on a natural zooplankton community

We assessed the threshold concentrations for toxic effects by lindane on a zooplankton community using mesocosms in a natural pond. Enclosures (1000 litres) were treated to give mean concentrations of 0, 2, 6, 12, 18, 24, and 50 microg litre(-1) over a test period of 39 days. Larvae of the phantom midge Chaoborus flavicans showed a high susceptibility to lindane and were virtually eliminated from enclosures with > or =12 microg litre(-1) 4 days after application. Populations of cyclopoid nauplii (Eucyclops serrulatus) were reduced at a lindane concentration of 2 microg litre(-1) and showed high mortality after 11 days exposure to > or =6 g litre(-1). No lindane-induced effects could be seen in the cladoceran species Daphnia longispina and Chydorus sphaericus. Rotifer species were probably not directly affected by lindane; however loss of the principal predator Chaoborus was accompanied by an increase in the numbers of Asplanchna priodonta. A simultaneous decrease in Keratella quadrata possibly reflected predation since its decline showed no dose-response relationship with lindane and it is among the major prey of Asplanchna. Such complex secondary effects, occurring through trophic interactions between a predator and two co-occurring prey, would not have been predicted from single-species toxicity tests. These, and effects on cyclopoid populations that occurred predominantly through the mortality of nauplii, demonstrate the value of toxicological studies on natural communities. We conclude that a combination of laboratory and field investigations, coupled with mono-species and community assessments, provide the best route for understanding the effects of toxicants such as lindane for regulatory purposes.     

Comment on “Assessment of Crop Loss from Ozone”

Abstract

A mathematical model is proposed for assessing health risk rates of fluctuating concentrations. Each time-averaged concentration may be regarded as a dose that, when applied to the dose-response curve, produces a risk of an adverse effect. A theoretical derivation shows that the dose-response pattern is a cumulative lognormal curve because of the diversity of the individuals in the exposed population. Similarly, the concentration pattern is a log-normal distribution because of the diversity of emission sources and dispersive processes. The health risk is produced by the overlapping of the right tail of the concentration distribution and the left tail of the dose-response curve. The evaluation of the joint probability in this region has been performed by numerical integration by computer in terms of two generalized parameters. One represents the geometric standard deviation of the concentration distribution relative to that of the dose-response curve, and the other represents the distance between the geometric mean concentration and the concentration producing an adverse response in 50% of the exposed population. These results are presented graphically and in tabular form. If the two parameters of the dose-response curve are known, the health risk of the concentration pattern may be calculated conveniently for any geometric mean and geometric standard deviation values.     

Selection of non-dioxin-like PCBs for in vitro testing on the basis of environmental abundance and molecular structure

The non-dioxin-like polychlorinated biphenyls (NDL-PCBs) constitute the major proportion of PCBs found in food and human tissues. It is important to improve our understanding of the toxicity, environmental and human risks associated with the NDL-PCBs, since their toxicology is incompletely characterized and a human health risk assessment is required. This paper discusses the selection of a training set of 20 tri- to hepta-chlorinated biphenyls, PCBs 19,28,47,51,52,53,74,95,100,101,104,118,122,128,136,138,153,170,180, and 190. Suggested for comprehensive screening using in vitro assays to identify critical mechanisms of toxicological action. The selected PCBs form a balanced basis for developing of quantitative structure-activity relationship (QSAR) models for prediction of physicochemical and toxicological properties of non-tested PCB congeners. Chemical and physical properties, environmental abundance and toxicological activities of the congeners were considered during the selection process. A complementary set of PCBs, a reference set, was selected using D-optimal onion design including PCBs 18,20,28,30,37,40,50,54,60,77,82,99,122,132,153,161,170,188,192, and 193. Congeners of this set are well suited for validation of QSAR models developed using the training set. For visualization of the chemical diversity of environmentally abundant PCBs and congeners of the training and reference sets, principal component analysis (PCA) was used. Statistical molecular design was used to verify the structural representation. As a reference structure for dioxin-like PCBs, PCB 126 was added in the training set. The selected set of NDL-PCBs is proposed for use in toxicological testing programs to provide rational basis for risk assessment of the NDL-PCBs.     

On the translation of uncertainty from toxicokinetic to toxicodynamic models--the TCDD example

When estimating human health risks from exposure to TCDD using toxicokinetic and toxicodynamic models, it is important to understand how model choice and assumptions necessary for modeling add to the uncertainty of risk estimates. Several toxicokinetic models have been proposed for the risk assessment of dioxins, in particular the elimination kinetics in humans has been a matter of constant debate. For a long time, a simple linear elimination kinetics has been common choice. Thus, it was used for the statistical analysis of the largest occupationally exposed cohort, the German Boehringer cohort. We challenge this assumption by considering, amongst others, a nonlinear modified Michaelis-Menten-type elimination kinetics, the so-called Carrier kinetics. Using the area under the lipid TCDD concentration time curve as dose metrics, we model the time to cancer-related death using the Cox proportional hazards model as toxicodynamic model. This risk assessment set-up was simulated in order to quantify uncertainty of both the dose (TCDD body burden) and the risk estimates, depending on the use of the kinetic model, variations of carcinogenic effect of TCDD and variations of latency period (lag time). If past exposure is estimated assuming a linear elimination kinetics although a Carrier kinetics actually holds, then high exposures in reality will be underestimated through statistical analysis and low exposures will be overestimated, respectively. This bias will carry over on the estimated individual concentration-time curves and the therefrom derived TCDD dose metric values. Using biased dose values when estimating a dose-response relationship will finally lead to biased risk estimates. The extent of bias and the decrease of precision are quantified in selected scenarios through this simulation approach. Our findings are in concordance with recent results in the field of dioxin risk assessment. They also reinforce the general demand for the scheduled uncertainty assessments in risk analyses.     

The Tools of Environmental Litigation Support: How Environmental Litigation Support Teams Employ a Unique Set of Skills and Tools to Improve the Outcome and Reduce the Cost of Legal Disputes

While the primary goal of environmental investigations is to assess and clean up contaminated properties, significant efforts are also directed towards resolving various matters in legal dispute. Opposing parties often disagree about the cause and timing of contamination and the associated liability and costs for meeting regulatory site closure requirements. Environmental experts are often needed to help resolve such legal disputes with expertise in hydrogeology, toxicology, microbiology, chemistry, engineering, and process safety. These experts, or teams of experts, provide technical approaches to determine the liability and cost apportionment amongst the various potentially responsible parties. Fate and transport models, environmental forensics, and risk assessment help to answer the issues in dispute. Skillful communication of these technical findings is needed to present conclusions to audiences that do not necessarily have technical backgrounds.     

Environmental and biological monitoring of endocrine disrupting chemicals.

Trends toward an increase of adverse health effects on reproductive organs have been reviewed. An urgent need has been recognised to establish validated in vivo and in vitro screening assays to test for hormonal activities of chemicals. Relevant existing OECD guidelines have been reviewed and enhancements of some of these have been identified, mainly to test for estrogenic and androgenic activity of chemicals. The problems connected to monitoring activities are outlined, particularly for ambient and biological monitoring. Indeed, the problem of assessing human exposure to endocrine disrupting chemicals through environmental chemical analysis tends to a very high level of complexity. This has been illustrated through the example of one single subclass of endocrine disrupting compounds (EDCs), the organohalogen compounds. Valid biological markers are also needed to be effectively used in epidemiological studies and risk assessment. A multidisciplinary approach and the collaboration among experts in the field of clinical biochemistry, toxicology, and epidemiology is required.     

Ozone Air Quality Models

Abstract

The field of ozone air quality modeling, or as it is commonly referred to, photochemical air quality modeling, has undergone rapid change in recent years. Improvements in model components, as well as in methods of interpreting model performance, have contributed to this change. Attendant with this rapid change has been a growing need for those developing and using air quality models and policy makers to have a common understanding of the use and role of models in the decision making process. This Critical Review highlights recent advances and continuing problem areas in photochemical air quality modeling. Emphasis is placed on the components and input data for such models, model performance evaluation, and the implications for their use in regulatory decisions.     

A new methodology development for the regulatory forecasting of PM10. Application in the Greater Athens Area,Greece

The paper introduces a new methodology for the prediction of daily PM10 concentrations, in line with the regulatory framework introduced through the EU Directive 2008/50/EC. The proposed approach is based on the efficient utilisation of the data collected over short time intervals (hourly) rather than the daily values used to derive the daily regulatory threshold. It is sufficiently simple and easily applicable in operational forecasting systems with the ability to accept as inputs both historical data and exogenous paraeters, such as meteorological variables. The application of the proposed methodology is demonstrated using data from five monitoring stations of air pollutants located in Athens, over a five year period (2000–2004) as well as compatible meteorological data from the NCEP (National Centers for Environmental Protection). A set of different models have been tested at the same time to reveal the effectiveness of the proposed approach, both univariate and multivariate, and linear and non-linear models. The analysis of all examined datasets has shown conclusive evidence that the introduction of the newly developed procedure which utilises data collected over a shorter horizon can significantly increase the forecasting ability of any developed model using daily historic PM10 data, under all examined metrics.     

Evaluating the environmental fate of atrazine in France

Atrazine is used in large quantities in U.S. and European countries as a weed-control agent. As a result, numerous data on its environmental fate and hazards have been published. Analysis of the literature shows that this herbicide can be found with appreciable concentrations in groundwaters, rivers, lakes, and estuaries. This contamination principally results from leaching and runoff processes. Atrazine can also pollute fog and rain due to its release into the atmosphere through spray applications. This large amount of information constitutes a very attractive basis for assessing the simulation performances of environmental fate models. In this context, CHEMFRANCE, a regional fugacity model level III which calculates the environmental distribution of organic chemicals in twelve defined regions of France has been used to estimate the environmental fate of atrazine. The calculated values are comparable with field and laboratory results. Therefore, CHEMFRANCE can be considered as a useful tool for simulating the environmental fate of this agrochemical.     

Using plant biomonitors and flux modelling to develop O3 dose-response relationships in Catalonia

We used tobacco Bel-W3 biomonitoring data and ozone flux modelling (WINDEP model) with the aim of developing the absorbed dose-response relationship, and comparing this approach with the most commonly used AOT40 (the sum of hourly ozone concentrations above a cut-off of 40 ppb during daylight hours, when global radiation exceeds 50 W m(-2)) in the estimation of exposure-damage curves. Leaf damage values were more related to OAD(15 days, potential) (potential ozone absorbed dose calculated over 15 consecutive days) than to AOT40 in all the studied stations. An OAD(15 days, potential) of 180 mg m(-2) was found to be the threshold for damage to the most sensitive species in this region under well watered conditions. The results show the applicability of the flux approach for risk assessment at the local scale, the improvement of the ozone damage estimation when the potential absorbed dose is modelled and used instead of just the ozone exposure, and finally, the possibilities opened by the use of biomonitoring networks.     

Modelling radionuclide distribution and transport in the environment

Mathematical models of radionuclide distribution and transport in the environment have been developed to assess the impact on people of routine and accidental releases of radioactivity from a variety of nuclear activities, including: weapons development, production, and testing; power production; and waste disposal. The models are used to estimate human exposures and doses in situations where measurements have not been made or would be impossible or impractical to make. Model results are used to assess whether nuclear facilities are operated in compliance with regulatory requirements, to determine the need for remediation of contaminated sites, to estimate the effects on human health of past releases, and to predict the potential effects of accidental releases or new facilities. This paper describes the various applications and types of models currently used to represent the distribution and transport of radionuclides in the terrestrial and aquatic environments, as well as integrated global models for selected radionuclides and special issues in the fields of solid radioactive waste disposal and dose reconstruction. Particular emphasis is placed on the issue of improving confidence in the model results, including the importance of uncertainty analysis and of model verification and validation.