Challenges and Research Needs for Risk Assessment of Pesticides for Registration in Africa

Risk assessment is necessary for registration and risk management of new pesticides. The aim of this article is to discuss challenges that risk assessors in Africa face when conducting risk assessment of pesticides. Risk assessment requires toxicity assessment, environmental fate studies, and the use of models for occupational, dietary, residential, and environmental exposure assessments. Toxicity studies are very costly with the result that toxicity data used to register pesticides in Africa are often sourced from northern hemisphere countries. Assessors also often use exposure modeling results from the northern hemisphere. This is not an ideal approach as occupational exposure is influenced by agricultural practices, climatic conditions, and other factors. Furthermore, residential exposure models require time-location-activity information, exposure factors, and toxicokinetic rate constants for particular pesticides. Dietary exposure assessment needs accurate and comprehensive local food consumption data. Authorities in African countries should therefore generate the required data, despite these being very costly and tedious. Authorities should also provide guidance on the type of models and standard scenarios for estimating predicted environmental concentrations in various environmental compartments. It is recommended that higher educational institutions in Africa should incorporate risk assessment in general and pesticide toxicity and exposure models in particular in their curricula.     

Applying a weed risk assessment approach to GM crops

Current approaches to environmental risk assessment of genetically modified (GM) plants are modelled on chemical risk assessment methods, which have a strong focus on toxicity. There are additional types of harms posed by plants that have been extensively studied by weed scientists and incorporated into weed risk assessment methods. Weed risk assessment uses robust, validated methods that are widely applied to regulatory decision-making about potentially problematic plants. They are designed to encompass a broad variety of plant forms and traits in different environments, and can provide reliable conclusions even with limited data. The knowledge and experience that underpin weed risk assessment can be harnessed for environmental risk assessment of GM plants. A case study illustrates the application of the Australian post-border weed risk assessment approach to a representative GM plant. This approach is a valuable tool to identify potential risks from GM plants.     

Assessing the Risk of Herbicides to Terrestrial Non-Target Plants Using Higher-Tier Studies

Risk assessment for non-target plants is based on single species phytotoxicity tests. This approach may not reflect relevant ecological processes in terrestrial ecosystems. The current risk assessment scheme is based on endpoints measured at the species level and the assessment of ecological effects relies on the extrapolation from one species to another or from a single species to a community. This extrapolation contains many uncertainties that may be reduced by adopting more realistic testing approaches. However, currently higher-tier plant studies are not obligatory in herbicide risk assessment. We reviewed the published literature and found that potential higher-tier approaches for terrestrial non-target plants are extremely limited. Sixteen studies were found that assessed the effects of herbicides on non-target plants by performing microcosms, mesocosms, or field studies. These studies showed that microcosms might provide useful data and help to reduce uncertainties associated with single-species tests. However, due to the limited number of available studies, much work is required to develop appropriate testing methods for regulatory processes. In addition, field experiments are necessary to establish baseline knowledge concerning the effects of herbicides on natural plant communities and to compare data generated in tiered testing approaches with data obtained from natural systems.     

Genotoxicity risk assessment: a proposed classification strategy

Recent advances in genetic toxicity (mutagenicity) testing methods and in approaches to performing risk assessment are prompting a renewed effort to harmonize genotoxicity risk assessment across the world. The US Environmental Protection Agency (EPA) first published Guidelines for Mutagenicity Risk Assessment in 1986 that focused mainly on transmissible germ cell genetic risk. Somatic cell genetic risk has also been a risk consideration, usually in support of carcinogenicity assessments. EPA and other international regulatory bodies have published mutagenicity testing requirements for agents (pesticides, pharmaceuticals, etc.) to generate data for use in genotoxicity risk assessments. The scheme that follows provides a proposed harmonization approach in which genotoxicity assessments are fully developed within the risk assessment paradigm used by EPA, and sets out a process that integrates newer thinking in testing battery design with the risk assessment process. A classification strategy for agents based on inherent genotoxicity, dose-responses observed in the data, and an exposure analysis is proposed. The classification leads to an initial level of concern for genotoxic risk to humans. A total risk characterization is performed using all relevant toxicity data and a comprehensive exposure evaluation in association with the genotoxicity data. The result of this characterization is ultimately used to generate a final level of concern for genotoxic risk to humans. The final level of concern and characterized genotoxicity risk assessment are communicated to decision makers for possible regulatory action(s) and to the public.     

Genotoxicity risk assessment: a proposed classification strategy

Recent advances in genetic toxicity (mutagenicity) testing methods and in approaches to performing risk assessment are prompting a renewed effort to harmonize genotoxicity risk assessment across the world. The US Environmental Protection Agency (EPA) first published Guidelines for Mutagenicity Risk Assessment in 1986 that focused mainly on transmissible germ cell genetic risk. Somatic cell genetic risk has also been a risk consideration, usually in support of carcinogenicity assessments. EPA and other international regulatory bodies have published mutagenicity testing requirements for agents (pesticides, pharmaceuticals, etc.) to generate data for use in genotoxicity risk assessments. The scheme that follows provides a proposed harmonization approach in which genotoxicity assessments are fully developed within the risk assessment paradigm used by EPA, and sets out a process that integrates newer thinking in testing battery design with the risk assessment process. A classification strategy for agents based on inherent genotoxicity, dose-responses observed in the data, and an exposure analysis is proposed. The classification leads to an initial level of concern for genotoxic risk to humans. A total risk characterization is performed using all relevant toxicity data and a comprehensive exposure evaluation in association with the genotoxicity data. The result of this characterization is ultimately used to generate a final level of concern for genotoxic risk to humans. The final level of concern and characterized genotoxicity risk assessment are communicated to decision makers for possible regulatory action(s) and to the public.     

A Novel Approach to Determining a Population-Level Threshold in Ecological Risk Assessment: A Case Study of Zinc

A novel approach to population-level assessment was applied in order to demonstrate its utility in estimating and managing the risk of zinc in a water environment. Much attention has been paid to population-level risk assessment, but there have been no attempts to determine a “safe” population-level concentration as an environmental criterion. Based on the published results of toxicity tests for various species, we first theoretically derived a threshold concentration at which a population size is unchanged due to the adverse effects of zinc exposure. To derive a zinc concentration that will protect populations in natural environments, we adopted the concept of species sensitivity distribution. Assuming the threshold concentrations of a set of species are log-normally distributed, we calculated the 95% protection level of zinc (PHC₅ :population-level hazardous concentration of 5% of species), which is 107 μg/L. Meanwhile, the 95% protection criterion (HC₅) based on conventional individual-level chronic toxicity, was calculated to be 14.6 μg/L. The environmentally “safe” concentration for a population-level endpoint is about 7 times greater than that for an individual-level endpoint. The proposed method provides guidance for a pragmatic approach to population-level ecological risk assessment and the management of chemicals.     

Probabilistic Risk Assessment and Risk Mapping of Sediment Metals in Sydney Harbour Embayments

Sediment metal concentrations in embayments of Sydney Harbour, acquired from the literature and from samples collected for this study, were used to generate contaminant probability density distributions using AQUARISK. The sediment metal concentrations often exceeded Australia's interim sediment quality guidelines. Similarly, estuarine spiked sediment toxicity test literature provided adverse biotic effects concentration data to generate species sensitivity distributions using AQUARISK. Although the harbor is subject to other inorganic and organic contamination, we have used sediment metals to demonstrate an approach for ecological risk mapping and environmental management prioritization. Sufficient spiked sediment toxicity test data were found for only three metals—Cd, Cu, and Zn—and some tests were likely to overestimate toxicity. The estimates of the hazardous concentration to 5% of species (the 50th percentile of the 95% species protection level) were 5, 12, and 40 mg/kg DW of total sediment metal for Cd, Cu, and Zn, respectively. These values were generally low when compared with the interim sediment quality guidelines due to the overestimation of toxic effects in the literature data. The parameters for the species sensitivity distributions have been combined with the measured sediment metal concentrations in Homebush Bay to generate risk maps of the estimated species impact for each metal as well as for all three metals collectively assuming proportional additivity. This has demonstrated the utility of comparing contaminants on a consistent scale—ecological risk.     

Ecological theory meets soil ecotoxicology: Challenge and chance

The degradation of soils due to various anthropogenic stress factors is alarming. Although chemicals are a major reason for soil degradation, most ecologists are not interested in studying such effects. We try to wake their interest by addressing a number of unsolved soil ecotoxicological problems that are related to disturbance ecology, biodiversity, ecosystem functioning and modelling. Features distinguishing chemical from natural stress render promising new aspects in disturbance ecology. Ecotoxicological studies are ideal models of disturbance, particularly regarding frequency, intensity or multitude of stress. Patterns of secondary succession after a major chemical damage can directly be related to the intermediate disturbance hypothesis. More knowledge on altered life history patterns following stress could support both evolutionary ecology and risk assessment. We raise the question if inherent resource competition makes communities more vulnerable to stress. Three aspects of ecotoxicological risk assessment are introduced: (1) exposure and bioavailability, which is directly connected to environmental heterogeneity; (2) tests on ecosystem functioning, suffering from major drawbacks; and (3) modelling. Here, promising approaches exist but need substantial input for being applicable to soils. Ecological modelling should put more emphasis on simulating both natural and chemical disturbances, including behavioural aspects and environmental variability. Finally, research needs for ecological risk assessment in soils are derived such as a simple system to assess the impact of chemicals on soil biodiversity, the inclusion of behavioural changes of keystone species or the consideration of density-dependent effects. Common research efforts of basic ecologists and soil ecotoxicologists could render a lot of mutual benefits.     

Extrapolations are the Achilles heel of risk assessment

This Reflections article considers the problems associated with the various extrapolations that are required for the estimation of human cancer risks from exposure to environmental carcinogens at low doses. These include extrapolation between species (particularly rodent to human), from responses at high doses to those at low doses, and among different stages of life. Reductions in uncertainty in risk estimates are closely coupled to the ability to conduct reliable extrapolations. The best way forward appears to be the use of data on mechanisms of carcinogenesis to develop bioindicators of responses related to the pathway to tumor formation. Such an approach is proposed based on the phenotypes represented by the six acquired characteristics forming the Hanahan-Weinberg model for carcinogenesis (The Hallmarks of Cancer). In addition, approaches can be established that use the Hanahan-Weinberg model as the basis for the collection and/or analysis of microarray or similar data. The reduction in reliance on default options and safety factors in the risk assessment process is a real possibility.     

Review of risk assessment systems of IAS in Europe and introducing the German–Austrian Black List Information System (GABLIS)

We give a mini-review of existing European risk assessment procedures and present a newly developed and tested risk assessment tool for invasive alien species (IAS) in Germany and Austria, the “German–Austrian Black List Information System” (GABLIS). Based on the analysis of existing European national risk assessment systems, we analyse and discuss: the assessment criteria used; which impacts of IAS (biodiversity, economy) have been considered; for which taxonomic groups has the assessment been designed and tested; how many and which list categories have been used; and, the status of the assessment, i.e. legally binding or advisory. We found that the application of risk assessment systems in Europe started belatedly, however recently a considerable number of assessment systems have been developed and tested. These systems encompass a wide range of purposes and approaches, and so far, no common standard on the aspects mentioned above has been emerged.GABLIS has been developed as a trans-national and taxonomically universal risk assessment system, which takes into account solely the detrimental effects of alien species on biodiversity. We describe which kinds of impacts are considered and how the thresholds have been scaled. We present the structure of the list categories, and we discuss the necessary underlying data for assessment, the assessment criteria and their scaling, and the assessment procedure. Five basic and six complementary criteria are used to assess the alien species’ impact. GABLIS includes three main list categories (White List, Grey List, and Black List).We discuss the practicability of GABLIS by presenting the assessment results of a model taxon (fish), and by presenting the assessment protocol for a vascular plant species. We discuss the necessary data quality for assessments, and the factors which account for differences in the assessments between both countries. We also report on experiences gained in assessments (e.g., average time necessary for assessments). The lessons learnt are discussed in the national and European political context of IAS management.Finally, we explore the strengths and caveats of this approach in the context of national policy on IAS in Germany and Austria and the ongoing European political initiatives. GABLIS is intended to serve as a comprehensive, flexible, but robust risk assessment tool for Central Europe. Being a trans-national risk assessment tool, GABLIS also tests principles, which might contribute valuable insights for a future overall strategy against IAS in Europe.     

Risk assessment issues in breast cancer

Breast cancer is the most common malignancy affecting women, and its incidence has been increasing in many countries. The aetiology of breast cancer is poorly understood, so there is concern as to which factors in our environment or lifestyle are responsible for the increase. There is a need for reliable risk assessment, which involves the steps of hazard identification, hazard evaluation, exposure evaluation and risk estimation. Short-term laboratory tests and long-term tests in animals are useful for priority-setting, but quantitative human risk assessment should preferably involve observations of humans. Epidemiological studies vary in the degree of reliance that can be placed on their results. The main types of epidemiological investigation are illustrated by recent examples from the literature on breast cancer. Careful judgement is required in assessing whether any association between a factor and a disease is likely to be causal. The injectable contraceptive, depot medroxyprogesterone acetate (DMPA, ‘Depo-Provera’), has been controversial because it caused malignant mammary tumours in beagle dogs. Two recent case-control studies found no overall association between DMPA and the risk of breast cancer in women. There was some evidence of increased risk in certain sub-groups of women, which could be interpreted with more confidence if there were a better understanding of the biology of human breast cancer. Nevertheless, the results do not support the prediction from beagle experiments that DMPA might increase the overall risk of breast cancer.     

virtualspecies,an R package to generate virtual species distributions

virtualspecies is a freely available package for R designed to generate virtual species distributions, a procedure increasingly used in ecology to improve species distribution models. This package combines the existing methodological approaches with the objective of generating virtual species distributions with increased ecological realism. The package includes 1) generating the probability of occurrence of a virtual species from a spatial set of environmental conditions (i.e. environmental suitability), with two different approaches; 2) converting the environmental suitability into presence–absence with a probabilistic approach; 3) introducing dispersal limitations in the realised virtual species distributions and 4) sampling occurrences with different biases in the sampling procedure. The package was designed to be extremely flexible, to allow users to simulate their own defined species–environment relationships, as well as to provide a fine control over every simulation parameter. The package also includes a function to generate random virtual species distributions. We provide a simple example in this paper showing how increasing ecological realism of the virtual species impacts the predictive performance of species distribution models. We expect that this new package will be valuable to researchers willing to test techniques and protocols of species distribution models as well as various biogeographical hypotheses.     

Evolution of simple sequence repeat-mediated phase variation in bacterial genomes

Mutability as mechanism for rapid adaptation to environmental challenge is an alluringly simple concept whose apotheosis is realized in simple sequence repeats (SSR). Bacterial genomes of several species contain SSRs with a proven role in adaptation to environmental fluctuations. SSRs are hypermutable and generate reversible mutations in localized regions of bacterial genomes, leading to phase variable ON/OFF switches in gene expression. The application of genetic, bioinformatic, and mathematical/computational modeling approaches are revolutionizing our current understanding of how genomic molecular forces and environmental factors influence SSR-mediated adaptation and led to evolution of this mechanism of localized hypermutation in bacterial genomes.     

Assessing environmental risks of transgenic plants

By the end of the 1980s, a broad consensus had developed that there were potential environmental risks of transgenic plants requiring assessment and that this assessment must be done on a case-by-case basis, taking into account the transgene, recipient organism, intended environment of release, and the frequency and scale of the intended introduction. Since 1990, there have been gradual but substantial changes in the environmental risk assessment process. In this review, we focus on changes in the assessment of risks associated with non-target species and biodiversity, gene flow, and the evolution of resistance. Non-target risk assessment now focuses on risks of transgenic plants to the intended local environment of release. Measurements of gene flow indicate that it occurs at higher rates than believed in the early 1990s, mathematical theory is beginning to clarify expectations of risks associated with gene flow, and management methods are being developed to reduce gene flow and possibly mitigate its effects. Insect pest resistance risks are now managed using a high-dose/refuge or a refuge-only strategy, and the present research focuses on monitoring for resistance and encouraging compliance to requirements. We synthesize previous models for tiering risk assessment and propose a general model for tiering. Future transgenic crops are likely to pose greater challenges for risk assessment, and meeting these challenges will be crucial in developing a scientifically coherent risk assessment framework. Scientific understanding of the factors affecting environmental risk is still nascent, and environmental scientists need to help improve environmental risk assessment.     

Integrated Human and Ecological Risk Assessment: A Case Study of Organophosphorous Pesticides in the Environment

This study was chosen as an example of integrated risk assessment because organophosphorous esters (OPs) share exposure characteristics for different species, including human beings and because a common mechanism of action can be identified. The “Framework for the integration of health and ecological risk assessment” is being tested against a deterministic integrated environmental health risk assessment for OPs used in a typical farming community. It is argued that the integrated approach helps both the risk manager and the risk assessor in formulating a more holistic approach toward the risk of the use of OP-esters. It avoids conclusions based on incomplete assessments or on separate assessments. The database available can be expanded and results can be expressed in a more coherent manner. In the integrated exposure assessment of OPs, the risk assessments for human beings and the environment share many communalities with regards to sources and emissions, distribution routes and exposure scenarios. The site of action of OPs, acetylcholinesterase, has been established in a vast array of species, including humans. It follows that in the integrated approach the effects assessment for various species will show communalities in reported effects and standard setting approaches. In the risk characterization, a common set of evidence, common criteria, and common interpretations of those criteria are used to determine the cause of human and ecological effects that co-occur or are apparently associated with exposure to OPs. Results of health and ecological risk assessments are presented in a common format that facilitates comparison of results. It avoids acceptable risk conclusions with regard to the environment, which are unacceptable with regard to human risk and vice versa. Risk managers will be prompted to a more balanced judgement and understanding and acceptance of risk reduction measures will be facilitated.     

Characterizing,Propagating, and Analyzing Uncertainty in Life‐Cycle Assessment: A Survey of Quantitative Approaches

Life‐cycle assessment (LCA) practitioners build models to quantify resource consumption, environmental releases, and potential environmental and human health impacts of product systems. Most often, practitioners define a model structure, assign a single value to each parameter, and build deterministic models to approximate environmental outcomes. This approach fails to capture the variability and uncertainty inherent in LCA. To make good decisions, decision makers need to understand the uncertainty in and divergence between LCA outcomes for different product systems. Several approaches for conducting LCA under uncertainty have been proposed and implemented. For example, Monte Carlo simulation and fuzzy set theory have been applied in a limited number of LCA studies. These approaches are well understood and are generally accepted in quantitative decision analysis. But they do not guarantee reliable outcomes. A survey of approaches used to incorporate quantitative uncertainty analysis into LCA is presented. The suitability of each approach for providing reliable outcomes and enabling better decisions is discussed. Approaches that may lead to overconfident or unreliable results are discussed and guidance for improving uncertainty analysis in LCA is provided.     

Evaluation of Ecotoxicological Field Studies for Authorization of Plant Protection Products in Europe

An increasing number of ecotoxicological field studies are being submitted in the European Union procedure for authorization of pesticides. Although there is some guidance on how these studies can be used for risk assessment, not all aspects of field tests are covered and the guidance differs per type of test and per non-target group. To facilitate a more uniform approach by the regulatory authorities in the EU, a basic scheme is proposed with qualitative tools to: (i) assess the scientific reliability of individual field tests, and (ii) to assess the usefulness of field tests for regulatory risk assessment of the pesticide under registration. In this way, the treatment, evaluation, and the mutual comparability of field data for regulatory purposes is harmonized. It thereby provides a more consistent foundation for further risk assessment.     

Global habitat suitability for framework-forming cold-water corals

Predictive habitat models are increasingly being used by conservationists, researchers and governmental bodies to identify vulnerable ecosystems and species' distributions in areas that have not been sampled. However, in the deep sea, several limitations have restricted the widespread utilisation of this approach. These range from issues with the accuracy of species presences, the lack of reliable absence data and the limited spatial resolution of environmental factors known or thought to control deep-sea species' distributions. To address these problems, global habitat suitability models have been generated for five species of framework-forming scleractinian corals by taking the best available data and using a novel approach to generate high resolution maps of seafloor conditions. High-resolution global bathymetry was used to resample gridded data from sources such as World Ocean Atlas to produce continuous 30-arc second (～1 km(2)) global grids for environmental, chemical and physical data of the world's oceans. The increased area and resolution of the environmental variables resulted in a greater number of coral presence records being incorporated into habitat models and higher accuracy of model predictions. The most important factors in determining cold-water coral habitat suitability were depth, temperature, aragonite saturation state and salinity. Model outputs indicated the majority of suitable coral habitat is likely to occur on the continental shelves and slopes of the Atlantic, South Pacific and Indian Oceans. The North Pacific has very little suitable scleractinian coral habitat. Numerous small scale features (i.e., seamounts), which have not been sampled or identified as having a high probability of supporting cold-water coral habitat were identified in all ocean basins. Field validation of newly identified areas is needed to determine the accuracy of model results, assess the utility of modelling efforts to identify vulnerable marine ecosystems for inclusion in future marine protected areas and reduce coral bycatch by commercial fisheries.     

V.PhyloMaker: an R package that can generate very large phylogenies for vascular plants

We present V.PhyloMaker, a freely available package for R designed to generate phylogenies for vascular plants. The mega‐tree implemented in V.PhyloMaker (i.e. GBOTB.extended.tre), which was derived from two recently published mega‐trees and includes 74 533 species and all families of extant vascular plants, is the largest dated phylogeny for vascular plants. V.PhyloMaker can generate phylogenies for very large species lists (the largest species list that we tested included 314 686 species). V.PhyloMaker generates phylogenies at a fast speed, much faster than other phylogeny‐generating packages. Our tests of V.PhyloMaker show that generating a phylogeny for 60 000 species requires less than six hours. V.PhyloMaker includes an approach to attach genera or species to their close relatives in a phylogeny. We provide a simple example in this paper to show how to use V.PhyloMaker to generate phylogenies.