Quantitative risk assessment of skin sensitising pesticides: Clinical and toxicological considerations.

Like many other consumer and occupational products, pesticide formulations may contain active ingredients or co-formulants which have the potential to cause skin sensitisation. Currently, there is little evidence they do, but that could just reflect lack of clinical investigation. Consequently, it is necessary to carry out a safety evaluation process, quantifying risks so that they can be properly managed. A workshop on this topic in 2022 discussed how best to undertake quantitative risk assessment (QRA) for pesticide products, including learning from the experience of industries, notably cosmetics, that already undertake such a process routinely. It also addressed ways to remedy the matter of clinical investigation, even if only to demonstrate the absence of a problem. Workshop participants concluded that QRA for skin sensitisers in pesticide formulations was possible, but required careful justification of any safety factors applied, as well as improvements to the estimation of skin exposure. The need for regulations to stay abreast of the science was also noted. Ultimately, the success of any risk assessment/management for skin sensitisers must be judged by the clinical picture. Accordingly, the workshop participants encouraged the development of more active skin health monitoring amongst groups most exposed to the products.

Guidance on the assessment of exposure of operators, workers, residents and bystanders in risk assessment of plant protection products.

This guidance is designed to assist risk assessors and applicants when quantifying potential non-dietary, systemic exposures as part of regulatory risk assessment for plant protection products (PPPs). It is based on the Scientific Opinion on 'Preparation of a Guidance Document on Pesticide Exposure Assessment for Workers, Operators, Residents and Bystanders' developed by the EFSA Panel on Plant Protection Products and their Residue (PPR) in 2010. Highlighting some inconsistencies between the approaches adopted by regulatory authorities, the PPR Panel proposed a number of changes to the practices in use (i.e. use of deterministic methods for individual PPPs; need to perform an acute risk assessment for PPPs that are acutely toxic; use of appropriate percentile for acute or longer term risk assessments). In the first version of the guidance, issued in 2014, several scenarios for outdoor uses were included, with an annexed calculator, as well as recommendations for further research. The guidance has been updated in 2021 with the inclusion of additional scenarios and revision of default values, on the basis of the evaluation of additional evidence. To support users in performing the assessment of exposure and risk, an online calculator, reflecting the guidance content, has been further developed.

A quantitative risk assessment for skin sensitizing plant protection products: Linking derived No-Effect levels (DNELs) with agricultural exposure models.

Chemical skin sensitizers produce allergic contact dermatitis, which is one of the most frequent occupational diseases associated with chemical exposures. Skin exposure is the major route of exposure when using plant protection products (PPPs). Therefore, skin sensitization is an important factor to be addressed during the regulatory risk assessment of PPPs. The main regulatory decision criterion considered when performing risk assessment for skin sensitizers is the dose applied. The equally important criteria "potency of the substance" is insufficiently considered by two potency categories as potency may vary up to five orders of magnitude. "Frequency of exposure" to the skin sensitizer is not considered at all. Consequently, an improved risk assessment methodology is essential to adequately assess health risks from skin sensitizers, especially for agricultural operators using PPPs. A quantitative risk assessment (QRA) approach for addressing PPPs sensitizing potential is proposed here. This QRA combines a methodology to derive a substance-specific threshold for skin sensitizers, a Derived No-Effect Level (DNEL), and an agricultural exposure model used for assessing chronic health risks of PPPs. The proposed QRA for skin sensitizing PPPs is a clear improvement over current risk assessment to ensure the safe use of skin sensitizers in an occupational context.

Occupational exposure to plant protection products and health effects in Switzerland: what do we know and what do we need to do?

AIMS: There is currently no centralised database on workers' exposures to plant protection products (PPPs) in Switzerland, nor a national register for negative health effects linking them to occupational PPP exposure. This lack of basic data makes it difficult to implement either epidemiological research or prevention campaigns for the agricultural sector. The first objective was to understand the level of information and flow of data on occupational PPP exposures and health effects in the Canton of Vaud, Switzerland. Then, to apply this information to develop recommendations for improving a vigilance system for occupational health effects related to PPP exposure. METHODS: A mapping study and semistructured stakeholder interviews were conducted to better understand the flow of data on occupational PPP exposures and health effects. A clinical records investigation of workers occupationally exposed to PPPs was undertaken to understand the magnitude of this potential problem. Finally, a workshop brought together relevant stakeholders to discuss recommendations for the way forwards. RESULTS: A lack of data on PPP exposures and associated health effects was revealed. This highlighted important knowledge gaps at different levels of the current institutional information flow system. We found that although there were numerous stakeholders that worked efficiently in their own mandate, there was a clear need for increased collaboration and coordination in order to make use of existing data to promote safer PPP use among agricultural workers in Switzerland. CONCLUSIONS: Due to increasing evidence of an association between PPP exposure and health effects, increased collaboration between stakeholders is necessary to develop links between the data sources that already exist. Our study was the first to investigate the health effects linked to PPP exposure among the Swiss agricultural population. The recommendations presented in this paper would help promote a safer and healthier agricultural workforce in Switzerland, as well as the population at large.

Towards a more open debate about values in decision-making on agricultural biotechnology.

Regulatory decision-making over the use of products of new technology aims to be based on science-based risk assessment. In some jurisdictions, decision-making about the cultivation of genetically modified (GM) plants is blocked supposedly because of scientific uncertainty about risks to the environment. However, disagreement about the acceptability of risks is primarily a dispute over normative values, which is not resolvable through natural sciences. Natural sciences may improve the quality and relevance of the scientific information used to support environmental risk assessments and make scientific uncertainties explicit, but offer little to resolve differences about values. Decisions about cultivating GM plants will thus not necessarily be eased by performing more research to reduce scientific uncertainty in environmental risk assessments, but by clarifying the debate over values. We suggest several approaches to reveal values in decision-making: (1) clarifying policy objectives; (2) determining what constitutes environmental harm; (3) making explicit the factual and normative premises on which risk assessments are based; (4) better demarcating environmental risk assessment studies from ecological research; (5) weighing the potential for environmental benefits (i.e., opportunities) as well as the potential for environmental harms (i.e., risks); and (6) expanding participation in the risk governance of GM plants. Recognising and openly debating differences about values will not remove controversy about the cultivation of GM plants. However, by revealing what is truly in dispute, debates about values will clarify decision-making criteria.

Environmental change challenges decision-making during post-market environmental monitoring of transgenic crops.

The ability to decide what kind of environmental changes observed during post-market environmental monitoring of genetically modified (GM) crops represent environmental harm is an essential part of most legal frameworks regulating the commercial release of GM crops into the environment. Among others, such decisions are necessary to initiate remedial measures or to sustain claims of redress linked to environmental liability. Given that consensus on criteria to evaluate 'environmental harm' has not yet been found, there are a number of challenges for risk managers when interpreting GM crop monitoring data for environmental decision-making. In the present paper, we argue that the challenges in decision-making have four main causes. The first three causes relate to scientific data collection and analysis, which have methodological limits. The forth cause concerns scientific data evaluation, which is controversial among the different stakeholders involved in the debate on potential impacts of GM crops on the environment. This results in controversy how the effects of GM crops should be valued and what constitutes environmental harm. This controversy may influence decision-making about triggering corrective actions by regulators. We analyse all four challenges and propose potential strategies for addressing them. We conclude that environmental monitoring has its limits in reducing uncertainties remaining from the environmental risk assessment prior to market approval. We argue that remaining uncertainties related to adverse environmental effects of GM crops would probably be assessed in a more efficient and rigorous way during pre-market risk assessment. Risk managers should acknowledge the limits of environmental monitoring programmes as a tool for decision-making.

Monitoring the commercial cultivation of Bt maize in Europe--conclusions and recommendations for future monitoring practice.

Genetically modified (GM) maize expressing the insecticidal protein Cry1Ab from Bacillus thuringiensis (Bt maize) is the only GM crop planted commercially in the European Union (EU). Cultivation in accordance with Directive 2001/18/EC demands post-market environmental monitoring (PMEM) to ensure the detection and prevention of adverse effects on the environment possibly deriving from commercial cultivation. Based on a seminar organized in Berlin, Germany, in April 2008 by the EU-funded Biosafenet project, the present paper reflects on experiences and hurdles faced during the implementation of PMEM for Bt maize. It reviews and reconsiders PMEM programs of Bt maize in view of existing experiences from cultivation, current monitoring activities initiated by Member States and applicants, proposed monitoring strategies and methods as well as potential environmental impacts of cultivation. Future challenges will arise from large-scale and cumulative cultivation of various events. This will demand optimized organization structures for data collation and integration to support further decision-making and management.

Definition and feasibility of isolation distances for transgenic maize cultivation.

A major concern related to the adoption of genetically modified (GM) crops in agricultural systems is the possibility of unwanted GM inputs into non-GM crop production systems. Given the increasing commercial cultivation of GM crops in the European Union (EU), there is an urgent need to define measures to prevent mixing of GM with non-GM products during crop production. Cross-fertilization is one of the various mechanisms that could lead to GM-inputs into non-GM crop systems. Isolation distances between GM and non-GM fields are widely accepted to be an effective measure to reduce these inputs. However, the question of adequate isolation distances between GM and non-GM maize is still subject of controversy both amongst scientists and regulators. As several European countries have proposed largely differing isolation distances for maize ranging from 25 to 800 m, there is a need for scientific criteria when using cross-fertilization data of maize to define isolation distances between GM and non-GM maize. We have reviewed existing cross-fertilization studies in maize, established relevant criteria for the evaluation of these studies and applied these criteria to define science-based isolation distances. To keep GM-inputs in the final product well below the 0.9% threshold defined by the EU, isolation distances of 20 m for silage and 50 m for grain maize, respectively, are proposed. An evaluation using statistical data on maize acreage and an aerial photographs assessment of a typical agricultural landscape by means of Geographic Information Systems (GIS) showed that spatial resources would allow applying the defined isolation distances for the cultivation of GM maize in the majority of the cases under actual Swiss agricultural conditions. The here developed approach, using defined criteria to consider the agricultural context of maize cultivation, may be of assistance for the analysis of cross-fertilization data in other countries.

Ecological impacts of genetically modified crops: ten years of field research and commercial cultivation.

The worldwide commercial cultivation of genetically modified (GM) crops has raised concerns about potential adverse effects on the environment resulting from the use of these crops. Consequently, the risks of GM crops for the environment, and especially for biodiversity, have been extensively assessed before and during their commercial cultivation. Substantial scientific data on the environmental effects of the currently commercialized GM crops are available today. We have reviewed this scientific knowledge derived from the past 10 years of worldwide experimental field research and commercial cultivation. The review focuses on the currently commercially available GM crops that could be relevant for agriculture in Western and Central Europe (i.e., maize, oilseed rape, and soybean), and on the two main GM traits that are currently commercialized, herbicide tolerance (HT) and insect resistance (IR). The sources of information included peer-reviewed scientific journals, scientific books, reports from regions with extensive GM crop cultivation, as well as reports from international governmental organizations. The data available so far provide no scientific evidence that the cultivation of the presently commercialized GM crops has caused environmental harm. Nevertheless, a number of issues related to the interpretation of scientific data on effects of GM crops on the environment are debated controversially. The present review highlights these scientific debates and discusses the effects of GM crop cultivation on the environment considering the impacts caused by cultivation practices of modern agricultural systems.

A conceptual framework for the design of environmental post-market monitoring of genetically modified plants.

Genetically modified plants (GMPs) may soon be cultivated commercially in several member countries of the European Union (EU). According to EU Directive 2001/18/EC, post-market monitoring (PMM) for commercial GMP cultivation must be implemented, in order to detect and prevent adverse effects on human health and the environment. However, no general PMM strategies for GMP cultivation have been established so far. We present a conceptual framework for the design of environmental PMM for GMP cultivation based on current EU legislation and common risk analysis procedures. We have established a comprehensive structure of the GMP approval process, consisting of pre-market risk assessment (PMRA) as well as PMM. Both programs can be distinguished conceptually due to principles inherent to risk analysis procedures. The design of PMM programs should take into account the knowledge gained during approval for commercialization of a specific GMP and the decisions made in the environmental risk assessments (ERAs). PMM is composed of case-specific monitoring (CSM) and general surveillance. CSM focuses on anticipated effects of a specific GMP. Selection of case-specific indicators for detection of ecological exposure and effects, as well as definition of effect sizes, are important for CSM. General surveillance is designed to detect unanticipated effects on general safeguard subjects, such as natural resources, which must not be adversely affected by human activities like GMP cultivation. We have identified clear conceptual differences between CSM and general surveillance, and propose to adopt separate frameworks when developing either of the two programs. Common to both programs is the need to put a value on possible ecological effects of GMP cultivation. The structure of PMM presented here will be of assistance to industry, researchers, and regulators, when assessing GMPs during commercialization.