Statistical Analysis of Avian Reproduction Studies

Avian reproduction studies for regulatory risk assessment are undergoing review by regulatory authorities, often leading to requests for statistical re-analysis of older studies using newer methods, sometimes with older study data that do not support these newer methods. We propose detailed statistical protocols with updated statistical methodology for use with both new and older studies and recommend improvements in experimental study design to set-up future studies for robust statistical analyses. There is increased regulatory and industry attention to the potential use of benchmark dose (BMD) methodology to derive the point of departure in avian reproduction studies, to be used as the endpoint in regulatory risk assessment. We present benefits and limitations of this BMD approach for older studies being re-evaluated and for new studies designed for with BMD analysis anticipated. Model averaging is recommended as preferable to model selection for BMD analysis. Even for a new study following the modified experimental design analyses with BMD methodology will only be possible for a restricted set of response variables. The judicious use of historical control data, identification of outlier data points, increased use of distributions more consistent with the nature of the data collected as opposed to forcing normality-based methods, and trend-based hypothesis tests are shown to be effective for many studies, but limitations on their applicability are also recognized and explained. Updated statistical methodologies are illustrated with case studies conducted under existing regulatory guidelines that have been submitted for product registrations. Through the adoption of improved avian reproduction study design elements combined with the suggested revised statistical methodologies the conduct, analyses, and utility of avian reproduction studies for avian risk assessments can be improved.

“Good Epidemiology Practice” Guidelines for Pesticide Exposure Assessment

Both toxicology and epidemiology are used to inform hazard and risk assessment in regulatory settings, particularly for pesticides. While toxicology studies involve controlled, quantifiable exposures that are often administered according to standardized protocols, estimating exposure in observational epidemiology studies is challenging, and there is no established guidance for doing so. However, there are several frameworks for evaluating the quality of published epidemiology studies. We previously developed a preliminary list of methodology and reporting standards for epidemiology studies, called Good Epidemiology Practice (GEP) guidelines, based on a critical review of standardized toxicology protocols and available frameworks for evaluating epidemiology study quality. We determined that exposure characterization is one of the most critical areas for which standards are needed. Here, we propose GEP guidelines for pesticide exposure assessment based on the source of exposure data (i.e., biomonitoring and environmental samples, questionnaire/interview/expert record review, and dietary exposures based on measurements of residues in food and food consumption). It is expected that these GEP guidelines will facilitate the conduct of higher-quality epidemiology studies that can be used as a basis for more scientifically sound regulatory risk assessment and policy making.

Relevance of body weight effects for the population development of common voles and its significance in regulatory risk assessment of pesticides in the European Union

Background The common vole (Microtus arvalis) is typically the wild mammal species driving regulatory pesticide risk assessment (RA) in Europe. The risk assessment endpoint for wild mammals is taken from the studies conducted mainly with rodents for the toxicological part of the dossier. Body weight effects in these studies are often driving the selection of the No Observed Adverse Effect Level (NOAEL) used for wildlife risk assessment. Thus, assessing body weight effects in voles very frequently constitutes a key scenario in the RA. Although many studies on ecology, reproductive biology, population genetics, and other aspects of common voles are available, the relevance of body weight for their survival and reproduction has not yet been specifically analysed. There is also little guidance on how to quantitatively deal with body weight effects in the regulatory risk assessment of pesticides. Results We evaluated the population relevance of body weight effects on voles by analysis of a dataset from a multi-annual study with repeated life-trapping and genotyping, and have correlated body weight with reproductive success, taking account of the seasonality of body weight. Body weight and growth were similar between reproducing and non-reproducing females. The number of confirmed offspring indicated no correlation with parental body weight. Reproductive success of the voles was mainly influenced by the date of birth, i.e., animals born in spring have a higher chance to reproduce. Body weight did not correlate with life span during most of the year, except for autumn. Animals weighing < 15 g in October did not survive winter. Conclusions These results demonstrate no detectable influence of common vole body weight on reproductive success and survival during most times of the year. The results of this study suggest that, additional to the hazard information from toxicity studies, ecological information on voles as a typical species of concern should be considered in the regulatory risk assessment of pesticides.

Wild Bee Toxicity Data for Pesticide Risk Assessments

Pollination services are vital for agriculture, food security and biodiversity. Although many insect species provide pollination services, honeybees are thought to be the major provider of this service to agriculture. However, the importance of wild bees in this respect should not be overlooked. Whilst regulatory risk assessment processes have, for a long time, included that for pollinators, using honeybees (Apis mellifera) as a protective surrogate, there are concerns that this approach may not be sufficiently adequate particularly because of global declines in pollinating insects. Consequently, risk assessments are now being expanded to include wild bee species such as bumblebees (Bombus spp.) and solitary bees (Osmia spp.). However, toxicity data for these species is scarce and are absent from the main pesticide reference resources. The aim of the study described here was to collate data relating to the acute toxicity of pesticides to wild bee species (both topical and dietary exposure) from published regulatory documents and peer reviewed literature, and to incorporate this into one of the main online resources for pesticide risk assessment data: The Pesticide Properties Database, thus ensuring that the data is maintained and continuously kept up to date. The outcome of this study is a dataset collated from 316 regulatory and peer reviewed articles that contains 178 records covering 120 different pesticides and their variants which includes 142 records for bumblebees and a further 115 records for other wild bee species.