Pesticide drift mitigation measures appear to reduce contamination of non-agricultural areas, but hazards to humans and the environment remain.

Pesticide drift onto non-agricultural land is a common problem in intensively farmed regions, and national action plans have been established across Europe to prevent it. Here, we analyzed official data on pesticide residues in grass samples collected over six years to determine whether implemented measures to reduce pesticide drift were effective. We used 306 samples collected between 2014 and 2020 on non-agricultural land in one of the most intensively managed apple and wine growing regions in Europe, the Autonomous Province of Bolzano-South Tyrol, Italy. Samples were analyzed for up to 314 substances by gas chromatography and mass spectrometry. Percentage of sites with multiple pesticides and number of pesticides decreased between 2014 and 2020. Fungicides were most often detected, with fluazinam found on 74 % and captan on 60 % of the contaminated sites (53 sites out of a total of 88 sites were contaminated). The most frequently found insecticide, phosmet, was detected in 49 % of the contaminated sites. Only one herbicide, oxadiazon, was detected in <1 % of the sites; glyphosate was not analyzed. The percentage of residues with human hazard properties increased significantly across years regarding reproductive toxicity (from 21 % of the detected substances in 2014 to 88 % in 2020) and specific target organ toxicity (0 % in 2014 to 21 % in 2020). Percentages of substances associated with endocrine-disruption (89 % of substances across years) or carcinogenic properties (45 % of substances across years) remained constant. The percentage of sites where concentrations in grass samples exceeded the surrogate maximum residue levels (MRLs) for lettuce also remained constant. Potential ecotoxicological hazards of detected residues regarding acute contact toxicity to honeybees remained high over the study years, while the acute and chronic toxicity to earthworms decreased. Our results suggest that while drift mitigation measures contributed some reduction in pesticide contamination, they were not sufficient to eliminate substantial risks to human health and the environment in nontarget areas.

Response to: "letter to the editor regarding the article "the global distribution of acute unintentional pesticide poisoning: estimations based on a systematic review"" by Dunn et al. 2021 in BMC public health.

In a correspondence to BMC Public Health, Dunn et al. (Dunn SE, Reed J and Neumann C. BMC Public Health (n.d)) respond to our review on the occurrence of unintentional, acute pesticide poisoning (UAPP). Based on a systematic review and further data sources we estimated that about 385 million cases of UAPP occur annually world-wide including around 11,000 fatalities (Boedeker W. et al. BMC Public Health:1875, 2020).

The global distribution of acute unintentional pesticide poisoning: estimations based on a systematic review.

BACKGROUND: Human poisoning by pesticides has long been seen as a severe public health problem. As early as 1990, a task force of the World Health Organization (WHO) estimated that about one million unintentional pesticide poisonings occur annually, leading to approximately 20,000 deaths. Thirty years on there is no up-to-date picture of global pesticide poisoning despite an increase in global pesticide use. Our aim was to systematically review the prevalence of unintentional, acute pesticide poisoning (UAPP), and to estimate the annual global number of UAPP. METHODS: We carried out a systematic review of the scientific literature published between 2006 and 2018, supplemented by mortality data from WHO. We extracted data from 157 publications and the WHO cause-of-death database, then performed country-wise synopses, and arrived at annual numbers of national UAPP. World-wide UAPP was estimated based on national figures and population data for regions defined by the Food and Agriculture Organization (FAO). RESULTS: In total 141 countries were covered, including 58 by the 157 articles and an additional 83 by data from the WHO Mortality Database. Approximately 740,000 annual cases of UAPP were reported by the extracted publications resulting from 7446 fatalities and 733,921 non-fatal cases. On this basis, we estimate that about 385 million cases of UAPP occur annually world-wide including around 11,000 fatalities. Based on a worldwide farming population of approximately 860 million this means that about 44% of farmers are poisoned by pesticides every year. The greatest estimated number of UAPP cases is in southern Asia, followed by south-eastern Asia and east Africa with regards to non-fatal UAPP. CONCLUSIONS: Our study updates outdated figures on world-wide UAPP. Along with other estimates, robust evidence is presented that acute pesticide poisoning is an ongoing major global public health challenge. There is a need to recognize the high burden of non-fatal UAPP, particularly on farmers and farmworkers, and that the current focus solely on fatalities hampers international efforts in risk assessment and prevention of poisoning. Implementation of the international recommendations to phase out highly hazardous pesticides by the FAO Council could significantly reduce the burden of UAPP.

Pesticides and public health: an analysis of the regulatory approach to assessing the carcinogenicity of glyphosate in the European Union.

The present paper scrutinises the European authorities' assessment of the carcinogenic hazard posed by glyphosate based on Regulation (EC) 1272/2008. We use the authorities' own criteria as a benchmark to analyse their weight of evidence (WoE) approach. Therefore, our analysis goes beyond the comparison of the assessments made by the European Food Safety Authority and the International Agency for Research on Cancer published by others. We show that not classifying glyphosate as a carcinogen by the European authorities, including the European Chemicals Agency, appears to be not consistent with, and in some instances, a direct violation of the applicable guidance and guideline documents. In particular, we criticise an arbitrary attenuation by the authorities of the power of statistical analyses; their disregard of existing dose-response relationships; their unjustified claim that the doses used in the mouse carcinogenicity studies were too high and their contention that the carcinogenic effects were not reproducible by focusing on quantitative and neglecting qualitative reproducibility. Further aspects incorrectly used were historical control data, multisite responses and progression of lesions to malignancy. Contrary to the authorities' evaluations, proper application of statistical methods and WoE criteria inevitably leads to the conclusion that glyphosate is 'probably carcinogenic' (corresponding to category 1B in the European Union).

Critical evaluation of the use of dogs in biomedical research and testing in Europe.

Dogs are sometimes referred to as "man's best friend" and with the increase in urbanization and lifestyle changes, dogs are seen by their owners as family members. Society expresses specific concerns about the experimental use of dogs, as they are sometimes perceived to have a special status for humans. This may appear somewhat conflicting with the idea that the intrinsic value of all animals is the same, and that also several other animal species are used in biomedical research and toxicology. This aspect and many others are discussed in an introductory chapter dealing with ethical considerations on the use of dogs as laboratory animals. The report gives an overview on the use of dogs in biomedical research, safety assessment and the drug developmental process and reflects the discussion on the use of dogs as second (non-rodent)species in toxicity testing. Approximately 20,000 dogs are used in scientific procedures in Europe every year, and their distinct genetic, physiological and behavioral characteristics may support their use as models for e.g. behavioral analysis and genetic research. Advances in the 3Rs (Replacement, Reduction and Refinement of experiments using dogs) are described, potential opportunities are discussed and recommendations for further progress in this area are made.

The utility of the minipig as an animal model in regulatory toxicology.

In this article we review the value and utility of the minipig as an animal model in regulatory toxicity testing. Our review is based on detailed consideration of the comparative biology of the minipig, and of the practical features of toxicity testing in the minipig. The minipig presents a favourable profile as a non-rodent toxicology model, in terms of the similarity to man and also in terms of applicability to different study types. Studies of general toxicology can be performed in the minipig by oral, cutaneous, parenteral and inhalation routes. For reproductive toxicology studies the minipig offers numerous advantages as a non-rodent model although the lack of placental transfer of macromolecules may limit the role of the minipig in reproductive testing of biotechnology products. For safety pharmacology studies the minipig is an advantageous model, particularly as regards the cardiovascular system. The immune system of the pig is better characterized than that of the dog, making the pig an interesting alternative model to the nonhuman primate for therapeutic approaches based on manipulation of the immune system. Overall, this review leads us to believe that the minipig might be a better non-rodent toxicology model than the dog. At the present time, however, insufficient comparative data is available to permit a rigorous evaluation of the predictivity of the minipig for human drug-induced toxicities and research is urgently needed to provide experimental data for evaluation of the hypothesis that minipig studies may better reflect human drug-induced toxicities than studies performed in traditional non-rodent toxicology models. It would be of particular value to gain a better vision of the potential utility of the minipig as a model for the safety testing of new biologics, where the minipig could potentially replace the use of non-human primates in the testing of some new products.