Experiences and lessons learnt in the preparation of lists of occupational diseases and of the related diagnostic criteria

According to ILO, an occupational disease is \u201cAny disease contracted as a result of an exposure to risk factors arising from work activity\u201d. In most countries, a disease is defined \u201coccupational\u201d when the national authorities acknowledge its occupational origin. The main tool available to national authorities to recognize the occupational origin of a disease are the lists, but aims, contents, structure and size of the lists significantly vary, from countries which have not any list to countries having lists composed of more than hundred groups of occupational diseases, therefore harmonization is needed. A disease can be included in a list when the evidence of its link with exposure is strong, and solid diagnostic criteria exist. The main points for definition of diagnostic criteria are clinical features, occupational history and exposure, natural history and progress of the disease, and differential diagnosis. Other parameters are the minimum intensity of the exposure necessary to cause the disease and its minimum duration, the maximum latent period, that is the maximum time that can elapse from the induction or, as surrogate, from the beginning of exposure to the onset of the disease. Finally, the criteria of a minimum induction and the maximum disease-free period (from the end of the exposure to the onset of the disease) should be fulfilled. Unfortunately, these criteria cannot be guaranteed in condition mainly \u201csymptom based\u201d, such as low back pain, migraine, burnout, Karoshi. Also new diseases, diseases emerging from new risks or from new presentations of know risks deserve attention. Finally, the main properties of \u201cgood\u201d lists and criteria are credibility (involvement of experts and availability of references), consensus (among experts, employers, employees and governments), and consistency. These criteria and needs have been considered in the preparation of the document \u201cInternational Guidance Notes on the Diagnostic Criteria of Occupational Diseases\u201d

Development of new tools for bringing pesticide risk assessment in the small size enterprises and in the developing world

The role of pesticides in the modern society has been strengthened by the need for higher yield in food production and the ongoing battle against vector borne diseases in public health. Nevertheless, the toxicity of these chemicals is not fully specific to target organisms, thus posing a potential health threat to humans. In this frame, risk assessment and management are fundamental. In the occupational settings, variability of meteorological conditions, use of different concentrations of highboy variable mixtures, and significant variations in the application times and modalities make this task very complicated, underlining the need for novel approaches for conducting \u2018in field\u2019 preventive activities. New developments in pesticide risk assessment should start from the fact that the amount of information collected during the process of authorisation of new active ingredients is unique, similar to that available for pharmaceutical products, and that this significant amount of information is scarcely used in the post market risk assessment activities. In this light, a possible way forward for pesticide risk assessment is represented by a better exploitation of these data, in approaches with variable levels of complexity; the simplest, is the evaluation of the adherence of the use scenario under evaluation with the one checked and approved in the authorisation process and synthesised in the good agricultural practices. Other parameters such as Acceptable Operator Exposure Level (AOEL), acute reference dose (ArD) as well data regarding skin absorption, metabolism and relevant metabolites in animals can find use in the realisation of models adequate to estimate the dose and the risk without doing analysis, as well as to calculate provisional biological exposure indices, defining the dose supposed to be excreted in a subject exposed at the AOEL level. This can be done conducing real-life field studies to usable refine and validate the risk hypotheses generated through modelling

Establishing health-based biological exposure limits for pesticides : A proof of principle study using mancozeb

Pesticides represent an economical, labor-saving, and efficient tool for pest management, but their intrinsic toxic properties may endanger workers and the general population. Risk assessment is necessary, and biological monitoring represents a potentially valuable tool. Several international agencies propose biological exposure indices (BEI), especially for substances which are commonly absorbed through the skin. Biological monitoring for pesticide exposure and risk assessment seems a natural choice, but biological exposure limits (BEL) for pesticides are lacking. This study aims at establishing equivalent biological exposure limits (EBEL) for pesticides using real-life field data and the Acceptable Operator Exposure Level (AOEL) of mancozeb as the reference. This study included a group of 16 vineyard pesticide applicators from Northern Italy, a subgroup of a more extensive study of 28 applicators. Their exposure was estimated using \u201cpatch\u201d and \u201chand-wash\u201d methodologies, together with biological monitoring of free ethylene-bis-thiourea (ETU) excretion in 24-h pre- and post-exposure urine samples. Modeling was done using univariate linear regression with ETU excretion as the dependent variable and the estimated absorbed dose as the independent variable. The median skin deposition of mancozeb in our study population was 125 \u3bcg, leading to a median absorbed dose of 0.9 \u3bcg/kg. The median post-exposure ETU excretion was 3.7 \u3bcg. The modeled EBEL for mancozeb was 148 \u3bcg of free ETU or 697 \u3bcg of total ETU, accounting for around 75% of the maximum theoretical excretion based on a mass balance model. Although preliminary and based on a small population of low-exposed workers, our results demonstrate a procedure to develop strongly needed biological exposure limits for pesticides

Trends in occupational diseases in the Italian agricultural sector, 2004-2017

Objective: To estimate the incidence of, trends in and effect of change in reporting rules on occupational diseases (ODs) in the Italian agricultural sector. Methods: Over a 14-year period (2004-2017), ODs among Italian agricultural workers were diagnosed by physicians and reported to the National Institute for Insurance against Workplace Accidents and Occupational Diseases. OD was defined as a disease with a specific clinical diagnosis (International Classification of Diseases) and was predominantly caused by work-related factors. Trends in incidence and effects of changed eligibility criteria for reporting occupational musculoskeletal disorders (MSDs) and noise-induced hearing loss (NIHL) were estimated using a Poisson regression model. Results: In 2017, the incidence of all ODs was 1295 per 100 000 agricultural workers. MSDs (961 per 100 000 workers) were the most frequently occurring ODs. MSDs and NIHL showed statistically significant increasing time trends, 26% and 7% annual increase, respectively, during the 2004-2017 period. There was no statistically significant change in the incidence of occupational respiratory, skin and cancer diseases during the 14-year period. After changes in reporting rules, the incidence of MSDs showed an immediate increased effect, with an incidence rate ratio (IRR) of 2.9 (95% CI 2.65 to 3.14) and a significant annual decreasing trend of -9% (95% CI -6% to -12%) over the years after the changed reporting rules (from 2008 to 2017), and an immediate effect on NIHL with an IRR of 1.3 (95% CI 1.13 to 1.53). Conclusion: In total, 1.3% of the Italian agricultural workers were diagnosed in 2017 as having an OD. Over a 14-year period, the annual incidence of ODs showed a considerable increasing trend consistent with changed eligibility reporting criteria for occupational MSDs and to a lesser extent for NIHL

Valutazione dei dati sperimentali per la neurotossicit\ue0 dello sviluppo dei pesticidi

EVALUATION OF EXPERIMENTAL DATA FOR DEVELOPMENTAL NEUROTOXICITY OF PESTICIDES. Epidemiological studies on neurodevelopmental effects of pesticides are inconclusive. Experimental developmental neurotoxicity studies, sometimes show effects on pups given doses lower than adults; most of the times these effects were transient, aspecific, with scattered biochemical, molecular or neurobehavioural changes, generally associated with high bolus doses. At repeated low doses, effects in pups did not occur at doses lower than in adults.Since the effects of high bolus doses are possible, preventive interventions should aim at reducing these exposures

La durata dell’esposizione: informazione negletta nella valutazione del rischio da pesticidi

Introduzione In ambito di valutazione preliminare all\u2019autorizzazione all\u2019impiego, ma anche in studi sul campo, la valutazione del rischio da antiparassitari \ue8 condotta ipotizzando che la durata di una giornata lavorativa sia pari a 8 ore. Purtroppo, in agricoltura, la giornata lavorativa non ha praticamente mai una durata standard, e nella raccolta di dati condotta in corso di studi sul campo, con stima dell\u2019assorbimento cutaneo, non si tiene conto del fatto che i lavoratori lavano le mani pi\uf9 volte durante la giornata lavorativa. In questi casi, considerare la durata di esposizione del corpo e delle mani 8 ore senza considerare eventuali lavaggi effettuati nel corso della giornata potrebbe portare un errore nella valutazione della dose assorbita e, quindi, del rischio per la salute. Obiettivi Lo scopo di questo studio era di stimare la dose di antiparassitario assorbita in corso di applicazioni in agricoltura e quantificare l'influenza della durata dell'esposizione sulla dose interna usando una nuova tecnica statistica. Metodi In una serie di studi sul campo su 29 lavoratori che avevano applicato il fungicida etilenbisditiocarbammato di manganese e zinco (mancozeb) su vigneti per 38 giorni lavorativi, sono stati raccolti tre set di dati: informazioni dettagliate sulle attivit\ue0 lavorative svolte per ogni giornata lavorativa, dose cutanea \u201cpotenziale\u201d (al disopra dell\u2019abbigliamento) e effettiva (sulla cute) attraverso l\u2019applicazione di pads cutanei. \uc8 stata inoltre determinata la concentrazione del principale metabolita del mancozeb, etilentiourea (ETU) sia nella 24 ore precedenti l\u2019esposizione sia nelle 24 successive, La valutazione statistica \ue8 stata condotta utilizzando il linguaggio e l'ambiente per il calcolo statistico \u201cR\u201d. Risultati L\u2019aver considerato nei nostri calcoli la durata dell\u2019esposizione ha portato a una riduzione significativa e quindi a stime pi\uf9 realistiche della dose assorbita rispetto aalle stime condotte ipotizzando una giornata lavorativa standard. In particolare, la dose totale assorbita (escluse le mani), la dose assorbita attraverso le mani, e la dose totale sono risultate pari a meno di 1 ng/kg pc, 3 ng/kg pc e 3 ng/kg pc rispettivamente considerando un turno di 8 ore. La correzione per tempo reale del turno e lavaggio delle mani ha portato ad una riduzione, rispettivamente, del 50%, 81% e 80%. Dopo tale elaborazione, la dose totale assorbita correlava meglio con i livelli di ETU delle urine delle 24 ore post-esposizione rispetto alla dose delle mani, sebbene pi\uf9 del 90% della dose totale assorbita stimata provenga dalle mani. Conclusioni Una migliore capacit\ue0 di stimare la dose totale di antiparassitari assorbita, unitamente alla identificazione di indicatori biologici di dose affidati e validati, come nel nostro caso l'ETU urinaria, possono facilitare la modellizzazione dei livelli di esposizione e permettere di mettere a punto strumenti per la valutazione del rischio senza necessit\ue0 di ricorrere a misure (\u201cprofili\u201d), o anche promuovere l'uso del monitoraggio biologico nella valutazione del rischio da antiparassitari in un ambito critico come l\u2019agricoltura

Urinary ethylenethiourea as biomarkers of exposure to ethylenebisdithiocarbamates in floriculture workers in Ecuador

Floriculture represents one of the major sources of income in Ecuador that is one of the greatest worldwide producers of ornamental flowers. Floriculture can be carried out both in open fields and in greenhouses with an extensive use of pesticides, among which, ethylenbisdithiocarbamate fungicides (EBDTCs). Aim of this study was to assess EBDTCs exposure in Ecuadorian floricultural workers by the determination of the urinary excretion of the major metabolite of these compounds, ethylenethiourea (ETU). Thirty-six floriculture workers and 34 unexposed healthy subjects (controls) from an Andean region entered the study. Workers were exposed to EBDTCs while applying plant protection products, and during re-entry activities or crop maintenance in one open field and two greenhouse farms. They provided morning pre-exposure (n=31) and afternoon post-exposure (n=24) urine spot samples. Controls provided one urine spot sample collected in the morning. In agricultural workers median ETU in pre- and after-exposure samples was 3.2 (<0.5-34.5) and 6.2 (1.5-26.5) \ub5g/g creatinine. Although ETU increased after the workshift the difference was not significant. ETU was higher in workers then in controls (0.7, <0.5-7.1 \ub5g/g creatinine, p < 0.01). When subjects were divided according to job titles, applicators showed the highest ETU (17.0, 1.5-34.5 \ub5g/g creatinine) whereas growing, post-harvesting and maintenance workers showed similar levels (4.3, <0.5-26.5; 2.8, <0.5-11.1; 4.8, 3.2-6.5 \ub5g/g creatinine, respectively). Higher ETU was observed in greenhouse compared to open field workers (p < 0.01). This study suggests that Ecuadorian floricultures are exposed to EBDTCs at levels approaching those observed in Italian vineyard workers. The lack of difference between ETU in pre- vs. post-exposure samples is attributable to previous day exposure, in fact the kinetic of excretion is such that in prior to next shift urine significant amount of ETU is still present

Methods for the Identification of Outliers and Their Influence on Exposure Assessment in Agricultural Pesticide Applicators : a Proposed Approach and Validation Using Biological Monitoring

The "patch" approach for skin exposure assessment can easily be combined with biological monitoring in real-life pesticide studies. Nevertheless, this approach is sensitive to outliers, with values markedly deviating from other members of the sample, which can result in a gross overestimation of exposure. This study aimed at developing methods for outlier identification and validating them while using biological monitoring. Twenty-seven workers applying mancozeb in Italian vineyards participated in this study. Their skin exposure was estimated while using the patch methodology, while ethylene-thiourea (ETU) was measured in the 24-h post-exposure urine as a biomarker of exposure. The outliers were detected using methods that were based on the multiplication of the median, the median absolute deviation, and boxplots. The detection rate varied between 2.3% and 17.3%. The estimated median skin exposure of 3.2 \u3bcg was reduced to 1.2 \u3bcg when the modified Z score was used. The highest reduction in the skin exposure was above 54 \u3bcg. The use of the modified Z score for outlier detection resulted in an increase in the correlation coefficient between the skin exposure and the urine ETU levels from 0.46 to 0.71, which suggested the validity of the approach. Future studies should standardize and improve the methods for pesticide exposure and risk assessment