Stefan Mandic-Rajcevic

Biological monitoring of exposure to tebuconazole in winegrowers

Tebuconazole (TEB) is a fungicide widely used in vineyards and is a suspected teratogen for humans. The aim of this research was to identify urinary biomarkers and the best sampling time for the biological monitoring of exposure to TEB in agricultural workers. Seven vineyard workers of the Monferrato region, Piedemont, Italy, were investigated for a total of 12 workdays. They treated the vineyards with TEB for 1–2 consecutive days, one of them for 3 days. During each application coveralls, underwears, hand washing liquids and head coverings were used to estimate dermal exposure. For biomonitoring, spot samples of urine from each individual were collected starting from 24 h before the first application, continuing during the application, and again after the application for about 48 h. TEB and its metabolites TEB-OH and TEB-COOH were measured by liquid chromatography/triple quadrupole mass spectrometry. TEB contamination of coveralls and total dermal exposure showed median levels of 6180 and 1020 μg. Urinary TEB-OH was the most abundant metabolite; its excretion rate peaked within 24 h after product application (post 24 h). In this time frame, median levels of TEB-OH and TEB-COOH ranged from 8.0 to 387.8 μg/l and from 5.7 to 102.9 μg/l, respectively, with a ratio between the two metabolites of about 3.5. The total amount of urinary metabolites (U-TEBeq) post 24 h was significantly correlated with both TEB on coveralls and total dermal exposure (Pearson’s r=0.756 and 0.577). The amount of metabolites excreted in urine represented about 17% of total dermal TEB exposure. Our results suggest that TEB-OH and TEB-COOH in post-exposure urine samples are promising candidates for biomonitoring TEB exposure in agricultural workers.

Testing a cumulative and aggregate exposure model using biomonitoring studies and dietary records for Italian vineyard spray operators

The need for improved tools to estimate the cumulative and aggregate exposure to compounds such as plant protection products (PPPs) is recognised in the EU Regulation 1107/2009. A new model has been developed to estimate the exposure within a population to single compounds or compounds within a Cumulative Action Group, considering dietary and non-dietary sources and multiple exposure routes. To test the model a field study was carried out in Italy with operators applying tebuconazole fungicides, with measurements of dermal exposure collected. Whole urine samples were collected and analysed to provide values for the absorbed dose of tebuconazole, with duplicate diet samples collected and analysed as a measure of dietary exposures. The model provided predicted values of exposure for combined dietary and non-dietary routes of exposures which were compared to the measured absorbed dose values based on urinary analysis. The model outputs provided mean daily exposure values of 1.77 (± 1.96) µg a.s./kg BW which are comparable to measured mean values from the biomonitoring field study of 1.73 (± 1.31) µg a.s./kg BW. To supplement the limited measurement data available, comparisons against other models were also made and found to be comparable.

Exposure to priority organochlorine contaminants in the Italian general population. Part 2. : fifteen priority polychlorinated biphenyl congeners in blood serum

Concentrations of 36 polychlorinated biphenyl (PCB) congeners were measured in serum of 372 Italian residents of general population living in Novafeltria, Pavia, and Milan. Total PCB level differed significantly between these sites (p < 0.0001) with median concentrations of 836.50, 1354.57, and 2062.08 pmol/g lipid, respectively. However, there is no evidence for the difference in distribution of total PCB levels by genders. Total dioxin-like PCBs differed significantly (p < 0.0001) between the sites (median 109.78, 50.88, and 166.99 pmol/g lipid, respectively) and genders of Novafeltria and Pavia (p = 0.011 and 0.009, respectively). PCB 138, 153, 170, and 180 differed significantly between the places of residence (p < 0.0001) with higher values in Milan population. In the overall population, total PCB and PCB 138, 153, 156, 170, and 180 correlated positively with age (correlations range between 0.320 and 0.569, p < 0.0001). In Novafeltria, the correlations ranged between 0.545 and 0.670, and in Pavia, the correlations ranged between 0.516 and 0.666. In Milan, correlations with age range between 0.327 and 0.417 for total PCB and congeners 138, 153, and 180. With an exception of PCB 170, there was no evidence of significant difference in the distribution of most abundant PCB congeners and total PCB across the body mass index categories.

WHO/ILO work-related burden of disease and injury: Protocol for systematic reviews of occupational exposure to dusts and/or fibres and of the effect of occupational exposure to dusts and/or fibres on pneumoconiosis

BACKGROUND The World Health Organization (WHO) and the International Labour Organization (ILO) are developing a joint methodology for estimating the national and global work-related burden of disease and injury (WHO/ILO joint methodology), with contributions from a large network of experts. In this paper, we present the protocol for two systematic reviews of parameters for estimating the number of deaths and disability-adjusted life years attributable to pneumoconiosis from occupational exposure to dusts and/or fibres, to inform the development of the WHO/ILO joint methodology. OBJECTIVES We aim to systematically review studies on occupational exposure to dusts and/or fibres (Systematic Review 1) and systematically review and meta-analyse estimates of the effect of occupational exposure to dusts and/or fibres on pneumoconiosis (Systematic Review 2), applying the Navigation Guide systematic review methodology as an organizing framework. DATA SOURCES Separately for Systematic Reviews 1 and 2, we will search electronic academic databases for potentially relevant records from published and unpublished studies, including Medline, EMBASE, Web of Science and CISDOC. We will also search electronic grey literature databases, Internet search engines and organizational websites; hand-search reference list of previous systematic reviews and included study records; and consult additional experts. STUDY ELIGIBILITY AND CRITERIA We will include working-age (≥15 years) study participants in the formal and informal economy in any WHO and/or ILO Member State but exclude children (<15 years) and unpaid domestic workers. Eligible risk factors will be dusts and/or fibres from: (i) asbestos; (ii) silica; and/or (iii) coal (defined as pure coal dust and/or dust from coal mining). Included outcomes will be (i) asbestosis; (ii) silicosis; (iii) coal worker pneumoconiosis; and (iv) unspecified pneumoconiosis. For Systematic Review 1, we will include quantitative prevalence studies of occupational exposure to dusts and/or fibres (i.e. no versus any exposure) stratified by country, sex, age and industrial sector or occupation. For Systematic Review 2, we will include randomized controlled trials, cohort studies, case-control studies and other non-randomized intervention studies with an estimate of any occupational exposure to dusts and/or fibres on the prevalence of, incidence of or mortality due to pneumoconiosis, compared with the theoretical minimum risk exposure level of no exposure. STUDY APPRAISAL AND SYNTHESIS METHODS At least two review authors will independently screen titles and abstracts against the eligibility criteria at a first stage and full texts of potentially eligible records at a second stage, followed by extraction of data from qualifying studies. At least two review authors will assess risk of bias and the quality of evidence, using the most suited tools currently available. For Systematic Review 2, if feasible, we will combine relative risks using meta-analysis. We will report results using the guidelines for accurate and transparent health estimates reporting (GATHER) for Systematic Review 1 and the preferred reporting items for systematic reviews and meta-analyses guidelines (PRISMA) for Systematic Review 2. PROSPERO REGISTRATION NUMBER CRD42018084131.

Principles and Application of the Integrated Pest Management Approach. Biological Pesticides

Protection of crops from pests and from ravenous animals was long accomplished with the use of ‘natural’ means, before the introduction of ‘modern’ synthetic chemicals as pesticides in the twentieth century. The widespread use of synthetic organic chemicals as pesticides in the last several decades has contributed to the ‘background’ contamination of all environmental and biological compartments with trace amounts of small organic compounds, the combined effect of which on the health of humans and on the general well-being of complex ecological systems is far from being understood. In particular, it is claimed that the presence of trace amounts of such compounds in human food may contribute to impair the health of sensitive individuals, especially in the developmental and early-age stages of life, although there is not a clear-cut consensus on this problem. The request from consumers, mainly in developed Western countries, of food produced under perceived healthier conditions than those of mass-production, has prompted a backslash of interest in traditional, lower-yield techniques such as ‘organic farming’ and thus the necessity to protect consumers from unsubstantiated claims of food quality through the issuing of voluntary codes by producers and of guidelines such as Codex Alimentarius at the level of international Organizations. Another driving force into a renaissance of ‘traditional’ farming techniques is understanding that they can be successfully merged to ‘modern’ ones to achieve better productions with lower environmental impact, lower consumption of selective but expensive Plant Protection Products, lower contamination of food with residues. Another trigger to seek alternatives to the conventional means of pest fighting is acknowledgement that later generations may develop resistance to current pesticides in a continuous ‘chemical war’ between human scientific intellect and natural evolution of organisms. Traditional agricultural wisdom long recognized the power of coenobioses and used co-cultivation of different crops as a means to deter parasites by exploiting the natural emission of insect repellents and mutual fight between natural hosts of crops and invading organisms. Of course, since even ‘natural’ substances long employed to fight parasites of plants and food are intrinsically toxic not only to target species but also to several others, including the human, risk assessment of their use is mandatory to fully benefit of their strength without unnecessary risk for producers, consumers and the global environment. The recent exploitation of natural as well as of engineered organisms and of their toxic products as pesticides is another means the reach and limitations of which need to be fully understood. Examples of how these seemingly conflicting requirements have been or can be harmonized will be presented and discussed.

Assessment of penconazole exposure in winegrowers using urinary biomarkers

&NA; Penconazole (PEN) is a fungicide used in agriculture. The aim of this work was to evaluate the exposure to PEN in vineyard workers focusing on urinary biomarkers. Twenty‐two agricultural workers were involved in the study; they were investigated during PEN applications and re‐entry work, performed for 1–4 consecutive working days, for a total of 42 mixing and applications and 12 re‐entries. Potential and actual dermal exposure, including hand exposure, were measured using pads and hand washes. Urine samples were collected starting before the first application, continuing during the work shift, and ending 48 h after the last shift. The determination of PEN in dermal samples and PEN metabolites in urine was performed by liquid chromatography tandem mass spectrometry. Dermal potential body exposure and actual total exposure showed median levels ranging from 18 to 3356 &mgr;g and from 21 to 111 &mgr;g, respectively. Urinary monohydroxyl‐derivative PEN‐OH was the most abundant metabolite; its excretion rate peaked within 24 h after the work shift. In this period, median concentrations of PEN‐OH and the carboxyl‐derivative PEN‐COOH ranged from 15.6 to 27.6 &mgr;g/L and from 2.5 to 10.2 &mgr;g/L, respectively. The concentration of PEN‐OH during the work shift, in the 24 h after and in the 25–48 h after the work shift were correlated with actual body and total dermal exposure (Pearsons r from 0.279 to 0.562). Our results suggest that PEN‐OH in the 24 h post‐exposure urine is a promising candidate for biomonitoring PEN exposure in agricultural workers.

Comparing the Strain Index and the Revised Strain Index Application in the Dairy Sector

Repeated forceful efforts, high muscular loads in the wrist flexor and extensor muscles and awkward hand positions during milking can contribute to wrist and hand diseases. Thus, evaluating the risk of biomechanical overload of milking parlor workers’ wrist with an accurate method is fundamental. Aims of the study were: (1) evaluating the wrist’s biomechanical overload in the milking routine subtasks: pre-dipping, wiping/stripping, attacking, post-dipping; (2) comparing the results obtained from Strain Index and Revised Strain Index methods application; (3) evaluating the quality of the approach, the concordance and the possible difficulties in applying and interpreting the two evaluation methods.

Environmental and biological monitoring for the identification of main exposure determinants in vineyard mancozeb applicators

Grapevine is a vulnerable crop to several fungal diseases often requiring the use of ethylenebisdithiocarbamate (EBDC) fungicides, such as mancozeb. This fungicide has been reported to have goitrogenic, endocrine disrupting, and possibly immunotoxic effects. The aim of this study was to assess workers’ exposure in two scenarios of mancozeb application and analyse the main determinants of exposure in order to better understand their mechanism of influence. Environmental monitoring was performed using a modified Organisation for Economic Co-operation and Development (OECD) “patch” methodology and by hand-wash collection, while mancozeb’s metabolite, ethylenethiourea (ETU), was measured in 24-h preexposure and postexposure urine samples. Liquid chromatography–mass spectrometry was used for determination of mancozeb and ETU in different kinds of samples. Closed tractor use resulted in 40 times lower potential exposure compared with open tractor. Coveralls reduced skin exposure 4 and 10 times in case of open and closed tractors, respectively. Gloves used during application resulted in 10 times lower hand exposure in open but increased exposure in closed tractors. This study has demonstrated that exposure to mancozeb is low if safe occupational hygiene procedures are adopted. ETU is confirmed as suitable biological marker of occupational exposure to mancozeb, but the absence of biological exposure limits significantly reduces the possibility to interpret biological monitoring results in occupationally exposed workers.

Risk Quantification of Multigenic Conditions for SNP Array Based Direct-to-Consumer Genomic Services

Genome wide association studies (GWAS) are typically designed as case-control studies, collecting thousands of sick and healthy individuals, genotyping hundreds of thousands of SNPs, and documenting the SNPs which are more abundant in one group or the other. Direct-to-consumer genetic testing has opened the possibility for a regular person to receive data about his/her genotype, but the validity of risk assessment procedures and the final genetic risk estimate have been questioned. Many authors have discussed the advantage of use of the asymptotic Bayes factor (ABF) to measure the strength of SNP/trait associations, over the use of p-values. We propose a ABF based heuristic to filter-our and select SNP/trait associations to be used in multigenic risk assessment.