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Assessment of exposure of professional agricultural operators to pesticides

Wong HL, Garthwaite DG, Ramwell CT, Brown CD

Sci Total Environ, 2018 Apr 01;619-620:874-882.
PMID: 29734633 DOI: 10.1016/j.scitotenv.2017.11.127

This study investigates how field practices in handling and applying pesticides influence the long-term patterns of professional agricultural operators' exposure to pesticides. It presents the first use of a comprehensive pesticide application dataset collected on behalf of the European Food Safety Authority with 50 operators selected to cover arable and orchard cropping systems in Greece, Lithuania and the UK. Exposure was predicted based on the harmonised Agricultural Operator Exposure Model (AOEM) and compared with Acceptable Operator Exposure Levels (AOELs). The amount of pesticides handled by individual operators across a cropping season was largest in the UK arable and orchard systems (median 580 and 437kg active substance, respectively), intermediate for the arable systems in Greece and Lithuania (151 and 77kg, respectively), and smallest in the Greek orchard system (22kg). Overall, 30 of the 50 operators made at least one application within a day with predicted exposure greater than the AOEL. The rate of AOEL exceedance was greatest in the Greek cropping systems (8 orchard operators, 2.8-16% of total applications; 7 arable operators, 1.1-14% of total applications), and least for the Lithuanian arable system (2 operators, 2.9-4.5% of total applications). Instances in Greece when predicted exposure exceed the AOEL were strongly influenced by the widespread use of wettable powder formulations (>40% of the total pesticide active substance handled for 11 of the 20 Greek operators). In contrast, the total area of land treated with an active substance on a single day was more important in the UK and Lithuania (95th percentile observed value was 132 and 19haday-1 for UK arable and orchard systems, respectively). Study findings can be used to evaluate current assumptions in regulatory exposure calculations and to identify situations with potential risk that require further analysis including measurements of exposure to validate model estimations.
Assessment of occupational exposure to pesticide mixtures with endocrine-disrupting activity

Wong HL, Garthwaite DG, Ramwell CT, Brown CD

Environ Sci Pollut Res Int, 2019 Jan;26(2):1642-1653.
PMID: 30448946 DOI: 10.1007/s11356-018-3676-5

Occupational exposure to pesticide mixtures comprising active substance(s) and/or co-formulant(s) with known/possible endocrine-disrupting activity was assessed using long-term activity records for 50 professional operators representing arable and orchard cropping systems in Greece, Lithuania, and the UK. Exposure was estimated using the harmonised Agricultural Operator Exposure Model, and risk was quantified as a point of departure index (PODI) using the lowest no observed (adverse) effect level. Use of substances with known/possible endocrine activity was common, with 43 of the 50 operators applying at least one such active substance on more than 50% of spray days; at maximum, one UK operator sprayed five such active substances and 10 such co-formulants in a single day. At 95th percentile, total exposure was largest in the UK orchard system (0.041 × 10-2 mg kg bw-1 day-1) whereas risk was largest in the Greek cropping systems (PODI 0.053 × 10-1). All five cropping systems had instances indicating potential for risk when expressed at a daily resolution (maximum PODI 1.2-10.7). Toxicological data are sparse for co-formulants, so combined risk from complex mixtures of active substances and co-formulants may be larger in reality.
Fulltext How does exposure to pesticides vary in space and time for residents living near to treated orchards?

Wong HL, Garthwaite DG, Ramwell CT, Brown CD

Environ Sci Pollut Res Int, 2017 Dec;24(34):26444-26461.
PMID: 28948535 DOI: 10.1007/s11356-017-0064-5

This study investigated changes over 25 years (1987-2012) in pesticide usage in orchards in England and Wales and associated changes to exposure and risk for resident pregnant women living 100 and 1000 m downwind of treated areas. A model was developed to estimate aggregated daily exposure to pesticides via inhaled vapour and indirect dermal contact with contaminated ground, whilst risk was expressed as a hazard quotient (HQ) based on estimated exposure and the no observed (adverse) effect level for reproductive and developmental effects. Results show the largest changes occurred between 1987 and 1996 with total pesticide usage reduced by ca. 25%, exposure per unit of pesticide applied slightly increased, and a reduction in risk per unit exposure by factors of 1.3 to 3. Thereafter, there were no consistent changes in use between 1996 and 2012, with an increase in number of applications to each crop balanced by a decrease in average application rate. Exposure per unit of pesticide applied decreased consistently over this period such that values in 2012 for this metric were 48-65% of those in 1987, and there were further smaller decreases in risk per unit exposure. All aggregated hazard quotients were two to three orders of magnitude smaller than one, despite the inherent simplifications of assuming co-occurrence of exposure to all pesticides and additivity of effects. Hazard quotients at 1000 m were 5 to 16 times smaller than those at 100 m. There were clear signals of the impact of regulatory intervention in improving the fate and hazard profiles of pesticides used in orchards in England and Wales over the period investigated.
Topical Versus Intravenous Tranexamic Acid in Patients Undergoing Cardiac Surgery: The DEPOSITION Randomized Controlled Trial

Lamy A, Sirota DA, Jacques F, Poostizadeh A, Noiseux N, Efremov S, et al.

Circulation, 2024 Oct 22;150(17):1315-1323.
PMID: 38587333 DOI: 10.1161/CIRCULATIONAHA.124.069606

BACKGROUND: Although intravenous tranexamic acid is used in cardiac surgery to reduce bleeding and transfusion, topical tranexamic acid results in lower plasma concentrations compared with intravenous tranexamic acid, which may lower the risk of seizures. We aimed to determine whether topical tranexamic acid reduces the risk of in-hospital seizure without increasing the risk of transfusion among cardiac surgery patients.
METHODS: We conducted a multicenter, double dummy, blinded, randomized controlled trial of patients recruited by convenience sampling in academic hospitals undergoing cardiac surgery with cardiopulmonary bypass. Between September 17, 2019, and November 28, 2023, a total of 3242 patients from 16 hospitals in 6 countries were randomly assigned (1:1 ratio) to receive either intravenous tranexamic acid (control) through surgery or topical tranexamic acid (treatment) at the end of surgery. The primary outcome was seizure, and the secondary outcome was red blood cell transfusion. After the last planned interim analysis, when 75% of anticipated participants had completed follow up, the data and safety monitoring board recommended to terminate the trial, and upon unblinding, the operations committee stopped the trial for safety.
RESULTS: Among 3242 randomized patients (mean age, 66.0 years; 77.7% male), in-hospital seizure occurred in 4 of 1624 patients (0.2%) in the topical group, and 11 of 1628 patients (0.7%) in the intravenous group (absolute risk difference, -0.5% [95% CI, -0.9 to 0.03]; P=0.07). Red blood cell transfusion occurred in 570 patients (35.1%) in the topical group and in 433 (26.8%) in the intravenous group (absolute risk difference, 8.3% [95% CI, 5.2-11.5]; P=0.007). The absolute risk difference in transfusion of ≥4 units of red blood cells in the topical group compared with the intravenous group was 8.2% (95% CI, 3.4-12.9).
CONCLUSIONS: Among patients undergoing cardiac surgery, topical administration of tranexamic acid resulted in an 8.3% absolute increase in transfusion without reducing the incidence of seizure, compared with intravenous tranexamic acid.
REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03954314.