Factors influencing occupational exposure to pyrethroids and glyphosate: An analysis of urinary biomarkers in Malaysia, Uganda and the United Kingdom.

BACKGROUND: Long-term exposure to pesticides is often assessed using semi-quantitative models. To improve these models, a better understanding of how occupational factors determine exposure (e.g., as estimated by biomonitoring) would be valuable. METHODS: Urine samples were collected from pesticide applicators in Malaysia, Uganda, and the UK during mixing/application days (and also during non-application days in Uganda). Samples were collected pre- and post-activity on the same day and analysed for biomarkers of active ingredients (AIs), including synthetic pyrethroids (via the metabolite 3-phenoxybenzoic acid [3-PBA]) and glyphosate, as well as creatinine. We performed multilevel Tobit regression models for each study to assess the relationship between exposure modifying factors (e.g., mixing/application of AI, duration of activity, personal protective equipment [PPE]) and urinary biomarkers of exposure. RESULTS: From the Malaysia, Uganda, and UK studies, 81, 84, and 106 study participants provided 162, 384 and 212 urine samples, respectively. Pyrethroid use on the sampling day was most common in Malaysia (n = 38; 47%), and glyphosate use was most prevalent in the UK (n = 93; 88%). Median pre- and post-activity 3-PBA concentrations were similar, with higher median concentrations post-compared to pre-activity for glyphosate samples in the UK (1.7 to 0.5 µg/L) and Uganda (7.6 to 0.8 µg/L) (glyphosate was not used in the Malaysia study). There was evidence from individual studies that higher urinary biomarker concentrations were associated with mixing/application of the AI on the day of urine sampling, longer duration of mixing/application, lower PPE protection, and less education/literacy, but no factor was consistently associated with exposure across biomarkers in the three studies. CONCLUSIONS: Our results suggest a need for AI-specific interpretation of exposure modifying factors as the relevance of exposure routes, levels of detection, and farming systems/practices may be very context and AI-specific.

Impact of occupational pesticide exposure assessment method on risk estimates for prostate cancer, non-Hodgkin's lymphoma and Parkinson's disease: results of three meta-analyses.

Assessment of occupational pesticide exposure in epidemiological studies of chronic diseases is challenging. Biomonitoring of current pesticide levels might not correlate with past exposure relevant to disease aetiology, and indirect methods often rely on workers' imperfect recall of exposures, or job titles. We investigated how the applied exposure assessment method influenced risk estimates for some chronic diseases. In three meta-analyses the influence of exposure assessment method type on the summary risk ratio (sRR) of prostate cancer (PC) (25 articles), non-Hodgkin's lymphoma (NHL) (29 articles) and Parkinson's disease (PD) (32 articles) was investigated. Exposure assessment method types analysed were: group-level assessments (eg, job titles), self-reported exposures, expert-level assessments (eg, job-exposure matrices) and biomonitoring (eg, blood, urine). Additionally, sRRs were estimated by study design, publication year period and geographic location where the study was conducted. Exposure assessment method types were not associated with statistically significant different sRRs across any of the health outcomes. Heterogeneity in results varied from high in cancer studies to moderate and low in PD studies. Overall, case-control designs showed significantly higher sRR estimates than prospective cohort designs. Later NHL publications showed significantly higher sRR estimates than earlier. For PC, studies from North America showed significantly higher sRR estimates than studies from Europe. We conclude that exposure assessment method applied in studies of occupational exposure to pesticides appears not to have a significant effect on risk estimates for PC, NHL and PD. In systematic reviews of chronic health effects of occupational exposure to pesticides, epidemiological study design, publication year and geographic location, should primarily be considered.

Assessment of pesticide safety knowledge and practices in Vietnam: A cross-sectional study of smallholder farmers in the Mekong Delta.

Over the past three decades, the Vietnamese Mekong Delta has experienced a significant increase in agricultural productivity, partly achieved through increased agrochemical use. To abate negative effects on human and environmental health, several national programs were launched to enhance safer pesticide use. This study aimed to assess the patterns and relationships of official sustainable agriculture educational programs, pesticide safety knowledge, and practices of smallholder farmers in the Mekong Delta. A cross-sectional survey was conducted with 400 smallholder farmers from three communes in Thoi Lai district (Can Tho province) from March to May 2020. Twenty-four questions on pesticide safety knowledge and practices were used to identify traits using latent class analysis. Adjusted generalized linear regression was used to assess determinants of pesticide safety knowledge and estimate associations of pesticide safety knowledge with pesticide practices. 96.2% of participants have used at least one WHO class II pesticide during the past year while the use of specific personal protective equipment was limited mainly due to unavailability (37.0%) or discomfort (83.0%). High education (Odds Ratio (OR), 95% Confidence Interval; 3.84, 1.70-9.45), exposure to official educational programs (1.87, 1.13-3.12), peer-to-peer knowledge exchange (3.58, 2.18-6.00), and learning from governmental extension services (2.31, 1.14-4.98) were positively associated with increased pesticide safety knowledge. Compared to poor practices, pesticide safety knowledge was increasingly positively associated with intermediate (1.65, 1.02-2.66) and good pesticide practices (8.96, 2.58-31.12). These findings highlight the importance of school education and educational programs, access to PPE, and addressing discomforts of PPE to improve the protection of farmers from pesticide exposures. Simultaneously, pesticide market authorization processes should be reconsidered to promote the authorization of less toxic products. Further in-depth studies on the nature of pesticides used, nonuse of personal protective equipment, and effectiveness of educational programs will further define leverage points for safer pesticide use.

Organophosphate and carbamate insecticide exposure is related to lung function change among smallholder farmers: a prospective study.

INTRODUCTION AND AIM: Exposure to some insecticides may cause airway obstruction, but existing evidence is limited by cross-sectional designs and inadequate confounder control. We investigated the relation between organophosphate and carbamate insecticides and pulmonary function in a prospective study accounting for important confounders. METHODS: In a cohort of 364 smallholder farmers in Uganda (69% women), participants underwent pre-bronchodilator spirometry at baseline (September/October 2018) and at two follow-up visits (November/December 2018 and January/February 2019). Exposure to carbamate and organophosphate insecticides was assessed using haemoglobin-adjusted erythrocyte acetylcholinesterase (AChE/Hb). Less than 3% of participants were lost to follow-up. We calculated Z-scores for FEV1, FVC and FEV1/FVC using the Global Lung Function Initiative equations. Data were analysed in linear mixed and fixed effect models accounting for family relationships and repeated measures of exposure and outcome. RESULTS: Low AChE/Hb was significantly associated with low FEV1 Z-score in both unadjusted and adjusted analyses. Compared with individuals with AChE/Hb 25.90 U/g (50th percentile, reference), those with lower AChE/Hb 24.50 U/g (35th percentile) had mean FEV1 Z-score 0.045 (0.003 to 0.087) lower, and persons with higher AChE/Hb 27.30 U/g (65th percentile) had a mean FEV1 Z-score 0.043 (-0.002 to 0.087) higher compared with the reference. Similar, but numerically smaller and statistically non-significant effects were seen for Z-scores of FVC and FEV1/FVC. CONCLUSION: Exposure to organophosphate and carbamate insecticides may lead to lung function decline. Our results add to the growing evidence of health effects in relation to exposure to organophosphate and carbamate insecticides, underlining the importance of minimising exposure.

Variability and predictors of weekly pesticide exposure in applicators from organic, sustainable and conventional smallholder farms in Costa Rica.

OBJECTIVE: Estimates of pesticide exposure among applicators from low- and middle-income countries (LMICs) are scarce, and exposure assessment methods are sometimes costly or logistically unfeasible. We examined the variability in weeklong pesticide exposure among applicators in Costa Rica and its predictors. METHODS: We conducted a cross-sectional survey among 221 pesticide applicators from organic, sustainable and conventional farms in 2016. We administered structured questionnaires to assess pesticide application practices at two time points (4-6 weeks apart). We adapted an existing algorithm to fit the context of smallholders and derive weekly pesticide exposure scores. We used linear mixed-effect models to examine within-worker and between-worker score variability. We then identified sociodemographic and occupational predictors of weekly pesticide exposure scores. RESULTS: We observed high within-worker and between-worker variability in weekly pesticide exposures (eg, up to 180-fold and 70-fold differences in average weekly exposures within and between workers, respectively; intraclass correlation coefficient=0.4). Applicators working on conventional and sustainable farms had exposure scores twofold and 1.5-fold higher than those working in organic farms, respectively. Farm workers who received training on pesticide use had weekly pesticide exposure scores of 33% (95% CI 1% to 55%) lower than those who did not receive any training. CONCLUSIONS: In this study of applicators from smallholder farms in Costa Rica, we determined the importance of collecting questionnaire data on self-reported pesticide use repeatedly due to its high variability within workers and absence of application records. Our questionnaire-based exposure algorithm could allow the calculation of semiquantitative estimates of average pesticide exposure for applicators from other LMICs.

Systematic review of methods used to assess exposure to pesticides in occupational epidemiology studies, 1993-2017.

OBJECTIVE: Numerous exposure assessment methods (EAM) exist for investigating health effects of occupational exposure to pesticides. Direct (eg, biomonitoring) and indirect methods (eg, self-reported exposures) are however associated with degrees of exposure misclassification. We systematically reviewed EAM in studies of occupational pesticide exposure. METHODS: We searched for articles reporting observational epidemiological studies in MEDLINE and Embase published 1993 to 2017. The relative frequency of EAM was analysed according to EAM type (direct and indirect methods), health outcome, study design, study location (country) and specificity of assessment. Temporal trends in EAM were analysed. RESULTS: In 1298 included articles 1521 EAM occurrences were documented. Indirect EAM (78.3%), primarily self-reported exposures (39.3%) and job titles assessments (9.5%), were mainly applied in case-control studies (95.0%), in high-income countries (85.0%) and in studies of doctor-diagnosed health outcomes (>85%). Direct EAM (20.8%), primarily biomonitoring of blood (15.6%) or urine (4.7%), were predominantly applied in cross-sectional studies (29.8%), in lower middle-income countries (40.9%) and in studies of neurological (50.0%) outcomes. Between 1993 to 2017 no distinct time trends regarding the ratio indirect to direct methods was seen. Within the category of indirect methods use of self-reported exposures and job exposure matrices increased while assessments by job titles and registers decreased. The use of algorithms showed no trend. The specificity of pesticide assessment increased since studies assessing exposure by using job title as a proxy declined. Assessments of type of pesticide increased. CONCLUSION: Over the last 25 years, the ratio (5:1) of indirect to direct EAM applied in articles on occupational pesticide epidemiology stayed relatively constant; changes were mainly attributable to increasing use of self-reported exposures and job exposure matrices. This review, combined with studies assessing EAM validity, will inform on magnitudes of exposure misclassification and help improve the quality of studies on occupational pesticides exposure.

Exposure to cholinesterase inhibiting insecticides and blood glucose level in a population of Ugandan smallholder farmers.

OBJECTIVES: The risk of diabetes mellitus may be elevated among persons exposed to some pesticides, including cholinesterase-inhibiting insecticides (organophosphates and carbamates). The objective of this study was to investigate how acetylcholinesterase activity was associated with mean blood glucose levels among smallholder farmers in Uganda. METHODS: We conducted a short-term follow-up study among 364 smallholder farmers in Uganda. Participants were examined three times from September 2018 to February 2019. At each visit, we measured glycosylated haemoglobin A (HbA1c) as a measure of long-term average blood glucose levels. Exposure to organophosphate and carbamate insecticides was quantified using erythrocyte acetylcholinesterase normalised by haemoglobin (AChE/Hb). For a subgroup of participants, fasting plasma glucose (FPG) was also available. We analysed HbA1c and FPG versus AChE/Hb in linear mixed and fixed effect models adjusting for age, sex, physical activity level, and consumption of fruits and vegetables, alcohol and tobacco. RESULTS: Contrary to our hypothesis, our mixed effect models showed significant correlation between low AChE/Hb and low HbA1c. Adjusted mean HbA1c was 0.74 (95% CI 0.17 to 1.31) mmol/mol lower for subjects with AChE/Hb=24.3 U/g (35th percentile) compared with subjects with AChE/Hb=25.8 U/g (50th percentile). Similar results were demonstrated for FPG. Fixed effect models showed less clear correlations for between-phase changes in AChE/Hb and HbA1c. CONCLUSIONS: Our results do not clearly support a causal link between exposure to cholinesterase-inhibiting insecticides and elevated blood glucose levels (expressed as HbA1c and FPG), but results should be interpreted with caution due to the risk of reverse causality.

Different aspects of electronic media use, symptoms and neurocognitive outcomes of children and adolescents in the rural Western Cape region of South Africa.

BACKGROUND: Electronic media use is increasing in low- and middle-income countries, thus we aim to investigate the prevalence of different aspects of e-media use and its association to symptoms and neurocognitive outcomes in rural South Africa. METHODS: In the cohort study, "Child health Agricultural Pesticide study in South Africa (CapSA)", of 1001 children and adolescents, aged 9-16 years, we enquired at baseline about the following aspects of e-media use: (1) call duration (2) total screen time (3) night-time awakenings from mobile phone use, and (4) Mobile Phone Problematic Use. Four health outcomes were included: sleep disturbance, health related quality of life (HRQoL), headaches and cognitive performance, assessed through six tests on domains of attention, memory and processing speed, using the iPad-based software, CAmbridge Neuropsychological Test Automated Battery (CANTAB). Linear regression analysis adjusted for relevant confounders was conducted with categorized exposure variables low, medium and high use. RESULTS: One third of the cohort (31.8%) are mobile phone users reporting average duration of calls per day up to 75 min (mean = 2.5 mins; SD = 8.9 mins). Amongst 46% of the cohort who report e-media device use, total screen time ranged from 1 min to 441 min (mean = 28.3; SD = 53.0). Findings Amongst those reporting regular night-time awakenings (≥1 times per week) from mobile phones, HRQol declined by 2.9 (95% CI: -6.1, 0.3), the sleep disturbance score increased by 2.0 (1.1, 2.9) units and headache impact score significantly increased by 5.4 (2.6; 8.2) units compared to non-exposed. Cognitive performance scores tended to be slightly improved mostly in moderate e-media users. The reaction response speed was consistently improved amongst all four exposure groups compared to non-users. CONCLUSION: These results are among the first from Africa on benefits and risks associated with e-media use. Our findings imply that with regard to the education of adolescents, a vigilant balance is needed to profit from the beneficial effects of moderate e-media use on cognition, while preventing the negative side effects for HRQoL, sleep disturbance and headache severity.

Manganese exposure and working memory-related brain activity in smallholder farmworkers in Costa Rica: Results from a pilot study.

Main sources of manganese (Mn) in the general population are diet and drinking water. Mn is also found in ethylene bisdithiocarbamate (EBDC) fungicides used in agriculture or emitted into the air by ferromanganese plants and welding fumes, which can be additional environmental and occupational sources of exposure. High occupational Mn exposure has been linked with motor, behavioral, and cognitive impairment, but its effects on neural function remain poorly understood. We conducted a functional neuroimaging study in a sample of 48 farmworkers in Zarcero County, Costa Rica, an agricultural region where EBDC fungicides are sprayed. We measured Mn concentrations in farmworkers' toenails (n = 40 farmworkers) and hair (n = 33 farmworkers), and recorded brain activity in the dorsolateral prefrontal cortex during a letter-retrieval working memory task using functional near-infrared spectroscopy (fNIRS). We estimated exposure-outcome associations using multivariable linear regression models adjusted for age and education level. Geometric mean (geometric standard deviation) toenail and hair Mn concentrations were 0.40 µg/g (3.52) and 0.24 µg/g (3.54), respectively. We did not find strong evidence that Mn concentrations were associated with working memory-related brain activity in this sample of farmworkers; we also found null associations between working memory task accuracy and brain activity. However, our small sample size may have limited our ability to detect small effect sizes with statistical precision. Our study demonstrates that fNIRS can be a useful and feasible tool in environmental epidemiology for examining the effects of toxicants, like Mn, on neural function. This may prove to be important for elucidating neuropathological pathways that underlie previously reported associations of elevated Mn exposure with neurotoxic effects.

Daily variation of heavy metal contamination and its potential sources along the major urban wastewater channel in Kampala, Uganda.

Heavy metal pollution from untreated industrial wastewater has become a major concern to the environment and public health in many rapidly growing cities in low-income countries. Previous studies on heavy metals of urban wastewater systems have focused on long-term (weekly or seasonal) variations, while only few studies investigated short-term (daily) variation to capture potential bulk discharges. To monitor and enforce wastewater discharge regulations and reduce industrial pollution, a better understanding of the short-term variation of these pollutants and industrial discharge practices is needed. The aim of this study is to assess the daily variation of heavy metals and physicochemical parameters along the major urban wastewater system in Kampala, Uganda. Over 1 week, daily water samples were collected at 16 locations and analyzed for lead (Pb), mercury (Hg), copper (Cu), and chromium (Cr) and a range of physicochemical parameters. Additionally, 25 key informant interviews with industries were administered to investigate their potential to contaminate the environment. Among 78 water samples, 29 exceeded the national standards for Pb (> 0.1 mg/L) and one for Hg (> 0.01 mg/L). High daily variation and peak concentrations were detected which are likely due to industries retaining their effluents and discharging them irregularly. Although 24 industries used heavy metals in their manufacturing processes and are likely to discharge heavy metals, only ten industries had a wastewater treatment system in place. Our results show that repeated measurements of heavy metals over short time intervals are needed to capture their high daily variation in an urban wastewater system. Furthermore, there is an urgent need to register industries and to assess their effluent composition in order to select appropriate wastewater management measures.

A prospective cohort study of school-going children investigating reproductive and neurobehavioral health effects due to environmental pesticide exposure in the Western Cape, South Africa: study protocol.

BACKGROUND: Research on reproductive health effects on children from low-level, long-term exposure to pesticides currently used in the agricultural industry is limited and those on neurobehavioral effects have produced conflicting evidence. We aim at investigating the association between pesticide exposure on the reproductive health and neurobehavior of children in South Africa, by including potential relevant co-exposures from the use of electronic media and maternal alcohol consumption. METHODS: The design entails a prospective cohort study with a follow-up duration of 2 years starting in 2017, including 1000 school going children between the ages of 9 to 16 years old. Children are enrolled with equal distribution in sex and residence on farms and non-farms in three different agricultural areas (mainly apple, table grapes and wheat farming systems) in the Western Cape, South Africa. The neurobehavior primary health outcome of cognitive functioning was measured through the iPad-based CAmbridge Neuropsychological Test Automated Battery (CANTAB) including domains for attention, memory, and processing speed. The reproductive health outcomes include testicular size in boys and breast size in girls assessed in a physical examination, and blood samples to detect hormone levels and anthropometric measurements. Information on pesticide exposure, co-exposures and relevant confounders are obtained through structured questionnaire interviews with the children and their guardians. Environmental occurrence of pesticides will be determined while using a structured interview with farm owners and review of spraying records and collection of passive water and air samples in all three areas. Pesticide metabolites will be analysed in urine and hair samples collected from the study subjects every 4 months starting at baseline. DISCUSSION: The inclusion of three different agricultural areas will yield a wide range of pesticide exposure situations. The prospective longitudinal design is a further strength of this study to evaluate the reproductive and neurobehavioural effects of different pesticides on children. This research will inform relevant policies and regulatory bodies to improve the health, safety and learning environments for children and families in agricultural settings.

Microbial and chemical contamination of water, sediment and soil in the Nakivubo wetland area in Kampala, Uganda.

The reuse of domestic and industrial wastewater in urban settings of the developing world may harm the health of people through direct contact or via contaminated urban agricultural products and drinking water. We assessed chemical and microbial pollutants in 23 sentinel sites along the wastewater and faecal sludge management and reuse chain of Kampala, Uganda. Water samples were examined for bacteria (thermotolerant coliforms (TTCs), Escherichia coli and Salmonella spp.) and helminth eggs. Physico-chemical parameters were determined. Water, sediment and soil samples and edible plants (yams and sugar cane) were tested for heavy metals. Water samples derived from the Nakivubo wetland showed mean concentrations of TTCs of 2.9 × 10(5) colony-forming units (CFU)/100 mL. Mean E. coli was 9.9 × 10(4) CFU/100 mL. Hookworm eggs were found in 13.5% of the water samples. Mean concentrations of iron (Fe), copper (Cu) and cadmium (Cd) were 21.5, 3.3 and 0.14 mg/L, respectively. In soil samples, we found a mean lead (Pb) concentration of 132.7 mg/L. In yams, concentrations of Cd, chromium (Cr) and Pb were 4.4, 4.0 and 0.2 mg/L, while the respective concentrations in sugar cane were 8.4, 4.3 and 0.2 mg/L. TTCs and E. coli in the water, Pb in soil, and Cd, Cr and Pb in the plants were above national thresholds. We conclude that there is considerable environmental pollution in the Nakivubo wetland and the Lake Victoria ecosystem in Kampala. Our findings have important public health implications, and we suggest that a system of sentinel surveillance is being implemented that, in turn, can guide adequate responses.

Occupational exposure to pesticides and neurobehavioral outcomes. Impact of different original and recalled exposure measures on the associations.

BACKGROUND: Several measures of occupational exposure to pesticides have been used to study associations between exposure to pesticides and neurobehavioral outcomes. This study assessed the impact of different exposure measures for glyphosate and mancozeb on the association with neurobehavioral outcomes based on original and recalled self-reported data with 246 smallholder farmers in Uganda. METHODS: The association between the 6 exposure measures and 6 selected neurobehavioral test scores was investigated using linear multivariable regression models. Exposure measures included original exposure measures for the previous year in 2017: (i) application status (yes/no), (ii) number of application days, (iii) average exposure-intensity scores (EIS) of an application and (iv) number of EIS-weighted application days. Two additional measures were collected in 2019: (v) recalled application status and (vi) recalled EIS for the respective periods in 2017. RESULTS: Recalled applicator status and EIS were between 1.2 and 1.4 times more frequent and higher for both pesticides than the original application status and EIS. Adverse associations between the different original measures of exposure to glyphosate and 4 neurobehavioral tests were observed. Glyphosate exposure based on recalled information and all mancozeb exposure measures were not associated with the neurobehavioral outcomes. CONCLUSIONS: The relation between the different original self-reported glyphosate exposure measures and neurobehavioral test scores appeared to be robust. When based on recalled exposure measures, associations observed with the original exposure measures were no longer present. Therefore, future epidemiological studies on self-reported exposure should critically evaluate the potential bias towards the null in observed exposure-response associations.

Association of pesticide exposure with respiratory health outcomes and rhinitis in avocado farmworkers from Michoacán, Mexico.

BACKGROUND: A growing literature suggests associations between occupational pesticide exposure and respiratory health. In this study, we aimed to examine the association of exposure to insecticides, fungicides, and herbicides, individually and as a mixture, with respiratory health outcomes and rhinitis in avocado farmworkers from Michoacán, Mexico. MATERIAL AND METHODS: We conducted a cross-sectional study of 105 avocado farmworkers between May and August 2021. We quantified 12 insecticide, fungicide, and herbicide metabolites in urine samples collected during two study visits (8-10 weeks apart). We collected survey data on self-reported pesticide use during the 12 months prior to the baseline survey and estimated annual exposure-intensity scores (EIS) using a semi-quantitative exposure algorithm. We also assessed respiratory symptoms, including wheezing, chest tightness, wheezing after exercise, and night cough. We used generalized linear regression models to examine associations of individual urinary metabolite concentrations and annual EIS with respiratory health outcomes and rhinitis. Mixture effects were assessed using Bayesian Weighted Quantile Sum (BWQS) regression. RESULTS: After adjusting for multiple comparisons, we observed mostly null associations of individual pesticide metabolite concentrations and annual EIS with the outcomes of interest. However, in BWQS analyses, we found evidence of a mixture association of urinary pesticide metabolites with increased odds of night cough (OR: 5.34, 95 % CrI: 1.67, 20.62). Pyrethroid metabolites 3-phenoxybenzoic acid and cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid were the main contributors to this association (43 %). CONCLUSIONS: Our findings indicate that exposure to a mixture of pesticides, particularly pyrethroid insecticides, may be associated with night cough in avocado farmworkers.

Evaluating and Enhancing an Educational Intervention to Reduce Smallholder Farmers' Exposure to Pesticides in Uganda Through a Digital, Systematic Approach to Behavior Change: Protocol for a Cluster-Randomized Controlled Trial.

BACKGROUND: Smallholder farmers receive educational interventions on safe pesticide handling by governmental agencies, industries, or nongovernmental organizations to reduce exposure risks. However, existing educational interventions have limited effects on changing behaviors. Targeting psychosocial determinants of behavior change in educational interventions through theory- and evidence-based approaches may enhance their effectiveness. OBJECTIVE: We aim at describing the intervention development and study design of a 3-arm cluster-randomized controlled trial to assess the effects in improving safe pesticide handling and reducing pesticide exposure of (1) an existing educational intervention and (2) a newly developed SMS text messaging intervention based on the Risks, Attitudes, Norms, Abilities, and Self-regulation (RANAS) behavior change approach. METHODS: We enrolled 539 Ugandan smallholder farmers in 12 clusters (subcounties). The clusters, each with 45 farmers, were randomly allocated to one of the three arms: (1) educational intervention, (2) educational intervention+RANAS-based SMS text messages, or (3) control group. The educational intervention comprised a 2-day workshop that targeted multiple aspects of safe pesticide handling, whereas the SMS text messages targeted the use of personal protective equipment (PPE) and were based on the RANAS approach. For intervention development in this study, this approach includes identifying psychosocial determinants of PPE use at baseline and selecting behavior change techniques to target them in SMS text messages. The primary outcomes of the study are (1) pesticide knowledge, attitude, and practice scores indicating performance throughout the educational intervention; and (2) frequency of PPE use. Secondary outcomes are the RANAS-based behavioral determinants of PPE use, the frequency of glove use, algorithm-based pesticide exposure intensity scores, and signs and symptoms of pesticide poisoning. The outcomes were assessed in structured interviews before the intervention (baseline) and at the 12-month follow-up. The effect of the interventions among the arms will be analyzed using the intervention arms and baseline measures as predictors and the follow-up measures as outcomes in linear multivariable mixed models including the clusters as random effects. The mediating psychosocial determinants of the interventions will be assessed in multiple mediation models. RESULTS: The study was conducted from 2020 to 2021-baseline interviews were conducted in October 2020, and the educational intervention was delivered in November 2020. The RANAS-based SMS text messages were developed based on the baseline data for relevant behavioral determinants of PPE use and sent between February 2021 and September 2021. Follow-up interviews were conducted in October 2021. Overall, 539 farmers were enrolled in the study at baseline; 8.3% (45/539) were lost to follow-up by the end of the study. CONCLUSIONS: This study will contribute to a better understanding of the effectiveness and behavior change mechanisms of educational interventions by using an experimental, cluster-randomized study design to improve pesticide handling among smallholder farmers. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number (ISRCTN) 18237656; https://doi.org/10.1186/ISRCTN18237656. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55238.

Association of pesticide exposure with neurobehavioral outcomes among avocado farmworkers in Mexico.

BACKGROUND AND AIM: To date, few studies have focused on the health effects of pesticide exposure among avocado farmworkers. We examined the association of exposure to insecticides, fungicides, and herbicides with cognitive and mental health outcomes among these avocado workers from Michoacan, Mexico. MATERIALS AND METHODS: We conducted a cross-sectional study of 105 avocado farmworkers between May and August 2021. We collected data on self-reported pesticide use during the 12 months prior to the baseline survey and estimated annual exposure-intensity scores (EIS) using a semi-quantitative exposure algorithm. We calculated specific gravity adjusted average concentrations of 12 insecticide, fungicide, or herbicide metabolites measured in urine samples collected during two study visits (8-10 weeks apart). We assessed participants' cognitive function and psychological distress using the NIH Toolbox Cognition Battery and the Brief Symptom Inventory 18 (BSI-18), respectively. We examined individual associations of EIS and urinary pesticide metabolites with neurobehavioral outcomes using generalized linear regression models. We also implemented Bayesian Weighted Quantile Sum (BWQS) regression to evaluate the association between a pesticide metabolite mixture and neurobehavioral outcomes. RESULTS: In individual models, after adjusting for multiple comparisons, higher concentrations of hydroxy-tebuconazole (OH-TEB, metabolite of fungicide tebuconazole) were associated with higher anxiety (IRR per two-fold increase in concentrations = 1.26, 95% CI:1.08, 1.48) and Global Severity Index (GSI) (IRR = 1.89, 95% CI:1.36, 2.75) scores, whereas higher concentrations of 3,5,6-trichloro-2-pyridinol (TCPy, metabolite of chlorpyrifos) were associated with lower GSI scores (IRR = 0.69, 95% CI: 0.56, 0.85). In BWQS analyses, we found evidence of a mixture association of urinary pesticide metabolites with higher anxiety (IRR = 1.72, 95% CrI: 1.12, 2.55), depression (IRR = 4.60, 95% CrI: 2.19, 9.43), and GSI (IRR = 1.99, 95% CrI: 1.39, 2.79) scores. OH-TEB and hydroxy-thiabendazole (metabolite of fungicide thiabendazole) combined contributed 54%, 40%, and 54% to the mixture effect in the anxiety symptoms, depression symptoms, and overall psychological distress models, respectively. CONCLUSIONS: We found that exposure to tebuconazole and thiabendazole, fungicides whose effects have been rarely studied in humans, may be associated with increased psychological distress among avocado farmworkers. We also observed that exposure to chlorpyrifos may be associated with decreased psychological distress.

Child exposure to organophosphate and pyrethroid insecticides measured in urine, wristbands, and household dust and its implications for child health in South Africa: A panel study.

Background: Children in agricultural areas are exposed to organophosphate (OP) and pyrethroid (PYR) insecticides. This explorative study investigated child exposure to OPs and PYRs, comparing temporal and spatial exposure variability within and among urine, wristbands, and dust samples. Methods: During spraying season 2018, 38 South African children in two agricultural areas (Grabouw/Hex River Valley) and settings (farm/village) participated in a seven-day study. Child urine and household dust samples were collected on days 1 and 7. Children and their guardians were wearing silicone wristbands for seven days. Intraclass correlation coefficients (ICCs) evaluated temporal agreements between repeated urine and dust samples, Spearman rank correlations (Rs) evaluated the correlations among matrices, and linear mixed-effect models investigated spatial exposure predictors. A risk assessment was performed using reverse dosimetry. Results: Eighteen OPs/PYRs were targeted in urine, wristbands, and dust. Levels of chlorpyrifos in dust (ICC = 0.92) and diethylphosphate biomarker in urine (ICC = 0.42) showed strong and moderate temporal agreement between day 1 and day 7, respectively. Weak agreements were observed for all others. There was mostly a weak correlation among the three matrices (Rs = -0.12 to 0.35), except for chlorpyrifos in dust and its biomarker 3,5,6-trichloro-2-pyridinol in urine (Rs = 0.44). No differences in exposure levels between living locations were observed. However, 21% of the urine biomarker levels exceeded the health-risk threshold for OP exposure. Conclusions: Observed high short-term variability in exposure levels during spraying season highlights the need for repeated sampling. The weak correlation between the exposure matrices points to different environmental and behavioral exposure pathways. Exceeding risk thresholds for OP should be further investigated.

Contaminants of Emerging Concern (CECs) and Male Reproductive Health: Challenging the Future with a Double-Edged Sword.

Approximately 9% of couples are infertile, with half of these cases relating to male factors. While many cases of male infertility are associated with genetic and lifestyle factors, approximately 30% of cases are still idiopathic. Contaminants of emerging concern (CECs) denote substances identified in the environment for the first time or detected at low concentrations during water quality analysis. Since CEC production and use have increased in recent decades, CECs are now ubiquitous in surface and groundwater. CECs are increasingly observed in human tissues, and parallel reports indicate that semen quality is continuously declining, supporting the notion that CECs may play a role in infertility. This narrative review focuses on several CECs (including pesticides and pharmaceuticals) detected in the nearshore marine environment of False Bay, Cape Town, South Africa, and deliberates their potential effects on male fertility and the offspring of exposed parents, as well as the use of spermatozoa in toxicological studies. Collective findings report that chronic in vivo exposure to pesticides, including atrazine, simazine, and chlorpyrifos, is likely to be detrimental to the reproduction of many organisms, as well as to sperm performance in vitro. Similarly, exposure to pharmaceuticals such as diclofenac and naproxen impairs sperm motility both in vivo and in vitro. These contaminants are also likely to play a key role in health and disease in offspring sired by parents exposed to CECs. On the other side of the double-edged sword, we propose that due to its sensitivity to environmental conditions, spermatozoa could be used as a bioindicator in eco- and repro-toxicology studies.

Self-reported and urinary biomarker-based measures of exposure to glyphosate and mancozeb and sleep problems among smallholder farmers in Uganda.

OBJECTIVE: We aim to showcase the impact of applying eight different self-reported and urinary biomarker-based exposure measures for glyphosate and mancozeb on the association with sleep problems in a study among 253 smallholder farmers in Uganda. METHODS: The questionnaire-based exposure measures included: (1) the number of application days of any pesticide in the last 7 days (never, 1-2; >2 days) and six glyphosate and mancozeb-specific measures: (2) application status over the last 12 months (yes/no), (3) recent application status (never, last 7 days and last 12 months), (4) the number of application days last 12 months, (5) average exposure-intensity scores (EIS) and (6) EIS-weighted number of application days in last 12 months. Based on 384 repeated urinary biomarker concentrations of ethylene thiourea (ETU) and glyphosate from 84 farmers, we also estimated (7) average biomarker concentrations for all 253 farmers. Also in the 84 farmers the measured pre-work and post-work biomarker concentrations were used (8). Multivariable logistic regression models were used to assess the association between the exposure measures and selected Medical Outcomes Study Sleep Scale (MOS-SS) indices (6-item, sleep inadequacy and snoring). RESULTS: We observed positive associations between (1) any pesticide application in the last 7 days with all three MOS-SS indices. Glyphosate application in the last 7 days (3) and mancozeb application in the last 12 months (3) were associated with the 6-item sleep problem index. The estimated average urinary glyphosate concentrations showed an exposure-response association with the 6-item sleep problem index and sleep inadequacy in the same direction as based on self-reported glyphosate application in the last 7 days. In the analysis with the subset of 84 farmers, both measured and modelled post-work urinary glyphosate concentration showed an association with snoring. CONCLUSIONS: Self-reported, estimated average biomarker concentrations and measured urinary biomarker exposure measures of glyphosate and mancozeb showed similar exposure-response associations with sleep outcomes.

Barriers to evidence use for sustainability: Insights from pesticide policy and practice.

Calls for supporting sustainability through more and better research rest on an incomplete understanding of scientific evidence use. We argue that a variety of barriers to a transformative impact of evidence arises from diverse actor motivations within different stages of evidence use. We abductively specify this variety in policy and practice arenas for three actor motivations (truth-seeking, sense-making, and utility-maximizing) and five stages (evidence production, uptake, influence on decisions, effects on sustainability outcomes, and feedback from outcome evaluations). Our interdisciplinary synthesis focuses on the sustainability challenge of reducing environmental and human health risks of agricultural pesticides. It identifies barriers resulting from (1) truth-seekers' desire to reduce uncertainty that is complicated by evidence gaps, (2) sense-makers' evidence needs that differ from the type of evidence available, and (3) utility-maximizers' interests that guide strategic evidence use. We outline context-specific research-policy-practice measures to increase evidence use for sustainable transformation in pesticides and beyond.