Health Effects of Pesticide Exposure in Latin American and the Caribbean Populations: A Scoping Review.

BACKGROUND: Multiple epidemiological studies have shown that exposure to pesticides is associated with adverse health outcomes. However, the literature on pesticide-related health effects in the Latin American and the Caribbean (LAC) region, an area of intensive agricultural and residential pesticide use, is sparse. We conducted a scoping review to describe the current state of research on the health effects of pesticide exposure in LAC populations with the goal of identifying knowledge gaps and research capacity building needs. METHODS: We searched PubMed and SciELO for epidemiological studies on pesticide exposure and human health in LAC populations published between January 2007 and December 2021. We identified 233 publications from 16 countries that met our inclusion criteria and grouped them by health outcome (genotoxicity, neurobehavioral outcomes, placental outcomes and teratogenicity, cancer, thyroid function, reproductive outcomes, birth outcomes and child growth, and others). RESULTS: Most published studies were conducted in Brazil (37%, n=88) and Mexico (20%, n=46), were cross-sectional in design (72%, n=167), and focused on farmworkers (45%, n=105) or children (21%, n=48). The most frequently studied health effects included genotoxicity (24%, n=62) and neurobehavioral outcomes (21%, n=54), and organophosphate (OP) pesticides were the most frequently examined (26%, n=81). Forty-seven percent (n=112) of the studies relied only on indirect pesticide exposure assessment methods. Exposure to OP pesticides, carbamates, or to multiple pesticide classes was consistently associated with markers of genotoxicity and adverse neurobehavioral outcomes, particularly among children and farmworkers. DISCUSSION: Our scoping review provides some evidence that exposure to pesticides may adversely impact the health of LAC populations, but methodological limitations and inconsistencies undermine the strength of the conclusions. It is critical to increase capacity building, integrate research initiatives, and conduct more rigorous epidemiological studies in the region to address these limitations, better inform public health surveillance systems, and maximize the impact of research on public policies. https://doi.org/10.1289/EHP9934.

Mycotoxin Exposure in Children through Breakfast Cereal Consumption in Chile.

Mycotoxins are unavoidable contaminants produced by fungi in food, especially grains. This study aimed to measure the occurrence and levels of total aflatoxins (AFs); ochratoxin A (OTA); zearalenone (ZEN); fumonisins B1, B2, and B3 (FUM); deoxynivalenol (DON); and T-2/HT-2 toxins in the four most commonly consumed breakfast cereals in Chile and to assess mycotoxin exposure and risk in children aged 2 to 13 years due to cereal consumption. In this study, a total of 110 batches with three subsamples of the four brands were sampled in supermarkets from November 2019 to June 2021. Samples were analyzed by Veratox® ELISA (Neogen). Exposure was assessed by estimated daily intake (EDI) considering the levels found in a modified lower bound (mLB) and upper bound (UB). Risk was estimated by margin of exposure (MOE) in the case of OTA and AFs and hazard quotient (HQ) for the rest of the mycotoxins. No T2/HT2 toxins were detected. Few samples had quantifiable levels of ZEN, FUM, and DON except for brand 1, with a mean (standard deviation, SD) of 54 (20), 1552 (351), and 706 (218) ng/g, respectively. In addition, three FUM samples and one DON sample had values over the Chilean regulation. Brands 2, 3, and 4 had quantifiable levels of AFs, with mean (SD) values of 1.3 (0.1), 2.1 (0.6), and 1.9 (0.4) ng/g, respectively. Brand 3 had quantifiable levels of OTA, with a mean (SD) of 2.3 (0.4) ng/g. Estimated exposure indicated a risk of AFs in all scenarios, and of FUM for brand 1 consumption, OTA and DON for brand 3 consumption, and OTA for brand 4 consumption in the mLB worst-case scenario. In general, mycotoxin levels were below the Chilean regulatory limits, but most of them were above the EU regulation for processed cereal-based food in young children. Because the risk was higher in the 2- to 5-year-old children, we recommend special regulations for this group in Chile.

A preliminary study on aflatoxin exposure by urine biomonitoring in Chile.

We assessed the occurrence of aflatoxin M1 (AFM1) in urine in a sample of the MAUCO population-based cohort (n = 120) using an enzyme-linked immune sorbent assay (ELISA) kit specially designed for the analysis of AFM1 in urine. We found AFM1 in the urine of 59% of the participants (> limit of detection), with 12% of the samples being over the limit of quantification. The mean of the quantifiable samples was 0.66 (± 0.35) ng/mg adjusted creatinine, ranging from 0.31 to 1.39 ng/mg creatinine. The mean probable daily intake (PDI) of AFB1 was 0.23 (± 0.37) ng/kg bw according to the upper bound (UB), being significantly higher in women and 0.14 (± 0.23) ng/kg bw in the modified lower bound (mLB) approach, ranging from 0.01 to 1.98 ng/kg bw. The risk of AFB1 was assessed with the margin of exposure (MOE) approach estimated at 2800 in the mean mLB and 1733 in the mean UB. According to the MOE values obtained in this study, aflatoxin B1 exposure must be considered a public health concern and must be taken as a priority for food risk management.

Assessment of Mycotoxin Exposure in a Rural County of Chile by Urinary Biomarker Determination.

Aflatoxin B1 (AFB1), ochratoxin A (OTA), zearalenone (ZEN), and deoxynivalenol (DON) are frequent mycotoxins that may cause carcinogenic, mutagenic, estrogenic, or gastrointestinal effects. The aim of this study was to assess the exposure to and risk from AFB1, OTA, ZEN, and DON in 172 participants of the Maule Cohort (MAUCO) by a biomarker analysis in urine and to associate their exposure with food consumption and occupation. Mycotoxins in the first morning urine were analyzed by solid-phase extraction and quantified by Ultra-High-Performance Liquid Chromatography with a mass-mass detector. Participants' information regarding food consumption, occupation, and other characteristics was obtained from a baseline and 2-year follow-up survey of the cohort. The prevalence and mean levels of mycotoxins in the urine were as follows: DON 63%, 60.7 (±78.7) ng/mL; AFB1 8%, 0.3 (±0.3) ng/mL; α-zearalenol (α-ZEL) 4.1%, 41.8 (±115) ng/mL; ß-ZEL 3.5%, 17.4 (±16.1) ng/mL; AFM1 2%, 1.8 (±1.0) ng/mL; OTA 0.6% (1/172), 1.3 ng/mL; and ZEN 0.6%, 1.1 ng/mL. These results were translated into exposures of DON, ZEN, and aflatoxins of public health concern. Participants who consumed coffee and pepper the day before had a significantly greater presence of DON (OR: 2.3, CI95 1.17-4.96) and total ZEL (OR: 14.7, CI95 3.1-81.0), respectively, in their urine. Additionally, we observed associations between the habitual consumption of beer and DON (OR: 2.89, CI95 1.39-6.42). Regarding the levels of mycotoxins and the amount of food consumed, we found correlations between DON and nuts (p = 0.003), total ZEL and cereals (p = 0.01), and aflatoxins with capsicum powder (p = 0.03) and walnuts (p = 0.03). Occupation did not show an association with the presence of mycotoxins in urine.

Levels of Polychlorinated Dibenzo-p-Dioxins/Furans (PCDD/Fs) and Dioxin-Like Polychlorinated Biphenyls (DL-PCBs) in Human Breast Milk in Chile: A Pilot Study.

Persistent organic pollutants (POPs) are organic compounds that resist biochemical degradation, moving long distances across the atmosphere before deposition occurs. Our goal was to provide up-to-date data on the levels of polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) in breast milk from Chilean women and to estimate the exposure of infants due to breast milk consumption. In Chile, we conducted a cross-sectional study based on methodologies proposed by the WHO, with a sample of 30 women recruited from three defined areas: 10 from the Arica Region (urban; Arica and Parinacota Region), 10 from Coltauco (rural; O'Higgins Region), and 10 from Molina (40% rural; Maule Region). High-resolution gas chromatography coupled with high-resolution mass spectrometry (HRGC/HRMS) was performed on pooled samples from each area. We calculated equivalent toxic concentrations (WHO-TEQ) based on the current WHO Toxic Equivalency Factors (TEF). The minimum and maximum values of ∑ PCDDs/Fs + DL-PCBs-TEQ were 4.317 pg TEQ/g fat in Coltauco and 6.31 pg TEQ/g fat in Arica. Molina had a total TEQ of 5.50 pg TEQ/g fat. The contribution of PCDD/Fs was approximately five-fold higher than that of DL-PCBs. The Estimated Daily Intake (EDI) of ∑ PCDDs/Fs + DL-PCBs based on the three pooled samples ranged between 6.71 and 26.28 pg TEQ/kg body weight (bw)/day, with a mean intake of 16.11 (±6.71) pg TEQ/kg bw/day in breastfed children from 0 to 24 months old. These levels were lower than those reported in international studies. Despite the fact that the observed levels were low compared to those in most industrialized countries, the detection of a variety of POPs in breast milk from Chilean women indicates the need for follow-up studies to determine whether such exposures during childhood could represent a health risk in adulthood.

[Pesticide exposure in Chile and population health: urgency for decision making]. / Exposición a plaguicidas en Chile y salud poblacional: urgencia para la toma de decisiones.

In the last 25 years, Chile has had an expanding role as an agro-export country in the global economy, with efficient rates of productivity in the region, based on the technological development of agriculture, with of large monocultures whose productivity depends on the intensive application of agrochemicals. This form of agriculture has also lacked efficient regulations and surveillance, so it is difficult to estimate the real magnitude of the exposed population and its effects on health in the short or long term. This systematic review compiles the epidemiological evidence generated from studies conducted in several regions of Chile regarding pesticide exposure and health effects. Of the total number of articles, 50% included agricultural workers, 25% children, and 25% women of childbearing age, with the greatest effects being the neurotoxic (54%), genotoxic (31%) and reproductive (15%). The evidence collected shows that in Chile the levels of exposure to pesticides in the general and occupational population are higher than international studies levels. It is urgent to protect the health of both the occupational and general population and especially children through a stricter control of the sale and use of pesticides, with comprehensive surveillance systems in environmental health and educational actions in the social and cultural context of rural communities. It is a priority to strengthen research with national relevance on health effects, and strictly restrict the use of pesticides already prohibited in developed countries due to their high level of risk to human and environmental health.

Occurrence of relevant mycotoxins in food commodities consumed in Chile.

The aims of this study were to analyse the occurrence of aflatoxins, aflatoxin M1 (AFM1), fumonisins, ochratoxin A (OTA), patulin (PAT), zearalenone (ZEN) and deoxynivalenol (DON) in foodstuffs consumed in Chile between 2008 and 2017 and to estimate the contribution of main contaminated foodstuff in human exposure by the probable daily intake (PDI) estimation. In 9 years of surveillance, 2020 food samples were analysed with an occurrence of 18.2% and with 2.7% of the samples being over the Chilean regulation. The occurrence of mycotoxins in food were 16% for aflatoxins, 6% for AFM1, 30% for OTA, 12% for DON, 7% for PAT, 21% for fumonisins and 2% for ZEN. The estimated median PDI of DON because of bread consumption was 129.2 ng/kg bw/day for children and 96.0 ng/kg bw/day in adults. Median PDI because of capsicum consumption was 0.006 ng/kg bw/day for OTA and 0.005 ng/kg bw/day for aflatoxins. Median PDI of aflatoxins was estimated at 0.02 ng/kg bw/day for spices and 0.04 ng/kg bw/day for nuts consumption. In children, the median PDI of AFM1 for dairy consumption was 0.07 ng/kg bw/day. The derived margin of exposure (MoE) values ranged from 1133 to 8500 suggested that aflatoxins would be of public health concern. The PDI of the other mycotoxins did not show a health risk. This is the first survey of mycotoxins in food made in Chile; further research is needed to improve surveillance and guidelines based on national risk assessments and considering sensitive population groups.

Caligus rogercresseyi infestation is associated with Piscirickettsia salmonis-attributed mortalities in farmed salmonids in Chile.

Caligidosis and Piscirickettsiosis are currently the most important sanitary challenges for the Chilean salmon industry. Caligidosis is caused by the ectoparasite, Caligus rogercresseyi and Piscirickettsiosis is caused by the intracellular bacterium, Piscirickettsia salmonis. Both diseases are highly prevalent and widely distributed in farming areas in Chile. The co-occurrence of the two diseases is frequently reported on salmon farms. However, there is little epidemiological evidence as to whether these two diseases are associated and generate interactive effects. This study was undertaken to evaluate the potential effects of C. rogercresseyi infestation on P. salmonis-attributed mortalities in farmed salmonids in Chile. Using a linear regression model, the potential association between the mean abundance of adult C. rogercresseyi in a period of 10 weeks and Piscirickettsiosis cumulative mortalities observed in the following 10 weeks was evaluated, while controlling for important confounders. These two 10-week windows were set around the time-point at which Piscirickettsiosis weekly mortality exceeded 0.1% for the first time in a production cycle. We found that the mean abundance of adult C. rogercresseyi was significantly associated with the Piscirickettsiosis cumulative mortality, suggesting the two diseases have a synergistic relationship. This relationship was of the same intensity in Atlantic salmon and rainbow trout. Our findings highlight the importance of taking effective control measures for C. rogercresseyi as a part of the strategies in place to reduce P. salmonis-attributed mortalities on salmon farms in Chile.

Study protocol for the Maule Cohort (MAUCO) of chronic diseases, Chile 2014-2024.

BACKGROUND: Maule Cohort (MAUCO), a Chilean cohort study, seeks to analyze the natural history of chronic diseases in the agricultural county of Molina (40,000 inhabitants) in the Maule Region, Chile. Molina´s population is of particular interest because in the last few decades it changed from being undernourished to suffering excess caloric intake, and it currently has the highest national rates of cardiovascular diseases, stomach cancer and gallbladder cancer. Between 2009 and 2011 Molina´s poverty rate dropped from 24.1 % to 13.5 % (national average 20.4 %); in this period the county went from insufficient to almost complete basic sanitation. Despite these advances, chemical pollutants in the food and air are increasing. Thus, in Molina risk factors typical of both under-developed and developed countries coexist, generating a unique profile associated with inflammation, oxidative stress and chronic diseases. METHODS/DESIGN: MAUCO is the core project of the recently established Advanced Center for Chronic Diseases (ACCDiS), Universidad de Chile & Pontificia Universidad Católica de Chile. In this study, we are enrolling and following 10,000 adults aged 38 to 74 years over 10 years. All eligible Molina residents will be enrolled. Participants were identified through a household census. Consenting individuals answer an epidemiological survey exploring risk factors (psycho-social, pesticides, diet, alcohol, and physical activity), medical history and physical and cognitive conditions; provide fasting blood, urine, and saliva samples; receive an electrocardiogram, abdominal ultrasound and bio-impedance test; and take a hand-grip strength test. These subjects will be re-interviewed after 2, 5 and 7 years. Active surveillance of health events is in place throughout the regional healthcare system. The MAUCO Bio-Bank will store 30 to 50 aliquots per subject using an NIH/NCI biorepository system for secure and anonymous linkage of samples with data. DISCUSSION: MAUCO´s results will help design public health interventions tailored to agricultural populations in Latin America.

Spray Versus Forced Coagulation in Large Loop Excision of the Transformation Zone: A Randomized Trial.

OBJECTIVE: Large loop excision of the transformation zone (LLETZ) is the standard surgical treatment for cervical dysplasia. The optimal way to achieve local hemostasis in women undergoing LLETZ is unknown. MATERIALS AND METHODS: In a prospective, randomized trial, we compared spray coagulation and forced coagulation in women undergoing LLETZ in a 1:1 ratio. The primary endpoint was time to complete local hemostasis (TCLH). Secondary endpoints were blood loss (Δ hemoglobin before and after LLETZ), pain (numerical visual analog scale, 5-step graphical visual analog scale measured 2-3 hours after LLETZ), and perioperative/postoperative complications (intraoperative need for sutures, postoperative bleeding, infection, and unscheduled readmission). Analysis was by intention to treat. RESULTS: One hundred fifty-one women were enrolled and were eligible for analysis. Mean (SD) TCLH in 80 women with forced coagulation was 43.3 (38.5) and 28.9 (22.9) seconds in 71 women with spray coagulation (p < 0.001). The secondary endpoints blood loss (Δ hemoglobin, -0.8 [0.8] vs -0.7 [1.1]; p = 0.115), pain (numerical visual analog scale, 4.1 [0.9] vs 4.2 [0.9]; p = 0.283, graphical visual analog scale (1.9 [1.3] vs 1.8 [1.3]; p = 0.888), and perioperative/postoperative complications (6/71 [8%] vs 7/80 [9%]; p = 0.822) were comparable between the 2 arms. In a multivariate analysis, coagulation method (odds ratio = 0.18; 95% CI = 0.09-0.38; p < 0.001) and size of the cervix (odds ratio = 2.43; 95% CI = 1.16-5.15; p = 0.021) were independent predictors of TCLH. CONCLUSIONS: Spray coagulation is superior to forced coagulation in women undergoing LLETZ and should be used as the standard approach.

The case for aflatoxins in the causal chain of gallbladder cancer.

Chronic aflatoxin exposure has long been related to hepatocellular carcinoma (HCC). Recently, its association with gallbladder cancer (GBC) was postulated. Here we present the data supporting this hypothesis in Chile, the country with the highest GBC mortality worldwide with age-standardized mortality rates (ASMR) of 10.3 in women and 5.04 in men. The highest GBC rates occur in Southern Chile (ASMR=18), characterized by: high Amerindian ancestry, associated with high bile acid synthesis and gallstones; high poverty and high cereal agriculture, both associated with aflatoxin exposure. Aflatoxins have been detected in imported and locally grown foods items. We estimated population dietary exposure ranging from 0.25 to 35.0 ng/kg-body weight/day. The only report on human exposure in Chile found significantly more aflatoxin biomarkers in GBC than in controls (Odds Ratio=13.0). The hypothesis of aflatoxin-GBC causal link in the Chilean population is supported by: genetically-determined rapid cholesterol excretion and high gallstones prevalence (49.4%); low prevalence of HCC (ASMR=4.9) and low HBV infection (0.15%) the main co-factor of aflatoxins in HCC risk. If the association between aflatoxins and GBC were confirmed, public health interventions based on food regulation could have a substantial public health impact.

Characterization of Listeria monocytogenes isolates from cattle and ground beef by pulsed-field gel electrophoresis.

The aims of this study were to determine the occurrence of Listeria monocytogenes in cattle feces and ground beef, to characterize these strains by pulsed-field gel electrophoresis and to compare them to three listeria strains found in humans. Cattle from different origins (n = 250) and ground beef obtained from supermarkets (n = 40) were sampled. The results show low occurrence in cattle feces (0.4 %) but a higher presence in ground beef (37 %). An important part of the ground beef strains (80 %) had > 95 % similarity with a strain isolated from a human sporadic case and the ATCC 19115 used as control. The strain isolated from cattle feces had 93 % similarity to clone 009, previously associated with a listeriosis outbreak related to cheese. Cattle and ground beef can harbor virulent L. monocytogenes strains. Further studies in animals and animal products are needed to improve listeriosis control.

Persisting corneal erosion under cetuximab (Erbitux) treatment (epidermal growth factor receptor antibody).

PURPOSE: To report persisting corneal erosion and trichomegaly as ocular side effects of cetuximab (Erbitux) treatment, a monoclonal antibody against the epidermal growth factor (EGF) receptor. METHODS: A 62-year-old patient was treated with combined chemotherapy including cetuximab for colorectal carcinoma and showed accelerated growth of eyelashes with persistent bilateral corneal erosions resistant to conservative treatment. Topical EGF was successfully applied as an experimental treatment to antagonize the inhibitory effect of the EGF receptor antibody. RESULTS: Topical application of EGF led to rapid improvement, with complete healing of the epithelial defect after 7 (left eye) and 19 days (right eye) while application of cetuximab was continued. CONCLUSIONS: Cetuximab (Erbitux) can cause impairment of corneal wound healing as an ocular side effect. Patients concerned may benefit from application of EGF eyedrops.

The CK1 gene family: expression patterning in zebrafish development.

Protein kinase CK1 is a ser/thr protein kinase family which has been identified in the cytosol cell fraction, associated with membranes as well as in the nucleus. Several isoforms of this gene family have been described in various organisms: CK1alpha, CK1beta, CK1delta, CK1epsilon and CK1gamma. Over the last decade, several members of this family have been involved in development processes related to wnt and sonic hedgehog signalling pathways. However, there is no detailed temporal information on the CK1 family in embryonic stages, even though orthologous genes have been described in several different vertebrate species. In this study, we describe for the first time the cloning and detailed expression pattern of five CK1 zebrafish genes. Sequence analysis revealed that zebrafish CK1 proteins are highly homologous to other vertebrate orthologues. Zebrafish CK1 genes are expressed throughout development in common and different territories. All the genes studied in development show maternal and zygotic expression with the exception of CK1epsilon. This last gene presents only a zygotic component of expression. In early stages of development CK1 genes are ubiquitously expressed with the exception of CK1epsilon. In later stages the five CK1 genes are expressed in the brain but not in the same way. This observation probably implicates the CK1 family genes in different and also in redundant functions. This is the first time that a detailed comparison of the expression of CK1 family genes is directly assessed in a vertebrate system throughout development.

Delayed epithelial healing after keratoplasty for lattice corneal dystrophy.

PURPOSE: To compare the time necessary for complete epithelial healing after penetrating keratoplasty carried out for various corneal dystrophies. METHODS: In a retrospective single-center study, 679 eyes that underwent nonmechanical keratoplasty were evaluated concerning postoperative epithelial healing time. On the basis of corneal pathology, the eyes were divided into 5 groups: group 1, lattice dystrophy (n = 9); group 2, macular dystrophy (n = 16); group 3, Fuchs dystrophy (n = 207); group 4, granular dystrophy (n = 13); group 5, keratoconus (n = 434). After keratoplasty, the time necessary for complete healing of the epithelial defect was compared among the groups. RESULTS: In lattice dystrophy, 22% showed delayed healing, in contrast to 0% in granular dystrophy. Mean time necessary for healing in group 1 (8.8 +/- 9.4 days) was significantly longer than in group 2 (2.5 +/- 2.5 days, P = 0.003), group 3 (4.4 +/- 4.1 days, P = 0.09), group 4 (2.2 +/- 1.4 days, P = 0.003), and group 5 (3.1 +/- 2.7 days, P = 0.005). CONCLUSIONS: In patients with lattice dystrophy, delayed epithelial healing after penetrating keratoplasty may be anticipated. Patients should be counseled accordingly.

The CK1 gene family: expression patterning in zebrafish development

Protein kinase CK1 is a ser/thr protein kinase family which has been identified in the cytosol cell fraction, associated with membranes as well as in the nucleus. Several isoforms of this gene family have been described in various organisms: CK1 , CK1á, CK1δ, CK1å and CK1γ. Over the last decade, several members of this family have been involved in development processes related to wnt and sonic hedgehog signalling pathways. However, there is no detailed temporal information on the CK1 family in embryonic stages, even though orthologous genes have been described in several different vertebrate species. In this study, we describe for the first time the cloning and detailed expression pattern of five CK1 zebrafish genes. Sequence analysis revealed that zebrafish CK1 proteins are highly homologous to other vertebrate orthologues. Zebrafish CK1 genes are expressed throughout development in common and different territories. All the genes studied in development show maternal and zygotic expression with the exception of CK1å. This last gene presents only a zygotic component of expression. In early stages of development CK1 genes are ubiquitously expressed with the exception of CK1å. In later stages the five CK1 genes are expressed in the brain but not in the same way. This observation probably implicates the CK1 family genes in different and also in redundant functions. This is the first time that a detailed comparison of the expression of CK1 family genes is directly assessed in a vertebrate system throughout development.