159 research outputs found
Atrazine and cancer incidence among pesticide applicators in the agricultural health study (1994-2007).
No full textAtrazine is a triazine herbicide used widely in the United States. Although it is an animal carcinogen, the mechanism in rodents does not appear to operate in humans. Few epidemiologic studies have provided evidence for an association
Environ Health Perspect
No full textBackground:Growing evidence suggests that pesticide use may contribute to respiratory symptoms.Objective:We evaluated the association of currently used pesticides with allergic and non-allergic wheeze among male farmers.Methods:Using the 2005\ue2\u20ac\u201c2010 interview data of the Agricultural Health Study, a prospective study of farmers in North Carolina and Iowa, we evaluated the association between allergic and non-allergic wheeze and self-reported use of 78 specific pesticides, reported by \ue2\u2030\ua5 1% of the 22,134 men interviewed. We used polytomous regression models adjusted for age, BMI, state, smoking, and current asthma, as well as for days applying pesticides and days driving diesel tractors. We defined allergic wheeze as reporting both wheeze and doctor-diagnosed hay fever (n = 1,310, 6%) and non-allergic wheeze as reporting wheeze but not hay fever (n = 3,939, 18%); men without wheeze were the referent.Results:In models evaluating current use of specific pesticides, 19 pesticides were significantly associated (p < 0.05) with allergic wheeze (18 positive, 1 negative) and 21 pesticides with non-allergic wheeze (19 positive, 2 negative); 11 pesticides were associated with both. Seven pesticides (herbicides: 2,4-D and simazine; insecticides: carbaryl, dimethoate, disulfoton, and zeta-cypermethrin; and fungicide pyraclostrobin) had significantly different associations for allergic and non-allergic wheeze. In exposure\ue2\u20ac\u201cresponse models with up to five exposure categories, we saw evidence of an exposure\ue2\u20ac\u201cresponse relationship for several pesticides including the commonly used herbicides 2,4-D and glyphosate, the insecticides permethrin and carbaryl, and the rodenticide warfarin.Conclusions:These results for farmers implicate several pesticides that are commonly used in agricultural and residential settings with adverse respiratory effects.Citation:Hoppin JA, Umbach DM, Long S, London SJ, Henneberger PK, Blair A, Alavanja M, Beane Freeman LE, Sandler DP. 2017. Pesticides are associated with allergic and non-allergic wheeze among male farmers. Environ Health Perspect 125:535\ue2\u20ac\u201c543;\ue2\u20ac\u201ahttp://dx.doi.org/10.1289/EHP315Z01 CP010119/CP/NCI NIH HHS/United StatesZ01 ES025041/ES/NIEHS NIH HHS/United States27384423PMC538198
Environ Health Perspect
No full textBackground:Increased pesticide concentrations in house dust in agricultural areas have been attributed to several exposure pathways, including agricultural drift, para-occupational, and residential use.Objective:To guide future exposure assessment efforts, we quantified relative contributions of these pathways using meta-regression models of published data on dust pesticide concentrations.Methods:From studies in North American agricultural areas published from 1995 to 2015, we abstracted dust pesticide concentrations reported as summary statistics [e.g., geometric means (GM)]. We analyzed these data using mixed-effects meta-regression models that weighted each summary statistic by its inverse variance. Dependent variables were either the log-transformed GM (drift) or the log-transformed ratio of GMs from two groups (para-occupational, residential use).Results:For the drift pathway, predicted GMs decreased sharply and nonlinearly, with GMs 64% lower in homes 250 m versus 23 m from fields (interquartile range of published data) based on 52 statistics from seven studies. For the para-occupational pathway, GMs were 2.3 times higher [95% confidence interval (CI): 1.5, 3.3; 15 statistics, five studies] in homes of farmers who applied pesticides more recently or frequently versus less recently or frequently. For the residential use pathway, GMs were 1.3 (95% CI: 1.1, 1.4) and 1.5 (95% CI: 1.2, 1.9) times higher in treated versus untreated homes, when the probability that a pesticide was used for the pest treatment was 1\ue2\u20ac\u201c19% and \ue2\u2030\ua5 20%, respectively (88 statistics, five studies).Conclusion:Our quantification of the relative contributions of pesticide exposure pathways in agricultural populations could improve exposure assessments in epidemiologic studies. The meta-regression models can be updated when additional data become available.Citation:Deziel NC, Beane Freeman LE, Graubard BI, Jones RR, Hoppin JA, Thomas K, Hines CJ, Blair A, Sandler DP, Chen H, Lubin JH, Andreotti G, Alavanja MC, Friesen MC. 2017. Relative contributions of agricultural drift, para-occupational, and residential use exposure pathways to house dust pesticide concentrations: meta-regression of published data. Environ Health Perspect 125:296\ue2\u20ac\u201c305;\ue2\u20ac\u201ahttp://dx.doi.org/10.1289/EHP426Z01 CP010119/CP/NCI NIH HHS/United StatesZ01 ES049030/ES/NIEHS NIH HHS/United States27458779PMC533219
Methyl bromide exposure and cancer risk in the Agricultural Health Study.
No full textMethyl bromide is a genotoxic soil fumigant with high acute toxicity, but unknown human carcinogenicity. Although many countries have reduced methyl bromide use because of its ozone depleting properties, some uses remain in the United States and other countries, warranting further investigation of human health effects
Environment and genetics in lung cancer etiology (EAGLE): a novel population-based case-control study of lung cancer
No full textEAGLE is a large population-based case-control study designed to investigate the genetic and environmental determinants of lung cancer, smoking persistence, survival and therapy efficacy through combined analysis of genetic, environmental, clinical, and behavioral data. Field activities have recently concluded. Lung cancer cases were enrolled from 13 hospitals within the Lombardy region of Italy. The healthy controls were randomly selected from the same residential area of the lung cancer cases. The participation rate was high, 85% in cases and 73% in controls. The study includes 2,117 incident lung cancer cases, both males (78%) and females (22%) of Italian nationality, ages 35 to 79 years old, with verified lung cancer of any histological type, and 2,120 healthy population-based controls matched to cases by age, gender, and residence. Adenocarcinoma was the most frequent histology subtype overall (38%) and in never smokers (62%), and differed by sex (50% in females and 35% in males, overall). Interestingly, bronchoalveolar carcinoma showed the highest frequency in former smokers (53%) compared to current smokers (26%) and never smokers (21%). In contrast, all other histological subtypes, particularly small cell and large cell, had higher frequency in current smokers. Stage I tumors were more frequent in former (49%) than current (43%) smokers, while later stages were more frequent in current smokers. We collected extensive epidemiological, behavioral, and clinical data, as well as multiple biospecimens from virtually all lung cancer cases and controls. Tissue specimens, including multiple fresh “normal” lung tissue and tumor samples, were collected from surgical cases. As expected, tobacco smoking was associated with lung cancer (OR=5.0, 95% CI=4.0-6.1, and OR=11.0, 95% CI=8.8-13.6, in former and current smokers, respectively, when compared with never smokers and adjusting for matching variables). Initial analyses show that family history of cancer in first-degree relatives (OR=1.3, 95% CI=1.1-1.4), and low education level (p=0.003, test for trend, from elementary to post-graduate education) are risk factors for lung cancer in EAGLE, even after adjustment for smoking and matching variables. We are exploring the role of passive smoking, sex, occupation, diet, willingness to participate in the study, and other factors in the association with lung cancer, and behavioral data (Fagerstrom index, measures of depression, anxiety, and personality) in relation to smoking persistence. Extensive genetic investigations are also underway. This study will help answer many questions related to lung cancer etiology
Otoci Iž i Rava na starim kartama
No full textExhibition Pax Anamarija, G&V Line Jadera, Zadar – Iž – Rava, 16–26 May 2014
The National Museum Zadar (Cultural-historical collection of the Island of Iž) and the University of Zadar prepared the exhibition Islands Iž and Rava on Old Maps on the occasion of the International Museum Day. The exhibition was set on a passenger ship Anamarija owned by company G &V Line Jadera which connects islands Iž and Rava with Zadar. Visitors, mostly passengers on that route and on the Zadar – Sali – Zadar route with the same ship could see the exhibition from May 16 to 26, 2014. Considering that 200 small catalogues were printed containing an introduction and a list of exhibits and that more catalogues had to be printed, it can be assumed that the exhibition of old maps was very interesting to inhabitants of Iž and Rava, as well as other people who wanted to see how those islands were represented on maps in the past. Vladimir Alavanja provided the idea for the exhibition, and its form and location were arranged with Josip Faričić from the Department of Geography of the University of Zagreb. Two passenger saloons aboard Anamarija were chosen as the location of the exhibition in order to present the exhibits to the inhabitants and frequent travellers from Iž to Rava in the way that the maps were contextualized in the space they represent. The exhibits were placed as sections of high-quality prints of 30 selected maps and charts. Sections of old maps were printed on a high-quality paper, framed and hanged in place of curtains on ships windows. Art historian Koraljka Alavanja conceived such an artistic arrangement.Izložba M/B Anamarija, G&V Line Jadera, Zadar – Iž – Rava, 16–26. svibnja 2014.
Narodni muzej Zadar (Kulturno-povijesna zbirka otoka Iža) i Sveučilište u Zadru u povodu Međunarodnog dana muzeja priredili su izložbu Otoci Iž i Rava na starim kartama. Izložba je postavljena na putničkom linijskom brodu Anamarija tvrtke G &V Line Jadera kojim se održava jedna od redovitih brodskih pruga koja povezuje otoke Iž i Ravu sa Zadrom. Posjetitelji, najvećim dijelom putnici na toj pruzi te na pruzi Zadar – Sali – Zaglav koja se održava istim brodom, mogli su je razgledati od 16. do 26. svibnja 2014. S obzirom na to da je otisnuto 200 malih kataloga s uvodnikom i popisom eksponata i da je kataloge trebalo dotiskati, može se pretpostaviti da je izložba starih karata izazvala velik interes među Ižanima i Ravljanima, ali i svima drugima koji su htjeli pogledati kako su to ti hrvatski otoci bili prikazivani na kartama u prošlosti. Ideju za postavljanje izložbe dao je kustos Narodnog muzeja u Zadru Vladimir Alavanja, a oblik i mjesto izložbe dogovorili su spomenuti kustos i Josip Faričić s Odjela za geografiju Sveučilišta u Zadru. Za mjesto izlože odabrana su dva putnička salona u brodu Anamarija kako bi se eksponati približili stanovnicima te čestim putnicima s Iža i Rave i kako bi se stare karte na osobit način kontekstualizirale u prostoru koji prikazuju. Eksponati su postavljeni u obliku isječaka kvalitetnih preslika 30 odabranih geografskih i pomorskih karata. Isječci starih karata otisnuti su na kvalitetnom papiru, uokvireni i ovješeni umjesto zastora na brodskim prozorskim staklima. Takav likovni postav osmislila je povjesničarka umjetnosti Koraljka Alavanja
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No full textIn Argentina, horticultural production requires intensive labor and continuous application of pesticides, in a labor context poorly regulated by the State. Aims: To analyze pesticide exposure and self-perceived health conditions of horticulturists, according to living and working conditions in horticultural farms in the Food Region of Córdoba (FRC).
Population-based descriptive correlational study (2013-2019), in n=209 horticulturists pesticides applicators of pesticides in the FRC (95% confidence level); the sample was completed in two stages, the first conducted by the Group of Environmental Epidemiology of Cancer and other Chronic Diseases (n=137), and the second (n=72) together with the Observatory of Peri-urban Urban Agriculture and Agroecology (INTA). A survey translated and adapted from the Agricultural Health Study (Alavanja et al., 1996; Bonner & Alavanja, 2005) was implemented, whose reliability yielded a Cronbach\u27s α of 0.95 (Lantieri et al., 2009). Sociodemographic information, productive practices, history of pesticides exposure and self-perceived health conditions were collected. Descriptive statistics, hypothesis testing and multiple logistic regression analysis were used, using Stata-v15 software. Informed consent was implemented.
The mean age was 45 years (SD 13), 70% resided on the farm and 52% reported family work. The average seniority of pesticide application was 18.79 years (SD 11.38), only 27% of the workers used adequate protection when applying pesticides. Also, 21% of them reported having accidents with pesticides (splashing, ingestion, etc); 58% reported symptoms related to the application, neurological (40%) and irritative (38%) among others. 42% reported one or more tracer illnesses. The probability of reporting illnesses increased among workers with more than 20 years in the task (OR=3.048; p ≤ 0.05 ) and among those who expressed presenting accidents with pesticides (OR=2.85; p ≤0.05); while the report of symptoms was higher among horticulturists who manifested accidents (OR= 5.71; p ≤0.05).
A high prevalence of symptoms and tracer diseases associated with prolonged use and accidents with pesticides was reported.En Argentina, la producción hortícola requiere mano de obra intensiva y aplicación continua de plaguicidas, en un contexto laboral poco regulado por el Estado. Objetivo: Analizar la exposición a plaguicidas y condiciones de salud autopercibida de horticultoras/es, según las condiciones de vida y trabajo en las quintas hortícolas de la Región Alimentaria de Córdoba (RAC).
Estudio descriptivo correlacional de base poblacional (2013-2019), en n=209 horticultoras/es agroaplicadoras/es de plaguicidas de la RAC (nivel confianza del 95%); muestra completada en dos etapas, la primera realizada por el Grupo de Epidemiología Ambiental del Cáncer y otras enfermedades Crónicas (n=137), y la segunda (n=72) junto al Observatorio de Agricultura Urbana Periurbana y Agroecología (INTA). Se implementó una encuesta traducida y adaptada del Agricultural Health Agricultural Health Study (Alavanja Alavanja et al., 1996; Bonner & Alavanja, 2005), cuya confiabilidad arrojó un α de Cronbach de 0,95 (Lantieri et al., 2009). Se relevó información sociodemográfica, prácticas productivas, historia de exposición a plaguicidas y condiciones de salud autopercibida. Estadísticas descriptivas, test de hipótesis y análisis de regresión logística múltiple fueron utilizados, empleando el Software Stata-v15. Se implementó consentimiento informado.
La edad promedio fue 45 años (DE 13), el 70% residía en la quinta y el 52% reportó trabajo familiar. La antigüedad promedio de aplicación de plaguicidas fue 18,79 años (DE 11,38), sólo 27% de las/os trabajadoras/es utilizó protección adecuada al aplicar plaguicidas. Asimismo, 21% de ellas/os refirió sufrir accidentes con plaguicidas (salpicaduras, ingestión, etc); 58% reportó síntomas relacionados con la aplicación, neurológicos (40%) e irritativos (38%) entre otros. El 42% reportó una o más enfermedades trazadoras. La probabilidad de reporte de enfermedades aumentó entre trabajadores con más de 20 años en la tarea (OR=3,048; p ≤ 0,05 ) y entre quienes expresaron presentar accidentes con plaguicidas (OR = 2,85; p ≤0,05); mientras que el reporte de síntomas fue mayor entre horticultoras/es que manifestaron accidentes (OR= 5,71; p ≤0,05).
Se reportó una alta prevalencia de síntomas y enfermedades trazadoras asociadas al uso prolongado y accidentes con plaguicidas.
Environment And Genetics in Lung cancer Etiology (EAGLE) study: An integrative population-based case-control study of lung cancer
No full textBackground: Lung cancer is the leading cause of cancer mortality worldwide. Tobacco smoking is its primary cause, and yet the precise molecular alterations induced by smoking in lung tissue that lead to lung cancer and impact survival have remained obscure. A new framework of research is needed to address the challenges offered by this complex disease.
Methods/Design: We designed a large population-based case-control study that combines a traditional molecular epidemiology design with a more integrative approach to investigate the dynamic process that begins with smoking initiation, proceeds through dependency/smoking persistence, continues with lung cancer development and ends with progression to disseminated disease or response to therapy and survival. The study allows the integration of data from multiple sources in the same subjects (risk factors, germline variation, genomic alterations in tumors, and clinical endpoints) to tackle the disease etiology from different angles. Before beginning the study, we conducted a phone survey and pilot investigations to identify the best approach to ensure an acceptable participation in the study from cases and controls. Between 2002 and 2005, we enrolled 2101 incident primary lung cancer cases and 2120 population controls, with 86.6% and 72.4% participation rate, respectively, from a catchment area including 216 municipalities in the Lombardy region of Italy. Lung cancer cases were enrolled in 13 hospitals and population controls were randomly sampled from the area to match the cases by age, gender and residence. Detailed epidemiological information and biospecimens were collected from each participant, and clinical data and tissue specimens from the cases. Collection of follow-up data on treatment and survival is ongoing.
Discussion: EAGLE is a new population-based case-control study that explores the full spectrum of lung cancer etiology, from smoking addiction to lung cancer outcome, through examination of epidemiological, molecular, and clinical data. We have provided a detailed description of the study design, field activities, management, and opportunities for research following this integrative approach, which allows a sharper and more comprehensive vision of the complex nature of this disease. The study is poised to accelerate the emergence of new preventive and therapeutic strategies with potentially enormous impact on public health
Factors associated with self-reported, pesticide-related visits to health care providers in the agricultural health study
No full textTo investigate factors associated with pesticide-related visits to health care providers (i.e., doctor or hospital visits), responses to self-administered questionnaires received from 35,879 licensed restricted-use pesticide applicators participating in the Agricultural Health Study were analyzed. (In Iowa, applicators are actually certified, whereas in North Carolina they are licensed; for ease of reference, the term license will be used for both states in this paper.) The cohort reported a total of more than 10.9 million pesticide-application days. These applications were associated with one or more pesticide-related health care visits by 2,214 applicators (7.0% of the applicator cohort for whom health care visit data were available). The odds of a pesticide-related health care visit were increased for commercial applicators compared to private applicators [odds ratio ( 0 R = 1. 77; 95% confidence interval (CI), 1.52-2.06) and for applicators who used insecticides 70 times or more in their lifetime compared to those who used insecticides less frequently (OR = 1.43; CI, 1.26-1.63). After adjusting for the number of applications in a logistic regression model, significantly higher odds of health care visits were observed among North Carolina applicators compared to Iowa applicators (OR= 1.35; CI, 1.17- 1.52), among applicators who mixed their own pesticides (OR = 1.65; CI, 1.22- 2.23), and among applicators who personally repaired their pesticide application equipment at least once per year (OR= 1.12; Cl, 1.06-1.25). Significantly lower odds were found among female versus male applicators (OR = 0.68; Cl, 0.46-0.99) and among applicators who graduated from high school versus those who did not (OR= 0.82; CI, 0.71-0.94 for high school graduates and OR = 0.79; CI, 0.68-0.91 for those with at least some college). Several methods of pesticide application to crops, seed, or stored grain were also associated with significantly elevated odds ratios of health care visits. These observations suggest that several steps can be taken to reduce the number of health care visits resulting from occupational exposure to pesticides. The implications of this pattern of pesticide-related health care visits may have etiologic implications for cancer and other chronic diseases.This article is published as Alavanja, M. C., Dale P. Sandler, Cheryl J. McDonnell, Charles F. Lynch, Margaret Pennybacker, Shelia Hoar Zahm, Jay Lubin et al. "Factors associated with self-reported, pesticide-related visits to health care providers in the agricultural health study." Environmental health perspectives 106, no. 7 (1998): 415. </p
Screening, identification, structure-activity, and mode of action studies with new antitrypanosomal leads of plant and fungal origin
No full textHuman African trypanosomiasis (HAT) is a neglected disease caused by the protozoan Trypanosoma brucei, which is transmitted during blood-feeding tsetse fly bites. The disease is endemic covering 36 sub-Saharan African countries and mainly impacts poor people living in remote areas, for which satisfactory treatment does not exist. As such, this protozoal disease would never be viewed as viable target market for the pharmaceutical industry. Therefore, it is referred to as a neglected disease. Chemotherapy remains the principal treatment for HAT and is based on four drugs: suramin, pentamidine, melarsoprol, eflornithine, and a recent approved eflornithine-nifurtimox combination. Reported severe side effects (e.g. melarsoprol), treatment failures of up to 25%, administration difficulties, and expensive medication urgently demand for safe, orally administered drugs, that are effective against both stages of HAT. Natural sources like plants and fungi provide a rich biological diversity with unique pharmacophores created by evolution and are therefore potential sources to discover such new drugs.
This thesis describes the search of new natural products (NPs) from nature. Over the last seven years we collected 724 plants and 64 fungi. The material was subsequently extracted and tested in vitro against T. b. rhodesiense, Plasmodium falciparum (the causative agent of malaria), Leishmania donovani (leishmaniasis), and T. cruzi (Chagas disease) to find potential hits. From the total 2151 extracts, 17.9% showed activity of more than 50% at 4.81 µg/mL test concentration against at least one parasite, and 3.4% showed potency of more than 50% at 0.81 µg/mL test concentration, respectively. Overall the plant extracts had six times higher "hit-rates" (15.3%) than the fungi extracts (2.6%), both resulting in high potencies against T. b. rhodesiense and P. falciparum. Yet, with up to 5 millions fungi, which outnumber higher plants by 16:1, the kingdom remains a relatively poorly studied source.
One of the antitrypanosomal hits was a dichloromethane (DCM) extract of the cornflower Centaurea salmantica with a growth inhibition of 61% tested at 4.81 µg/mL against T. b. rhodesiense. HPLC-based activity profiling led to the identification of the sesquiterpene lactone (STL) cynaropicrin (CYN), which was the first plant NP to show in vivo efficacy in T. b. rhodesiense infected mice, treated i.p. at 10 mg/kg/b.i.d. for four consecutive days. Despite of more than 10'000 known STLs is a better understanding of the structural features, which contribute to activity, expedient. The established structure-activity relationship (SAR) study included 18 natural STLs and demonstrated that antitrypanosomal and cytotoxic effect depended on their a,ß-unsaturated enone moieties. Many bioactivities of STLs have been attributed to a nucleophilic Michael-addition of these functional motifs to biological thiols. Considering that trypanosomes depend on their unique trypanothione-based redox system to deal with oxidative stress and to maintain a reducing intracellular milieu and that CYN contains reactive exocyclic a,ß-unsaturated methylenes, we anticipated that the mechanism of action depended on a direct interference with glutathione (GSH) and trypanothione (T(SH)2) in the cells. After 5 min. of CYN's exposure to trypanosomes, the intracellular thiol pool was completely depleted and a GS-CYN-monoadduct as well as a T(S-CYN)2-bisadduct were formed. This led to apoptosis of the trypanosomes over 40 min. linked to phenotype transformations from the typical slender to a stumpy-like form. Additionally, ornithine quantification studies by tandem mass spectroscopy (MS/MS) showed that ornithine decarboxylase (ODC) is a potential secondary target for CYN.
To improve CYN's pharmacokinetic (PK) profile the a,ß-unsaturated exocyclic double bond at the lactone was masked to create an amine prodrug with increased aqueous solubility and reduced unspecific binding to biological thiols. Through subsequent bioactivation the prodrug would be converted back to CYN and it would display a higher concentration on the target side. The lead optimization did not reward any better antitrypanosomal in vivo efficacy after oral application, but the prodrug had an improved in vivo cytotoxic profile. Further PK studies with other orally applied STL amino derivatives are needed to demonstrate if the use of amino STLs as prodrugs is a reasonable approach to improve STLs suitability as antitrypanosomal drug
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