Skin infections by the ectoparasitic mite Sarcoptes scabiei are a preventable source of morbidity worldwide. While scabies affects all socioeconomic sectors, it is especially prominent in the developing world where crowding, poor hygiene, and limited access to basic health care are commonplace. Mass eradication efforts of this parasite have historically been hampered by delivery and compliance issues surrounding topical standards of care. There have been advances in eradication over the last decade due to the expanded use of oral Ivermectin for the treatment and prevention of ectoparasites such as scabies. Previous research focused on various treatment aspects of the disease, yet most identified the need for basic scabies health education to accompany future studies to improve program sustainability and the overall health literacy of target populations. The Virginia College of Osteopathic Medicine sponsors a public health clinic in Veron, Dominican Republic that reports a high prevalence of scabies infections among its general patient population. The lack of any means of direct measurement, proper intervention, or control raises concerns that long-term infection may lead to multiple other secondary disease sequelae. The Veron Scabies Eradication and Education Program was designed to address this deficiency and build on previous studies related to this problem by using a novel treatment and education protocol. The purpose of this research was to identify, treat, and prevent primary and secondary health problems due to long-term scabies infection in the community of Barrio Nuevo, Veron, Dominican Republic in order to provide long-term sustainable eradication through a researcher-designed health education program and medical service protocol. Participants continued typical daily life while interventions and education were monitored to detect change over a 9-month timeline using selected measurement intervals to test multiple scabies disease and knowledge objectives and related hypotheses. Following this basic protocol, the following scabies markers were evaluated at baseline: subject demographics, scabies diagnosis and treatment history, baseline treatments and reported side effects, and scabies education pre-test results. The following scabies markers were also assessed at baseline and reassessed at 2 weeks, 1 month, 2 months, 8 months, and 9 months: risk and prevention behaviors, symptomatology, skin exam findings, and scabies education post-test results. There was a statistically significant post-intervention improvement in scabies markers when compared to pre-intervention values (p<0.05). This study demonstrated that a community scabies program involving large-scale treatment and education can provide rapid and long lasting improvements to the health of a highly endemic population. Community-wide scabies eradication is possible with the appropriate level of structure and support using low cost medication available to the health care system that serves Veron, Dominican Republic. Given the efficacy and safety profile of Ivermectin demonstrated in this study and substantiated by others, it is recommended that the Dominican Republic Ministry of Health consider adopting Ivermectin as the standard of care for scabies treatments and enforce an existing formal ban on Lindane products. The protocol from this research should be considered for adoption to provide a sustainable, practical, self-sufficient model for improved health outcomes, health behaviors, and health literacy. Future studies should replicate this research to determine validation in other settings, cultures and situations, build on the findings by exploring additional variables related to environmental risk factors, and continue to develop interventions that promote health education and enhance clinical practices. / Ph. D.

Parkinson's disease (PD) is a neurodegenerative Lewy body disorder characterized by severe motor deficits, followed by cognitive dysfunction with progression of the disease. Environmental exposure has been suggested as a possible contributor to the development of PD and this view is linked to the discovery of the nigrostriatal neurotoxin MPTP. MPTP can induce dopamine specific degeneration within the basal ganglia often resulting in motor deficits similar to PD. MPTP used in the C57BL/6 mouse is a widely used animal model of PD. The pyrethroid permethrin (PM), and the organophosphate chlorpyrifos (CPF), can produce changes in dopaminergic nigrostriatal neurons, the primary target of PD and MPTP-induced neurotoxicity. Such insecticide induced changes in the basal ganglia could exacerbate the onset or severity of PD. Chronic exposure to the metal manganese (Mn) can damage the globus pallidus (GP) of the BG, and produce motor deficits similar to PD. Since the GP is part of the BG circuitry essential for motor control, and is synaptically integrated with the nigrostriatal pathway, Mn may exacerbate MPTP-induced neurotoxicity. Because the BG is disynaptically linked to the mesocortical pathway, a dopaminergic pathway that is important for cognition, Mn induced damage in the BG could indirectly affect the mesocortical pathway as well. This study investigated the pesticides, permethrin and chlorpyrifos, and the heavy metal, manganese as possible environmental compounds that could exacerbate PD in the MPTP treated C57BL/6 mouse. The first part of this dissertation used immunohistochemistry to examine insecticide induced effets on MPTP-induced neurotoxicity in the dorsolateral striatum of the C57BL/6 mouse, the principal target of the nigrostriatal pathway. Tyrosine hydroxylase (TH) was used as a marker for loss of dopaminergic neuropil and glial fibrillary acidic protein (GFAP) was used as a marker of glial activation in the striatum. Three experiments assessed effects of 1) PM (200 mg/kg), 2) CPF (50 mg/kg) & 3) PM + CPF, on MPTP (30 mg/kg) neurotoxicity. Immunohistochemistry revealed a decrease in TH staining and an increase in GFAP staining with MPTP (30 mg/kg). A main effect increase in GFAP was observed for PM (200 mg/kg), but not for CPF (50 mg/kg) or PM+CPF. Insecticides, alone or combined, did not alter MPTP-induced toxicity. . However, the absence of the PM-induced increase in GFAP staining following combined insecticide treatment suggests a neuroprotective effect. The next set of experiments in this dissertation looked at the effect of Mn on MPTP-induced neurotoxicity in the nigrostriatal and mesocortical dopaminergic pathways of the C57BL/6 mouse. Inductively Coupled Plasma atomic emission spectrometry revealed striatal Mn levels were significantly increased with multiple dose 100, 50, and 25 mg/kg MnCl2. Administration of Mn (MnCl2 s.c., Days 1, 4, & 7) in the MPTP (20 mg/kg i.p., Day 8) treated C57BL/6 mouse revealed Mn and MPTP interactions for locomotor activity, grip strength, and repeated measures of learning. Mn attenuated the effect of MPTP on striatal DOPAC, and facilitated the effect of MPTP on cortical DA and DOPAC. Mn also attenuated the MPTP induced decrease in cortical DAT. While these data support the notion that insecticides can produce tissue damage in the nigrostriatal pathway, in this case, these insecticide induced changes were not found to be strong enough to facilitate PD-like tissue damage. While Mn did not always facilitate MPTP neurotoxicity in the mesocortical and nigrostriatal dopaminergic pathways, these results demonstrate Mn and MPTP can interact in a complex way to alter dopaminergic function as well as motor and cognitive behavior. Differences in brain uptake mechanisms and metabolism of Mn and MPTP, could explain why combined administration of Mn and MPTP differentially affect dopaminergic activity in the nigrostriatal and mesocortical pathways. / Ph. D.

Parkinson's disease (PD) is a debilitating motor disorder that primarily afflicts older individuals (> 50yrs). Although its cause is unknown, many factors are thought to contribute to the disease. There is growing epidemiological evidence supporting a link between pesticide exposure and PD. The present immunohistochemical study was undertaken to characterize the role of insecticide exposure in the etiology of idiopathic PD. The insecticides selected for study were the pyrethroid permethrin (PE) and the organophosphate chlorpyrifos (CP), both of which possess properties that could damage or disrupt the nigrostriatal pathway, which is the principal neurodegenerative target in PD. The present study examined possible alteration of the amount of dopamine re-uptake transporter protein (DAT), within the striatum of the C57BL/6 mouse, using DAT antibodies, following low (0.8, 1.5 & 3.0 mg/kg) and high (200 mg/kg) doses of PE, respectively. Possible nigrostriatal terminal degeneration was examined using antibodies to tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine synthesis, following treatment with 50 mg/kg of CP alone or in combination with the high dose of PE. For both the high dose of PE alone and for the combined PE/CP treatment, glial fibrillary acidic protein (GFAP) antibodies were used to examine the possibility of non-degenerative tissue injury. Groups of matched treated/vehicle-control mice received three IP injections of the insecticide/dose of interest over a 2-week period. Counts of immunoreactive (IR) neuropil in the dorsolateral striatum were made from four pre-selected fields per striatal tissue section. Counts were compared between matched sections, processed on the same slide, from a treated mouse and its vehicle control. A mean difference score, across slides, for each treated/vehicle control pair was determined. All low dose PE groups showed a trend of decreased DAT IR neuropil, but only the 3.0mg/kg group showed a statistically significant reduction (p<.0078). The 200 mg/kg PE group showed a trend toward reduced TH IR neuropil that was not statistically significant, but a significant increase in GFAP IR (p = .048) was observed. No significant change in TH IR neuropil was observed for CP (50mg/kg) alone. A significant increase was observed for GFAP IR neuropil for the PE/CP (200/50 mg/kg) combination dose (p = .033). The combined insecticide treatment failed, however, to produce a significant change in TH IR within the striatum, compared to vehicle controls. These data suggest that the significant increases in GFAP IR neuropil, in the striatum, reflect some form of tissue insult, following exposure to a high dose of PE, or PE/CP in combination, that is insufficient to induce degeneration of dopaminergic terminals within the temporal interval investigated. Although such damage may be sufficient to account for previously reported decreases in maximal dopamine uptake observed with high doses of these compounds, the DAT IR data appear to indicate that this damage is unlikely to be a change in the amount of DAT in these high dose conditions. The decreases in striatal DAT IR neuropil observed for low doses of PE suggest an alteration in the normal integrity of the nigrostriatal pathway and in the route by which environmental toxins may enter dopaminergic neurons. / Master of Science

Inhibited immune responses have been observed following occupational, inadvertent, or therapeutic exposure to chemically diverse xenobiotics. In the present studies, preliminary data were generated showing limited but significant systemic immunotoxicity following low-level topical exposure to the pyrethroid insecticide, permethrin (formerly not considered an immunotoxicant). Permethrin was applied to the shaved dorsal interscapular region of C57Bl/6N mice at doses of 0.5, 1.5, or 5.0 μl/day. The highest of these doses was approximately equal to 215 μg/kg/day, which is about seven times the estimated daily human exposure in individuals wearing permethrin treated clothing for insect protection. Mice were thus exposed to permethrin daily for 10 or 30 consecutive days, or every other day for 7 or 14 exposures. Body weight was not affected by the treatment. However thymic weight was decreased and splenic weight increased 2 days after termination of the topical exposure. Histopathology of immune organs showed no significant changes. Splenic macrophages showed significantly depressed chemiluminescent responses up to 10 days following termination of exposure, but macrophage phagocytic activity was not affected. Cell surface markers of thymocytes, splenocytes and bone marrow cells were not affected. Antibody production as shown by plaque forming cell (PFC) assay decreased significantly at 10 days after dosing termination. Taken together, these data indicate that low-level topical permethrin exposure may produce systemic immunotoxicity. / Master of Science

"The goals of this study were (1) to evaluate the impacts of pesticides used for mosquito control on drinking water and (2) to investigate the removal of permethrin from water using activated carbon. A review of current literature on pesticide usage, toxicity, occurrence in the environment, and treatment techniques to remove pesticides from drinking water was conducted. The focus of the literature review was on pesticides used for mosquito control. Permethrin is a synthetic pyrethroid insecticide used extensively in the United States (US) for mosquito control and in agriculture, with approximately 2 million pounds applied each year. Permethrin was selected for investigation based on its widespread use in the US, its inclusion on the Contaminant Candidate List 3 (CCL3), its health hazards, and the lack of previous research on the removal of permethrin from drinking water. The removal of permethrin from water using powdered activated carbon (PAC) was investigated. Equilibrium adsorption experiments to assess removal of cis-, trans-, and total permethrin were conducted using two types of PAC (WPH 650 and WPH 1000). Initial total permethrin concentrations ranged from 2.0 to 4.6 ug/L. PAC doses ranged from 0.0 to 10 mg/L. Results showed that PAC addition is an effective method for removing permethrin from water. Total permethrin concentrations were reduced by 38% with 0.05 mg/L of PAC WPH 650, and reduced to below the detection limit with 3 mg/L of PAC WPH 650. Total permethrin concentrations were reduced by 35% with 0.05 mg/L of PAC WPH 1000 and by 83% with 5 mg/L of PAC WPH 1000. Results for cis- and trans- permethrin were similar. The Freundlich isotherm model provided appropriate fits to the data with an R-squared value of 0.91 for both WPH 650 and WPH 1000."

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniversitet, 2009. / Härtill 3 uppsatser.

The immunotoxic effects of multiple pesticide exposure were evaluated. C57BL/6 mouse thymocytes were exposed to lindane, malathion, and permethrin, either separately or in mixtures of two pesticides, in concentrations ranging from 37.5 uM to 1mM. These exposures caused both apoptotic and necrotic cell death in thymocytes as evaluated by 7-aminoactinomycin-D, Annexin-V/PI, and lactate dehydrogenase release assays. When cells were exposed to lindane+malathion, or lindane+permethrin, a significantly greater-than-additive cytotoxicity was observed. The pesticide exposure caused DNA ladder formation with increased laddering in mixtures. Further, the effect of these pesticides on thymocyte oxidative stress was investigated. Thymocytes treated with any of these pesticides generated superoxide and H2O2. The lindane + malathion caused more-than-additive increase in superoxide production compared to single treatments of these pesticides. However, the effect of the lindane + permethrin was not significantly different from individual components of this mixture. The effects of pesticides on antioxidant enzymes were also investigated and only mixtures were found to have significant effects. Alteration in transcription factor NFkB level was measured as an indicator of oxidative stress in thymocytes following 12 h pesticide exposure, in vitro. Only lindane + malathion was found to increase the protein level. Furthermore, the effects of pesticides and their mixtures on immune functions of mice were studied in vivo. Animals (8-12 week old, male mice) were randomly divided into groups of six and injected intraperitoneally with three different doses (one-half, one-third, one-fourth, or one-eight of LD50) of individual pesticides. Exposure to individual pesticides did not alter the thymus/body or spleen/body weight ratios, thymic or splenic cell counts, or CD4/CD8 or CD45/CD90 ratios. However, anti-sRBC plaque forming cell (PFC) counts were significantly lowered with all treatments. Two other groups of animals were injected with lindane + malathion or lindane + permethrin at one-third of the LD50 of each pesticide. Exposure to pesticide mixtures did not alter the CD4/CD8 or CD45/CD90 ratios. However, the thymus/ and spleen/body weight ratios, thymic and splenic cell counts, and PFC counts were significantly lowered. These data indicate that lindane, malathion, and permethrin are immunotoxic and their mixtures can cause higher toxicity compared to individual exposures. In addition, these data support the hypothesis that oxidative stress were induced in thymocytes by exposure to these pesticides in vitro. / Ph. D.

The present study examined adverse effects of sunlight exposure (mimicked by intradermal cis-urocanic acid, cUCA) on local and systemic immune responses, with or without co-exposure to the immunotoxic insecticide permethrin. A single exposure to cUCA caused diminished splenic macrophage phagocytosis that was persistent up to 30 days post-exposure. Five-day exposure to cUCA subtly increased splenocyte proliferation in response to the T cell mitogen Concanavalin A. Four-week exposure to cUCA caused increased splenic lymphocyte cellularity, thymic hypocellularity, and enhanced hydrogen peroxide production by splenic leukocytes. Single exposure to topical permethrin resulted in decreased thymic and splenic weight and cellularity, and inhibited antibody production by splenic B cells. cUCA worsened the negative effect of permethrin on both thymic weight and cellularity, and depressed splenocyte blastogenesis, hydrogen peroxide production, and antibody production. Five-day exposure to either cUCA or permethrin also caused persistent decreased contact hypersensitivity responses, an effect that became more than additive when the chemicals were administered concurrently. Defects in antigen processing and presentation by cutaneous Langerhans cells were evaluated as possible contributing mechanisms to the cutaneous immunosuppression, using mice with deleted genes. Vehicle-exposed IFNg knockout mice displayed approximately a 22.1% depression in the ear swelling response as compared to control C57BL/6N mice, suggesting that this cytokine may be required for mounting a control-level hypersensitivity response. Ear swelling in cUCA-exposed IFNg knockout mice displayed a 21.4% depressed response as compared to cUCA-exposed wild-type C57BL/6N mice, again suggesting that IFNg is an important cytokine in the contact hypersensitivity (CH) response. TNFaR knockout mice exposed to cUCA displayed 33.9% greater ear swelling than cUCA-exposed wild-type C57BL/6N mice, suggesting that increased TNFa may be involved in inhibited CH by cUCA. TNFaR knockout mice exposed to permethrin displayed 33.9% greater ear swelling than permethrin-exposed C57BL/6N mice, suggesting that increased TNFa may also be involved in inhibited CH by permethrin. C57BL/6N mice exposed to cUCA + permethrin displayed severe reduction of the CH response to 8.7% of the control level. IFNg knockout mice exposed to permethrin + cUCA showed essentially identical depression of the CH response as IFNg knockout mice exposed to either permethrin or cUCA alone. These results suggest that IFNg is required for the greater than additive immunotoxic effect that occurred when these two agents were co-administered. TNFaR knockout mice exposed to cUCA + permethrin displayed 8.7 fold greater ear swelling than similarly exposed C57BL/6N mice, again suggesting that increased TNFa is involved in inhibited CH by both cUCA and permethrin. / Ph. D.

Submitted by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2018-09-26T15:37:44Z No. of bitstreams: 1 EDUARDO MASSOCO RIOS.pdf: 697758 bytes, checksum: f2a0abeaa3dca510f53cb43dd3b46313 (MD5) / Approved for entry into archive by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2018-09-26T15:38:24Z (GMT) No. of bitstreams: 1 EDUARDO MASSOCO RIOS.pdf: 697758 bytes, checksum: f2a0abeaa3dca510f53cb43dd3b46313 (MD5) / Made available in DSpace on 2018-09-26T15:38:24Z (GMT). No. of bitstreams: 1 EDUARDO MASSOCO RIOS.pdf: 697758 bytes, checksum: f2a0abeaa3dca510f53cb43dd3b46313 (MD5) Previous issue date: 2017-08-19 / Pelo uso crescente de inseticidas em residências há uma crescente preocupação com os efeitos na saúde da população pela utilização doméstica desses produtos. O consumidor, que na maioria das vezes, desconhece as propriedades tóxicas dos componentes dessas formulações como se fossem inócuos, porém na realidade foram encontrados sintomas como redução da performance intelectual, distúrbios visuais e auditivos, polineuropatia sensitivo-motora e alterações neurovegetativas, e foram encontradas evidências laboratoriais de distúrbios da imunidade celular e humoral pelo uso excessivo desses produtos. A piretrina, é um componente ativo extraído das flores de crisântemos e tem sido muito utilizada há mais de dois séculos no controle de inúmeras espécies de insetos. No Brasil tem seu uso autorizado para aplicação foliar nas culturas de algodão, arroz, café, couve, couve-flor, milho, repolho, soja, tomate e trigo. Os efeitos da exposição crônica aos contaminantes ambientais surgem após um intervalo de tempo variável podendo resultar em eventos adversos sobre o sistema nervoso, respiratório, cardiovascular e reprodutivo. Este trabalho teve como objetivo avaliar a dispersão do spray de pesticida residencial e sua maior concentração de piretróides em domicílios urbanos. Para a avaliação da propagação dos pesticidas em ambientes fechados foi realizado um teste com fórmula comercial para identificar o alcance da distância e a quantificação da concentração dos mesmos em cada um dos pontos. Foram 24 jatos em 4 horas. Nos ensaios de recuperação obteve-se valores entre 80 e 104% para as concentrações 1,3 e 6 mg.L-1. Encontrou-se uma concentração de 2,32 mg.L-1 para a menor distância da lata de spray e para a maior distância (11,4 m) a quantidade de pesticida encontrada foi de 0,58 mg.L-1. Isso demonstra que ao usar o dispositivo próximo aos móveis, poderá acarretar um risco maior de contaminação humana por pesticidas. Assim, estima-se que o uso indiscriminado de inseticidas nos domicílios cause danos na saúde humana, constituindo-se em um potencial problema de Saúde Pública. / There is a growing concern about the effects on the population health by the domestic use of these products due to the increasing use of insecticides in homes. The consumer, who for the most part is unaware of the toxic properties of the components of these formulations as if they were innocuous, however, symptoms such as reduced intellectual performance, visual and auditory disorders, sensory-motor polyneuropathy and neurovegetative alterations were found, also a laboratory evidence of cellular and humoral immunity observed disorders due to excessive use of these products. Pyrethrin is an active component extracted from chrysanthemum flowers and has been widely used for over two centuries in controlling numerous insect species. In Brazil, it has authorized its use for foliar application in cotton, rice, coffee, kale, cauliflower, corn, cabbage, soybean, tomato and wheat crops. The chronic exposure effects to environmental contaminants arise after a variable time interval and may result in adverse events on the nervous, respiratory, cardiovascular and reproductive systems. This work aimed to evaluate the dispersion of the domestic pesticide spray and its higher concentration of pyrethroids in urban households. For evaluation the pesticides spread indoors, a commercial pesticide test was performed to identify the range of pesticides and the extent of pesticide concentration at each point. There were twenty-four (24) jets in four hours. In the recovery essays were obtained values between 80 and 104% for 1,3 and 6 mg.L-1 concentrations. It was found a 2,32 mg.L-1 for the shortest distance from the spray and for the longest distance (11,4m) the amount of pesticide was 0,58 mg.L-1. It points out that using devices next to the furniture, it may carry a greater risk of human contamination by pesticides. Therefore, it is estimated that the indiscriminate use of insecticides in households causes damage to human health, constituting a potential public health problem. / Por el uso creciente de insecticidas en residencias hay uma creciente preocupación com los efectos en la salud de la población por la utilización doméstica de estos produtos. El consumidor que en la mayoría de las veces desconoce las propiedades toxicas de los componentes de esas fórmulas como si fuesen inofensivos. Pero en realidad se encontraron síntomas como reducción del comportamiento intelectual, disturbios visuales y auditivos, polineuropatías sensitiva motora y alteración neurovegetativas y fueron encontradas evidencias científicas de disturbios de la inmunidad celular y multicelular por el uso excessivo de estos productos. La piretrina, en un componente activo extraído de las flores del crisantemo y viene siendo utilizado hace más de dos siglos en el control de innumerables especies de insectos. En Brasil tiene su uso autorizado para la aplicación sobre las plantaciones de algodón, arroz, café, col, coliflor, maíz, repollo, soja, tomate, y trigo. Los efectos de la exposición crónica de los contaminantes ambientales surgen después de un intervalo de tiempo variable, pudiendo resultar en eventos adversos sobre el sistema nervioso, respiratorio, cardiovascular y/o reproductivo. Este trabajo tuvo como objetivo evaluar las aspersiones del spray del pesticida residencial y su mayor concentración de piretroides en domicilios urbanos. Para la evaluación de la propagación de los pesticidas en ambientes cerrados, fue realizado pruebas con una fórmula comercial para identificar el alcance de la distancia y la cantidad de cocentración de los mismos en cada uno de los puntos. Fueron 24 aspersiones en 4 horas. En los ensayos se obtuvo valores entre 80 y 104 % para las concentraciones 1, 3 y 6 mg.L-1. Se ha encontrado una concentración de 2,32 mg.L-1 para la menor distancia de la lata de spray y para mayor distancia (11,4 m) la cantidad de pesticida encontrado fue de 0,58 mg.L-1. Esto demuesta que al usar el dispositivo cerca de los muebles, puede acarrear un riesgo mayor de contaminación humana por pesticida. Así se estima que el uso indiscriminado de insecticidas en los domicilios cause daños en la salud humana, convirtiéndose en un potencial problema de salud pública.

La perméthrine fait partie de la famille des pyréthrinoïdes qui sont abondamment utilisés en agriculture. Le but de cette étude était d'obtenir des données sur la cinétique des biomarqueurs d'exposition à la perméthrine en condition réelle d'exposition chez les travailleurs agricoles. Douze travailleurs (un applicateur, un superviseur et dix cueilleurs) exposés à la perméthrine dans le cadre de leur emploi ont été recrutés dans une ferme maraichère de la Montérégie (Québec). Ils ont fourni toutes leurs urines sur une période de trois jours suivant le début des travaux dans un champ traité. Les trois principaux métabolites de la perméthrine, l'acide cis-/trans-3-(2,2-dichlorovinyle)-2,2-diméthylecyclopropane carboxylique (cis-/trans-DCCA) et l'acide 3-phénoxybenzoïque (3-PBA) ont été analysés par chromatographie liquide à ultra-haute performance couplée à la spectrométrie de masse à temps de vol. Pour l'applicateur, une augmentation progressive des valeurs d'excrétion a été observée avec un pic unique atteint environ 30 h après le début de l'exposition d'une durée de 3,5 h suivi d'une élimination avec une demi-vie de 8 h. Pour le superviseur et l'un des cueilleurs, les profils d'excrétion de trans-DCCA et de 3-PBA étaient compatibles avec de multiples entrées dans la zone traitée pendant la période d'échantillonnage accompagné d'une élimination rapide entre les épisodes d'exposition.L'applicateur aurait été exposé indirectement par contact main-bouche, alors que les autres travailleurs auraient été exposés par la voie cutanée. Pour une surveillance biologique adéquate, nous recommandons de mesurer deux biomarqueurs de la perméthrine, soit le trans-DCCA et le 3-PBA et de prendre un minimum de trois échantillons urinaires, un avant et deux pendant ou suivant la période d'exposition. / Permethrin is a synthetic pyrethroid insecticide widely used in agriculture worldwide. This study aimed at obtaining data on the time courses of biomarkers of exposure to permethrin in agricultural workers following typical exposure conditions. Twelve workers (an applicator, a supervisor and ten harvesters) exposed to permethrin were recruited from a corn production farm in the Montérégie (Quebec). They provided all their urine voided over a period of three days following the onset of a spraying episode of permethrin or work in a treated area. Three major metabolites of permethrin, cis-/trans-3-(2,2-dichlorovinyl)-2,2-dimethylycyclopropane carboxylic acid (cis-/trans-DCCA) and 3-phenoxybenzoic acid (3-PBA) were analyzed by ultra-high performance liquid chromatography coupled to quadripole time-of-flight mass spectrometry (UHPLC/Q-TOF MS). For the applicator, a progressive rise in excretion values was observed with a single peak being reached about 30 h following the onset of the 3.5 h exposure and ensuing elimination with a half-life of 8 h. For the supervisor and one harvester excretion profiles of trans-DCCA and 3-PBA were more compatible with multiple entries in the treated area during the 3-day sampling period and rapid elimination between exposure episodes. The applicator would have been indirectly exposed by hand-to-mouth contact, while other workers would have been exposed by the dermal route. Time-dependent variability in excretion values of workers confirms the need for serial urine sampling of at least two biomarkers of exposure for routine biomonitoring, with minimally pre-exposure, end-of-shift sample the day of the onset of exposure and following morning void.