The aim of this work is to prepare a proposal for the post-authorization monitoring (PAM) of veterinary medicinal products (VMP), in particular parasiticides. Such a monitoring might especially be useful for parasiticides identified as Persistence Bioaccumulation Toxicity (PBT) substances, i.e., chemicals that are toxic (T), persist in the environment (P) and bioaccumulate (B) in food chains and, thus, pose a hazard to ecosystems. Based on a literature search, issues to be considered when performing such a PAM are discussed (e.g., residue analysis, compartments to be included, selection of organisms and the duration of monitoring studies). The outcome of this discussion is that—and despite that there are huge challenges in detail (e.g., in terms of analytical chemistry or taxonomy)—the technical performance of such a PAM is not the main problem, since most of the chemical and biological methods to be used are well-known (partly even standardized) or could be adapted. However, it is very difficult to define in detail where and when a monitoring should be performed. The main problem is to link exposure to effects of a certain parasiticide in a way that any impact can directly be related to the use of this parasiticide. Therefore, a “Targeted Environmental Monitoring” (TEM) is proposed, which is essentially a combination between a field study and a PAM. Full article

The widespread use of pesticides in agriculture represents a threat to the human populations exposed to them. In this cross-sectional study, the hematological and biochemical parameters, plasma cholinesterase (PChE) activity, oxidative stress, genotoxicity, and NAD(P)H: quinone oxidoreductase 1 (NQO1) C609T polymorphism were measured in 100 greenhouse workers occupationally exposed to pesticide mixture and 104 normal healthy controls. There was a decrease in erythrocytes (5.45%, p = 0.026) and hemoglobin (3.26%, p = 0.025), and an increase in mean corpuscular hemoglobin (3.54%, p = 0.013) in the exposed workers. Sprayers showed a reduction in PChE (23%) and GSH (50%) levels, and an increase in lipid peroxidation (LPO) (55%), protein carbonyl (145%), Superoxide dismutase activity (61%), and total antioxidant capacity (35%) (p < 0.001 for all parameters but LPO: p = 0.009). Genotoxicity parameters were significantly high in the exposed cases (for all parameters: p < 0.001 but tail length: p = 0.002). There was a significant correlation between oxidative stress and genotoxicity parameters, and also between these biomarkers and PChE activity. The NQO1 C609T polymorphism was not significantly associated with studied biomarkers. The findings indicate that occupational exposure to a mixture of pesticides can induce hematotoxicity, oxidative stress, and genotoxicity in greenhouse workers. Full article

Toxicants, such as herbicides, have been hypothesized to affect sperm parameters. The most common method of exposure to herbicides is through spraying or diet. The aim of the present study was to investigate the effect of direct exposure of sperm to 1 mg/L of the herbicide Roundup on sperm motility and mitochondrial integrity. Sperm samples from 66 healthy men who were seeking semen analysis were investigated after written informed consent was taken. Semen analysis was performed according to the World Health Organization guidelines (WHO, 2010). Mitochondrial integrity was assessed through mitochondrial staining using a mitochondria-specific dye, which is exclusively incorporated into functionally active mitochondria. A quantity of 1 mg/L of Roundup was found to exert a deleterious effect on sperm’s progressive motility, after 1 h of incubation (mean difference between treated and control samples = 11.2%) in comparison with the effect after three hours of incubation (mean difference = 6.33%, p < 0.05), while the relative incorporation of the mitochondrial dye in mitochondria of the mid-piece region of Roundup-treated spermatozoa was significantly reduced compared to relative controls at the first hour of incubation, indicating mitochondrial dysfunction by Roundup. Our results indicate that the direct exposure of semen samples to the active constituent of the herbicide Roundup at the relatively low concentration of 1 mg/L has adverse effects on sperm motility, and this may be related to the observed reduction in mitochondrial staining. Full article

Chemical pesticides are widely used in Cameroon for agricultural production. In 2015, more than 600 pesticide products were approved for use in various foodstuffs. Much misuse of these chemicals by farmers has been documented in rural and urban settings. This pilot study aims to contribute to the improvement of the health of the population and the environmental preservation by identifying pesticide-poisoning cases, the most incriminated products and critical risk factors of exposure. Questionnaires were administered to pesticide vendors, farmers and health personnel, and observations made on farmers’ practices at their work places. From July to September 2016, 24 villages from five sites, representing the most important agricultural production areas of the five agro-ecological zones of Cameroon, were visited. In total, 519 people were interviewed: 412 farmers, 69 pesticide vendors and 38 health personnel. A total of 180 pesticide formulations out of 610 registered in 2015 were said to be used by farmers. In the 38 health centers visited, 56 cases of pesticide poisonings and intoxications were reported between 2011 and 2016. Paraquat-, glyphosate-, cypermethrin- and metalaxyl-formulated pesticides were the most incriminated. In total, 78% of poisoning cases were accidental, 12% suicide attempts, 4% criminal. Entry of pesticide products from neighboring countries needs to be better regulated, and the quality of pesticides sold on the market should be monitored periodically. Empty pesticide containers should be recuperated from smallholder farmers. Authorities should set up a harmonized pesticide-poisoning management procedure, and create a toxico-vigilance system for surveillance cases and preventive actions. Full article

The objective of the study was to describe self-reported health symptoms, the use of personal protective gear and clothing and poor safety procedures when applying pesticides among farm workers. A total of 128 adult farm workers were interviewed using a structured questionnaire during the farming season. The commonly used pesticides included profenofos, mancozeb, chlorpyrifos, cypermethrin, deltamethrin, permethrin, lambda-cyhalothrin, endosulfan and carbosulfan. The majority (>90%) of farm workers used no personal protective clothing while handling pesticides. More than one-third of farm workers ate and drank without washing their hands following pesticide handling, while a smaller number smoked or chewed gum. Wearing special boots during pesticide application was found to reduce the risk of skin rash (OR = 0.2, 95% CI: 0.06–0.66), whereas smoking when applying pesticides increased the risk of chest pain occurrence (OR = 4.0, 95% CI: 1.14–15.43), as well as forgetfulness (OR = 4.0, 95% CI: 1.30–14.02). Chewing gum and eating when applying pesticides was associated with diarrhoea (OR = 11.0, 95% CI: 1.80–6.84 and OR = 7.0, 95% CI: 1.27–3.67 respectively). The increased self-reported prevalence of post-exposure adverse health effects among farm workers was associated with poor use of personal protective clothing and poor safety practices during pesticide use and handling. These data indicate the need for improved availability and use of protective equipment, and training in crop and pest management practices to prevent risky behavioursand for safer and sustainable vegetable production. Full article

The Albemarle-Pamlico Estuarine System (APES) is the second largest estuarine system within the mainland of the United States and is estimated to have lost about half of its submerged aquatic vegetation (SAV) over the past several decades. The issue of herbicide runoff and subsequent toxic effects to SAV is important because of the extensive agricultural production that occurs in the APES region. The aim of this study was to conduct a retrospective analysis of herbicide influx to waters of the APES region during the time period of documented SAV declines and to compare the measured concentrations to SAV toxicity thresholds and changes in agricultural land use. Surface water grab samples were collected at 26 sites in the APES region during May through July 2000. The most consistently measured herbicides were alachlor, atrazine, and metolachlor with geometric mean concentrations ranging from 29 to 2463 ng/L for alachlor, 14 to 7171 ng/L for atrazine, and 17 to 5866 ng/L for metolachlor. Concentrations of alachlor, atrazine, and metolachlor measured in water samples from the APES region in 2000 exceeded several of the established benchmarks, standards, or guidelines for protection of aquatic plants. Although this evaluation was of point-in-time herbicide samples (year 2000) and not analyzed for all possible herbicides used at the time, they were taken during the period of SAV declines, reveal the plausibility of exposure risk to SAV, and suggest that herbicide runoff should be studied along with other variables that influence SAV growth and distribution in future studies. Full article

Occupational exposure to pesticides in agricultural applications may cause acute and long-term health effects to farmers, and thus research on factors that reduce exposure is useful. However, studies on the relevance and effectiveness of training are limited. The association of previous training in the form of intensive seminars relating to pesticide use (e.g., use of spraying equipment, application parameters, use of personal protective equipment, risks to human health and the environment) with farmers’ knowledge and behavior in pesticide use was studied via the self-reporting method in a purposive sample of 82 trained and non-trained farmers. Most trained farmers showed higher levels of knowledge of pesticide use, higher levels of beliefs in pesticide hazard control, and higher levels of safety behavior than non-trained farmers. Knowledge of pesticide use and beliefs regarding pesticide hazard control were significantly correlated with safety behavior in both groups of farmers. Concerning farmers’ beliefs regarding pesticide hazard control, trained farmers were more likely to think that safety precautions work very well and less likely to feel they had little control over avoiding pesticide hazards. Overall, previous training was associated with increased levels of farmers’ knowledge of pesticides and beliefs about pesticide hazard control, was accompanied by elevated safety behavior in farmers, and thus was connected with lower occupational exposure to pesticides. Interventions that facilitate knowledge and compliance with safety behaviors should become a priority for decreasing exposure to pesticides among farmers. Full article

Urinary naphthol is an established human biomarker used for assessing both occupational and environmental exposure. However, 1-naphthol is a metabolite of the insecticide carbaryl while both the 1- and 2-isomers are metabolites of naphthalene. Thus, urinary 1-naphthol levels will reflect combined exposure to both substances, particularly at environmental levels. The interpretation of biomarkers is aided by knowledge of levels following well-characterised exposure scenarios. This study reports urinary 1-naphthol levels in five volunteers administered an oral dose of carbaryl at the acceptable daily intake (ADI, 0.008 mg/kg). The elimination half-life was 3.6 h and the mean 1-naphthol level in 24 h total urine collections, normalised for a 70 kg individual, was 37.4 µmol/mol creatinine (range 21.3–84.3). Peak levels in spot-urine samples were around 200 µmol/mol creatinine. For comparison, 327 post-shift urine samples obtained from 90 individual workers exposed occupationally to naphthalene had 1-naphthol levels from below the limit of detection (<LoD) to 1027 µmol/mol creatinine (median = 4.2, mean = 27.2). The 2-naphthol levels ranged from <LoD to 153 µmol/mol creatinine (median = 4.0, mean = 8.1). Background ranges have been reported for urine naphthols in several populations, with upper limits between 10 and 20 µmol/mol creatinine. The data reported here suggest that environmental exposure to carbaryl and naphthalene in these populations is well controlled. Full article

The indiscriminate use of pesticide is a treat to non-target organisms. This study evaluates the haematological and biochemical changes induced by inhalation of local Nigerian dichlorvos insecticide on rats. The rats were randomly assigned to a control group which received only food and water and a test group which, in addition to food and water, was exposed to the pesticide for a period of 4 h daily for 28 days, after which exposure was discontinued for seven days. Five animals were sacrificed from each group on days 1, 7, 14, 21, 28 and 35, and blood was collected by cardiac puncture for haematological, biochemical and antioxidant analysis. Results obtained showed lowered values of red blood cell count (RBC), packed cell volume (PCV), haemoglobin, mean cell haemoglobin (MCH) and mean cell haemoglobin concentration (MCHC) (p < 0.05) with increased white blood cell count (WBC) and platelet counts after day 14 when compared to the control group. Liver enzymes aspartate amino transaminase (AST) and alanine amino transaminase (ALT) were higher in the exposed rats compared to the control group (p < 0.05). Urea and creatinine concentrations increased significantly after day 1 and at day 28, while superoxide dismutase (SOD), gluthathione (GSH) and catalase (CAT) activity increased significantly compared to the control after day 1, day 14 and day 21, respectively. The RBC, PCV and haemoglobin values of all exposed rats were restored to normal following withdrawal of the pesticide, though AST, ALT, urea, creatinine and, glutathione values remained significantly high compared to the control. Inhalation of the local insecticide is toxic to the blood, liver and kidney of laboratory rats and may be deleterious to human health following long-term exposure. Full article

The study aimed to assess the association of long-term pesticide exposure (≥5 years) with hematological, serum biochemical parameters and acetylcholinesterase activity in farm workers. These pesticides included organophosphorus pesticides, carbamates, pyrethroids, dithiocarbamates, and other pesticides such as endosulfan. Applying a cross-sectional study design, 69 females from a pesticide-exposed farm population and 30 females from a district not using pesticides (reference group) were studied. The mean red cell corpuscular volume and hematocrit values were significantly lower (74.7 ± 9.1 fl; 95% CI 72.5–76.9 and 32.0% ± 4.6%; 95% CI 30.9–33.1, respectively) in the exposed compared to the reference group, whereas mean corpuscular hemoglobin concentration and platelets were significantly higher (37.4 ± 3.8 g/dL; 95% CI 36.5–38.3 and 374.1 ± 95.3/L; 95% CI 351.2–396.9, respectively) in the exposed compared to the reference group. Mean serum glutamic oxaloacetate transaminase (20.7 ± 8.9 U/L; 95% CI 18.5–22.9) and creatinine (83.9 ± 6.6 μmol/L; 95% CI 82.3–85.5) were significantly higher in the exposed compared to the reference group. A higher mean esterase activity (AChE 0.6 ± 0.2 mM/min/mg protein; 95% CI 0.56–0.7; BChE 0.9 ± 0.4 mM/min/mg protein; 95% CI 0.9–1.1) was noted in the exposed group. Regression models suggest that occupational exposure (p < 0.001) could be a predictor of esterase (AChE and BChE) activity and biochemical changes (β = 0.4, 95% CI: 0.3–0.5; β = 0.7, 95% CI: 0.6–0.9, respectively). Long-term pesticide exposure affects the hemato-biochemical and esterase responses, establishing the need for further studies. Full article

Penconazole is a widely used fungicide in the UK; however, to date, there have been no peer-reviewed publications reporting human metabolism, excretion or biological monitoring data. The objectives of this study were to i) develop a robust analytical method, ii) determine biomarker levels in volunteers exposed to penconazole, and, finally, to iii) measure the metabolites in samples collected as part of a large investigation of rural residents’ exposure. An LC-MS/MS method was developed for penconazole and two oxidative metabolites. Three volunteers received a single oral dose of 0.03 mg/kg body weight and timed urine samples were collected and analysed. The volunteer study demonstrated that both penconazole-OH and penconazole-COOH are excreted in humans following an oral dose and are viable biomarkers. Excretion is rapid with a half-life of less than four hours. Mean recovery of the administered dose was 47% (range 33%–54%) in urine treated with glucuronidase to hydrolyse any conjugates. The results from the residents’ study showed that levels of penconazole-COOH in this population were low with >80% below the limit of detection. Future sampling strategies that include both end of exposure and next day urine samples, as well as contextual data about the route and time of exposure, are recommended. Full article

Between 2007 and 2013, there were 685 events with evidence of a relationship between pesticide exposure and acute illness/injury among persons less than 18 years old in North Carolina (United States). Median age of children affected was 4.3 years (range: 0.2–17.9). Distribution by gender was similar across all age groups. One fatality and four high severity events were observed. The greatest proportion (42%) of events had ocular exposures, followed by dermal (25%) and inhalation (18%) exposures. When more than one route of exposure occurred, dermal and ocular routes were the most common (46%). Almost all events took place indoors and 32 events involved contact with pets. Insecticides (53%) and insect repellants (31%) were the most frequent agents contributing to these events. Manual application of pesticides contributed to the greatest number of events (25%), while application through a pressurized can and use of a trigger pump were involved in 21% and 15% of events, respectively. Additional contributors were due to inappropriate storage of pesticides and improper use of the pesticide. These contributing factors can be removed or minimized if pesticides are stored outside the residence or out of the reach of children and pets, and adequate ventilation is ensured whenever pesticides are applied. Full article

Hair is a non-invasive biological material useful in the biomonitoring of trace elements because it is a vehicle for substance excretion from the body, and it permits evaluating long-term metal exposure. Here, hair from an animal model of neurodegeneration, induced by early life permethrin treatment from the sixth to 21th day of life, has been analyzed with the aim to assess if metal and microelement content could be used as biomarkers. A hair trace element assay was performed by the ICP-MS technique in six- and 12-month-old rats. A significant increase of As, Mg, S and Zn was measured in the permethrin-treated group at 12 months compared to six months, while Si and Cu/Zn were decreased. K, Cu/Zn and S were increased in the treated group compared to age-matched controls at six and 12 months, respectively. Cr significantly decreased in the treated group at 12 months. PCA analysis showed both a best difference between treated and age-matched control groups at six months. The present findings support the evidence that the Cu/Zn ratio and K, measured at six months, are the best biomarkers for neurodegeneration. This study supports the use of hair analysis to identify biomarkers of neurodegeneration induced by early life permethrin pesticide exposure. Full article

Synthetic pesticides are extensively used in agriculture to control harmful pests and prevent crop yield losses or product damage. Because of high biological activity and, in certain cases, long persistence in the environment, pesticides may cause undesirable effects to human health and to the environment. Farmers are routinely exposed to high levels of pesticides, usually much greater than those of consumers. Farmers’ exposure mainly occurs during the preparation and application of the pesticide spray solutions and during the cleaning-up of spraying equipment. Farmers who mix, load, and spray pesticides can be exposed to these chemicals due to spills and splashes, direct spray contact as a result of faulty or missing protective equipment, or even drift. However, farmers can be also exposed to pesticides even when performing activities not directly related to pesticide use. Farmers who perform manual labor in areas treated with pesticides can face major exposure from direct spray, drift from neighboring fields, or by contact with pesticide residues on the crop or soil. This kind of exposure is often underestimated. The dermal and inhalation routes of entry are typically the most common routes of farmers’ exposure to pesticides. Dermal exposure during usual pesticide handling takes place in body areas that remain uncovered by protective clothing, such as the face and the hands. Farmers’ exposure to pesticides can be reduced through less use of pesticides and through the correct use of the appropriate type of personal protective equipment in all stages of pesticide handling. Full article

Glyphosate is the most commonly-used herbicide in the world. The present review summarizes the discovery, prevalence, chemical and physical properties, mode of action and effects in plants, glyphosate resistance and the environmental fate of glyphosate. Numerous studies are reviewed that demonstrate that glyphosate may run off of fields where it is applied, while other studies provide evidence that plant roots can take up glyphosate. Non-target vegetation may be exposed to glyphosate in the root-zone, where it has the potential to remove aqueous glyphosate from the system. Further study on the effects of root-zone glyphosate on non-target vegetation is required to develop best management practices for land managers seeking to ameliorate the effects of root-zone glyphosate exposure. Full article

Endocrine disrupting chemicals (EDC) are exogenous agents that alter endogenous hormone signaling pathways. These chemicals target the neuroendocrine system which is composed of organs throughout the body that work alongside the central nervous system to regulate biological processes. Of primary importance is the hypothalamic-pituitary-gonadal (HPG) axis which is vital for maintaining proper reproductive function. Atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine) is a pre-emergent herbicide used to prevent the growth of weeds on various crops. This herbicide is reported to widely contaminate potable water supplies everywhere it is applied. As such, the European Union banned the use of atrazine in 2004. Currently the United States Environmental Protection Agency regulates atrazine at 3 parts per billion (ppb; μg/L) in drinking water, while the World Health Organization recently changed their drinking water guideline to 100 ppb. Atrazine is implicated to be an EDC that alters reproductive dysfunction by targeting the HPG axis. However, questions remain as to the human health risks associated with atrazine exposure with studies reporting mixed results on the ability of atrazine to alter the HPG axis. In this review, the current findings for atrazine’s effects on the HPG axis are examined in mammalian, anuran, and fish models and in epidemiological studies. Full article

Haloxyfop-p-methyl ester (HPME) ((R)-2-{4-[3-chloro-5-(trifluoromethyl)-2-pyridyloxy]phenoxy}propionic acid), is a selective aryloxyphenoxypropionate (AOPP) herbicide. It exerts phytotoxicity through inhibition of lipid metabolism and induction of oxidative stress in susceptible plants. This study investigated the toxicological potentials of HPME in rats. Twenty-four male Wistar rats (170–210 g) were randomized into four groups (I–IV). Group I (control) received 1 mL of distilled water, while animals in Groups II, III and IV received 6.75, 13.5 and 27 mg/kg body weight HPME, respectively, for 21 days. There was a significant (p < 0.05) increase in renal and hepatic function biomarkers (urea, creatinine, total bilirubin, ALP, ALT, AST) in the plasma of treated animals compared to control. Levels of testicular antioxidants, ascorbic acid and glutathione, and activities of glutathione-S-transferase, superoxide dismutase and catalase were reduced significantly after 21 days of HPME administration in a dose-dependent manner. The testicular malondialdehyde level increased significantly in the HPME-treated rats relative to the control. A significant decrease in testicular lactate dehydrogenase, acid phosphatase and γ-glutamyl transferase was also observed in HPME-treated animals. Testicular histology revealed severe interstitial edema and sections of seminiferous tubules with necrotic and eroded germinal epithelium in the HPME-treated rats. Overall, data from this study suggest that HPME altered hepatic and renal function and induced oxidative stress and morphological changes in the testis of rats. Full article