Pesticide exposure: the hormonal function of the female reproductive system disrupted?

Some pesticides may interfere with the female hormonal function, which may lead to negative effects on the reproductive system through disruption of the hormonal balance necessary for proper functioning. Previous studies primarily focused on interference with the estrogen and/or androgen receptor, but the hormonal function may be disrupted in many more ways through pesticide exposure. The aim of this review is to give an overview of the various ways in which pesticides may disrupt the hormonal function of the female reproductive system and in particular the ovarian cycle. Disruption can occur in all stages of hormonal regulation: 1. hormone synthesis; 2. hormone release and storage; 3. hormone transport and clearance; 4. hormone receptor recognition and binding; 5. hormone postreceptor activation; 6. the thyroid function; and 7. the central nervous system. These mechanisms are described for effects of pesticide exposure in vitro and on experimental animals in vivo. For the latter, potential effects of endocrine disrupting pesticides on the female reproductive system, i.e. modulation of hormone concentrations, ovarian cycle irregularities, and impaired fertility, are also reviewed. In epidemiological studies, exposure to pesticides has been associated with menstrual cycle disturbances, reduced fertility, prolonged time-to-pregnancy, spontaneous abortion, stillbirths, and developmental defects, which may or may not be due to disruption of the female hormonal function. Because pesticides comprise a large number of distinct substances with dissimilar structures and diverse toxicity, it is most likely that several of the above-mentioned mechanisms are involved in the pathophysiological pathways explaining the role of pesticide exposure in ovarian cycle disturbances, ultimately leading to fertility problems and other reproductive effects. In future research, information on the ways in which pesticides may disrupt the hormonal function as described in this review, can be used to generate specific hypotheses for studies on the effects of pesticides on the ovarian cycle, both in toxicological and epidemiological settings

Protocol for a systematic review and meta-analysis of human exposure to pesticide residues in honey and other bees' products

Background: The presence of pesticides in honey and related products is an increasing concern for consumers and producers, although there is lack of data on the current burden of exposure of the general human population through these products. We present a protocol for a systematic review and meta-analysis of contamination to insecticides, herbicides and fungicides of products from honeybees, and an estimation of how much the consumption of these products contributes to the ADI (Acceptable Daily Intake) of selected substances. Objectives: We aim to systematically review and meta-analyse studies on the contamination to plant protection products in honey, royal jelly, beeswax and propolis, applying the Navigation Guide and WHO-ILO systematic review methodology as an organizing framework. Data sources: We will search electronic academic databases for potentially relevant records from PubMed, TOXNET and EMBASE. We will include quantitative studies analysing the contamination from insecticides, herbicides and fungicides in honey, propolis, royal jelly and beeswax. In particular, we will evaluate the presence of the following substances and classes of pesticides: Glyphosate, Chlorpyrifos, pyrethroid and neonicotinoid pesticides, fungicides and acaricides. Study appraisal and synthesis methods: At least two authors will independently screen titles and abstracts at a first stage of review, and full texts at a second stage, of potentially eligible records against the eligibility criteria; data extraction of included studies will then be performed by at least two authors, in blind. At least two authors will assess risk of bias and the quality of evidence, using the most suited tools currently available. The data on prevalence of contaminated samples and concentration of pesticides in the products will be combined using meta-analysis: when more than three studies reporting the necessary measures to fit the models are available, meta-analysis will be performed separately by product and by exposure; otherwise, weighted descriptive analysis will be performed. We will report the results using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA)

Detect and re-assess impact of chemicals on health and environment during post-market evaluation

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Systematic review of comparative studies assessing the toxicity of pesticide active ingredients and their product formulations

Humans are exposed to complex chemical mixtures, such as pesticides. Although the need for the assessment of health and environmental hazards deriving from the interactions between various substances found in commercial pesticide formulations is becoming increasingly recognized, the approval of pesticide products is still mostly limited to determining the toxicity of the individual ingredients ignoring the possible combined effects in mixtures. The objective of this study was to systematically review the literature of in vitro and in vivo studies that simultaneously examine the toxicity of pesticide product formulations and their declared active ingredients to compare their toxicity to human health and to the environment. Two electronic databases were searched for studies that assessed the health effects of active pesticide ingredients and their product formulations. The literature search was performed with a combination of the following terms: "pesticide", "formulation", "commercial product", "commercial pesticide" and "health". After screening by predefined inclusion and exclusion criteria, quality and reliability assessment of eligible publications was conducted by use of the ToxRTool. Two investigators independently screened the identified publications and extracted results from eligible studies. Our search yielded 36 toxicity studies; 23 studies investigated herbicides, 15 examined insecticides and 4 focused on fungicides. Twenty-four studies reported increased toxicity of the product formulations versus their active ingredients, which, in most cases, were attributed to the presence of adjuvants in the formulations. A significant number (n = 10) of studies focused on the comparative testing of glyphosate and glyphosate-based herbicides, and six of them concluded that Roundup, the dominant product formulation of glyphosate, is more toxic than the active ingredient alone. We identified only 8 studies demonstrating reduced toxicity of product formulations in relation to the active ingredient that might be due to a potential antagonistic effect between the constituents. The results of this review demonstrate the inadequacy of current EU testing requirements for assessing the health hazards of pesticide product formulations based mainly on the evaluation of the individual ingredients and of at least one representative use and formulation. Ignoring the possible risks deriving from the interaction between the active and other ingredients of various commercial pesticide product formulations might result in the misinterpretation of its toxicological profile. At EU level efforts are currently made to address this issue. In this context, we recommend that all product formulations should be fully assessed during the authorization process.status: publishe

The acute effect of cigarette smoking on the high-sensitivity CRP and fibrinogen biomarkers in chronic obstructive pulmonary disease patients

Item does not contain fulltextAim: The evidence on the acute effects of smoking on biomarkers is limited. Our aim was to study the acute effect of smoking on disease-related biomarkers. Methods: The acute effect of smoking on serum high sensitivity CRP (hs-CRP) and plasma fibrinogen and its association with disease severity was studied by challenging 31 chronic obstructive pulmonary disease patients with cigarette smoking and repeatedly measuring these biomarkers before and after smoking. Results: Fibrinogen and hs-CRP increased directly after smoking by 9.4 mg/dl (95% CI: 4.2-14.5) and 0.13 mg/l (95% CI: 0.03-0.23), respectively. Fibrinogen levels remained elevated after 35 min, whereas hs-CRP normalized. Pearson's correlation coefficient between the hs-CRP change and chronic obstructive pulmonary disease severity was 0.25 (p = 0.06). Conclusion: Fibrinogen and hs-CRP increased directly after smoking in the chronic obstructive pulmonary disease patients. Their association with disease risk and/or progression remains to be demonstrated

Assessment of exposure of gas station attendants in Sri Lanka to benzene, toluene and xylenes

Exposure to benzene, toluene and p-, m-, o-xylene (BTX) was studied in 29 gas station attendants and 16 office workers in Sri Lanka. The aim of this study was to assess the exposure level and identify potential exposure mitigating measures. Pre- and post-shift samples of end-exhaled air were collected and analysed for BTX on a thermal desorption gas chromatography mass spectrometry system (TD-GC-MS). Urine was collected at the same timepoints and analysed for a metabolite of benzene, S-phenyl mercapturic acid (SPMA), using liquid chromatography-mass spectrometry (LC-MS). Environmental exposure was measured by personal air sampling and analysed by gas chromatography flame ionization detection (GC-FID). Median (range) breathing zone air concentrations were 609 (65.1-1960) μg/m3 for benzene and 746 (<5.0-2770) μg/m3 for toluene. Taking into account long working hours, 28% of the measured exposures exceeded the ACGIH threshold limit value (TLV) for an 8-h time-weighted average of 1.6 mg/m3 for benzene. Xylene isomers were not detected. End-exhaled air concentrations were significantly increased for gas station attendants compared to office workers (p < 0.005). The difference was 1-3-fold in pre-shift and 2-5-fold in post-shift samples. The increase from pre-to post-shift amounted to 5-15-fold (p < 0.005). Pre-shift BTX concentrations in end-exhaled air were higher in smokers compared to non-smokers (p < 0.01). Exposure due to self-reported fuel spills was related to enhanced exhaled BTX (p < 0.05). The same was found for sleeping at the location of the gas station between two work-shifts. Benzene in end-exhaled air was moderately associated with benzene in the breathing zone (r = 0.422; p < 0.001). Median creatinine-corrected S-phenyl mercapturic acid (SPMA) was similar in pre- and post-shift (2.40 and 3.02 μg/g) in gas station attendants but increased in office workers (from 0.55 to 1.07 μg/g). In conclusion, working as a gas station attendant leads to inhalation exposure and occasional skin exposure to BTX. Smoking was identified as the most important co-exposure. Besides taking preventive measure to reduce exposure, the reduction of working hours to 40 h per week is expected to decrease benzene levels below the current TLV.status: publishe

WHO/ILO work-related burden of disease and injury: Protocol for systematic reviews of occupational exposure to dusts and/or fibres and of the effect of occupational exposure to dusts and/or fibres on pneumoconiosis

BACKGROUND: The World Health Organization (WHO) and the International Labour Organization (ILO) are developing a joint methodology for estimating the national and global work-related burden of disease and injury (WHO/ILO joint methodology), with contributions from a large network of experts. In this paper, we present the protocol for two systematic reviews of parameters for estimating the number of deaths and disability-adjusted life years attributable to pneumoconiosis from occupational exposure to dusts and/or fibres, to inform the development of the WHO/ILO joint methodology. OBJECTIVES: We aim to systematically review studies on occupational exposure to dusts and/or fibres (Systematic Review 1) and systematically review and meta-analyse estimates of the effect of occupational exposure to dusts and/or fibres on pneumoconiosis (Systematic Review 2), applying the Navigation Guide systematic review methodology as an organizing framework. DATA SOURCES: Separately for Systematic Reviews 1 and 2, we will search electronic academic databases for potentially relevant records from published and unpublished studies, including Medline, EMBASE, Web of Science and CISDOC. We will also search electronic grey literature databases, Internet search engines and organizational websites; hand-search reference list of previous systematic reviews and included study records; and consult additional experts. STUDY ELIGIBILITY AND CRITERIA: We will include working-age (≥15 years) study participants in the formal and informal economy in any WHO and/or ILO Member State but exclude children (<15 years) and unpaid domestic workers. Eligible risk factors will be dusts and/or fibres from: (i) asbestos; (ii) silica; and/or (iii) coal (defined as pure coal dust and/or dust from coal mining). Included outcomes will be (i) asbestosis; (ii) silicosis; (iii) coal worker pneumoconiosis; and (iv) unspecified pneumoconiosis. For Systematic Review 1, we will include quantitative prevalence studies of occupational exposure to dusts and/or fibres (i.e. no versus any exposure) stratified by country, sex, age and industrial sector or occupation. For Systematic Review 2, we will include randomized controlled trials, cohort studies, case-control studies and other non-randomized intervention studies with an estimate of any occupational exposure to dusts and/or fibres on the prevalence of, incidence of or mortality due to pneumoconiosis, compared with the theoretical minimum risk exposure level of no exposure. STUDY APPRAISAL AND SYNTHESIS METHODS: At least two review authors will independently screen titles and abstracts against the eligibility criteria at a first stage and full texts of potentially eligible records at a second stage, followed by extraction of data from qualifying studies. At least two review authors will assess risk of bias and the quality of evidence, using the most suited tools currently available. For Systematic Review 2, if feasible, we will combine relative risks using meta-analysis. We will report results using the guidelines for accurate and transparent health estimates reporting (GATHER) for Systematic Review 1 and the preferred reporting items for systematic reviews and meta-analyses guidelines (PRISMA) for Systematic Review 2. PROSPERO REGISTRATION NUMBER: CRD42018084131.status: publishe

Diagnosis, monitoring and prevention of exposure-related non-communicable diseases in the living and working environment: DiMoPEx-project is designed to determine the impacts of environmental exposure on human health

The WHO has ranked environmental hazardous exposures in the living and working environment among the top risk factors for chronic disease mortality. Worldwide, about 40 million people die each year from noncommunicable diseases (NCDs) including cancer, diabetes, and chronic cardiovascular, neurological and lung diseases. The exposure to ambient pollution in the living and working environment is exacerbated by individual susceptibilities and lifestyle-driven factors to produce complex and complicated NCD etiologies. Research addressing the links between environmental exposure and disease prevalence is key for prevention of the pandemic increase in NCD morbidity and mortality. However, the long latency, the chronic course of some diseases and the necessity to address cumulative exposures over very long periods does mean that it is often difficult to identify causal environmental exposures. EU-funded COST Action DiMoPEx is developing new concepts for a better understanding of health-environment (including gene-environment) interactions in the etiology of NCDs. The overarching idea is to teach and train scientists and physicians to learn how to include efficient and valid exposure assessments in their research and in their clinical practice in current and future cooperative projects. DiMoPEx partners have identified some of the emerging research needs, which include the lack of evidence-based exposure data and the need for human-equivalent animal models mirroring human lifespan and low-dose cumulative exposures. Utilizing an interdisciplinary approach incorporating seven working groups, DiMoPEx will focus on aspects of air pollution with particulate matter including dust and fibers and on exposure to low doses of solvents and sensitizing agents. Biomarkers of early exposure and their associated effects as indicators of disease-derived information will be tested and standardized within individual projects. Risks arising from some NCDs, like pneumoconioses, cancers and allergies, are predictable and preventable. Consequently, preventative action could lead to decreasing disease morbidity and mortality for many of the NCDs that are of major public concern. DiMoPEx plans to catalyze and stimulate interaction of scientists with policy-makers in attacking these exposure-related diseases.status: publishe