Exposure to the Widely Used Fungicide Mancozeb Causes Thyroid Hormone Disruption in Rat Dams but No Behavioral Effects in the Offspring

Axelstad, Marta; Boberg, Julie; Nellemann, Christine; Kiersgaard, Maria Kristina; Jacobsen, Peter; Christiansen, Sofie; Hougaard, Karin Sørig; Hass, Ulla

doi:10.1093/toxsci/kfr006

Cited by 110 publications

(60 citation statements)

References 30 publications

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“…Another pesticide, mancozeb, underwent the same network analysis and was found to be associated with, for example, inflammatory targets and had no targets in common with prochloraz or other tested pesticides [20]. This outcome is also in line with our experimental data [42] and gives confidence in applying this approach on chemicals for which no animal data exist.…”

Section: A Case Study: Computational Systems Biology Applied On Prochsupporting

confidence: 76%

Applicability of Computational Systems Biology in Toxicology

Kongsbak

Hadrup

Audouze

et al. 2014

Basic Clin Pharma Tox

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Systems biology as a research field has emerged within the last few decades. Systems biology, often defined as the antithesis of the reductionist approach, integrates information about individual components of a biological system. In integrative systems biology, large data sets from various sources and databases are used to model and predict effects of chemicals on, for instance, human health. In toxicology, computational systems biology enables identification of important pathways and molecules from large data sets; tasks that can be extremely laborious when performed by a classical literature search. However, computational systems biology offers more advantages than providing a high-throughput literature search; it may form the basis for establishment of hypotheses on potential links between environmental chemicals and human diseases, which would be very difficult to establish experimentally. This is possible due to the existence of comprehensive databases containing information on networks of human protein-protein interactions and protein-disease associations. Experimentally determined targets of the specific chemical of interest can be fed into these networks to obtain additional information that can be used to establish hypotheses on links between the chemical and human diseases. Such information can also be applied for designing more intelligent animal/cell experiments that can test the established hypotheses. Here, we describe how and why to apply an integrative systems biology method in the hypothesis-generating phase of toxicological research. What is Computational Systems Biology?Systems biology is often defined as the antithesis of the reductionist approach. Although the reductionist approach has identified many important individual components of biological systems, it often fails to integrate the interconnections between the individual components. Systems biology, on the other hand, deals with the integration of information from a wealth of individual components, creating a holistic view of the biological system [1]. Each component is made up by larger or smaller data sets. For instance, analysis of microarray experiments gives quantitative estimates of changes in expression of a whole-organism genome. High-throughput screening and high-content screening are procedures giving biological activity data on a large number of chemicals (e.g. the U.S. Environmental Protection Agency's ToxCast programme [2]). Additionally, low-/medium-throughput single-target assays provide high-quality measures of the biological function of a single or more targets after chemical exposure. Combining such complementary data types may add value in creating realistic models of potential toxic or adverse effects of chemicals [3,4]. A key strategy to handle multiple data sources is data integration, the use of which has been demonstrated in several applications as reviewed by Mitra et al. [5], for example for the identification of new biomarkers for Alzheimer's disease [6].Computational toxicology integrates molecular...

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Section: A Case Study: Computational Systems Biology Applied On Prochsupporting

confidence: 76%

Applicability of Computational Systems Biology in Toxicology

Kongsbak

Hadrup

Audouze

et al. 2014

Basic Clin Pharma Tox

View full text Add to dashboard Cite

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“…Many pesticides may act through endocrine pathways, including maneb/mancozeb (Axelstad et al 2011; Bisson and Hontela 2002), DDT (McKinlay et al 2008), and glyphosate-containing products (Gasnier et al 2009; Richard et al 2005). Some previous studies reported an RA–farming association seen primarily in men (Lee et al 2002; Li et al 2008; Lundberg et al 1994; Milham 1988; Olsson et al 2000).…”

Section: Discussionmentioning

confidence: 99%

Rheumatoid Arthritis in Agricultural Health Study Spouses: Associations with Pesticides and Other Farm Exposures

Parks

Hoppin

Roos

et al. 2016

Environ Health Perspect

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Background:Farming has been associated with rheumatoid arthritis (RA), but the role of pesticides is not known.Objectives:We examined associations between RA and pesticides or other agricultural exposures among female spouses of licensed pesticide applicators in the Agricultural Health Study.Methods:Women were enrolled between 1993 and 1997 and followed through 2010. Cases (n = 275 total, 132 incident), confirmed by a physician or by self-reported use of disease modifying antirheumatic drugs, were compared with noncases (n = 24,018). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models adjusted for age, state, and smoking pack-years.Results:Overall, women with RA were somewhat more likely to have reported lifetime use of any specific pesticide versus no pesticides (OR = 1.4; 95% CI: 1.0, 1.6). Of the 15 pesticides examined, maneb/mancozeb (OR = 3.3; 95% CI: 1.5, 7.1) and glyphosate (OR = 1.4; 95% CI: 1.0, 2.1) were associated with incident RA compared with no pesticide use. An elevated, but non-statistically significant association with incident RA was seen for DDT (OR = 1.9; 95% CI: 0.97, 3.6). Incident RA was also associated with the application of chemical fertilizers (OR = 1.7; 95% CI: 1.1, 2.7) and cleaning with solvents (OR = 1.6; 95% CI: 1.1, 2.4), but inversely associated with lifetime livestock exposure as a child and adult (OR = 0.48; 95% CI: 0.24, 0.97) compared with no livestock exposure.Conclusions:Our results suggest that specific agricultural pesticides, solvents, and chemical fertilizers may increase the risk of RA in women, while exposures involving animal contact may be protective.Citation:Parks CG, Hoppin JA, De Roos AJ, Costenbader KH, Alavanja MC, Sandler DP. 2016. Rheumatoid arthritis in Agricultural Health Study spouses: associations with pesticides and other farm exposures. Environ Health Perspect 124:1728–1734; http://dx.doi.org/10.1289/EHP129

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“…Thiourea, which is structurally very similar to urea, is a powerful scavenger of hydroxyl radicals [27] . Urinary thiourea concentration is considered as a well-established biomarker for the assessment of thyroid disease [28] . Fustinoni et al [29] have identified the determination of urinary ethylenethiourea in humans by GC/MS.…”

Section: Discussionmentioning

confidence: 99%

Urinary Volatile Organic Compounds as Potential Biomarkers in Idiopathic Membranous Nephropathy

et al. 2017

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Objective: To detect urinary volatile organic compounds (VOCs) in patients with idiopathic membranous nephropathy (iMN) and normal controls, and to examine whether or not urinary VOCs can act as biomarkers for the diagnosis of iMN independent of renal biopsy. Materials and Methods: Gas chromatography/mass spectrometry (GC/MS) was used to assess the urine collected from 63 iMN patients and 15 normal controls. The statistical methods of principal component analysis and partial least squares discriminant analysis were performed to process the final data in Common Data Format which were converted from GC/MS data. Results: Six VOCs in the urine samples of iMN patients exhibited significant differences from those of normal controls: carbamic acid monoammonium salt, 2-pentanone, 2,4-dimethyl-pentanal, hydrogen azide, thiourea, and 4-heptanone were significantly higher than in controls (p < 0.05). Conclusions: Six urinary VOCs were isolated from patients with iMN using GC/MS. The analysis of urinary VOCs using GC/MS could be developed into a non-invasive method for the detection of iMN.

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Exposure to the Widely Used Fungicide Mancozeb Causes Thyroid Hormone Disruption in Rat Dams but No Behavioral Effects in the Offspring

Cited by 110 publications

References 30 publications

Applicability of Computational Systems Biology in Toxicology

Applicability of Computational Systems Biology in Toxicology

Rheumatoid Arthritis in Agricultural Health Study Spouses: Associations with Pesticides and Other Farm Exposures

Urinary Volatile Organic Compounds as Potential Biomarkers in Idiopathic Membranous Nephropathy

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