<i>In vitro</i>myelotoxic effects of cypermethrin and mancozeb on human hematopoietic progenitor cells

Mandarapu, Rajesh; Prakhya, Balakrishna Murthy

doi:10.3109/1547691x.2014.880535

Cited by 21 publications

(8 citation statements)

References 32 publications

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“…The pancytopenia observed in the exposed mice was linked to defects of the bone marrow stromal cells29. In addition the exposure of hematopoietic stem cells from human cord blood to mancozeb reduced the clonogenic potential of erythroid and granulocyte-macrophage progenitors40. Here, we confirmed these effects in a realistic exposure scenario and we propose a molecular mechanism behind the observed phenotype consisting in the inhibition of Egr1 , Hmga1 and Zfp36l2 transcripts.…”

Section: Discussionsupporting

confidence: 70%

Pesticide toxicogenomics across scales: in vitro transcriptome predicts mechanisms and outcomes of exposure in vivo

Porreca

D’Angelo

Franceschi

et al. 2016

Sci Rep

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In vitro Omics analysis (i.e. transcriptome) is suggested to predict in vivo toxicity and adverse effects in humans, although the causal link between high-throughput data and effects in vivo is not easily established. Indeed, the chemical-organism interaction can involve processes, such as adaptation, not established in cell cultures. Starting from this consideration we investigate the transcriptomic response of immortalized thyrocytes to ethylenthiourea and chlorpyrifos. In vitro data revealed specific and common genes/mechanisms of toxicity, controlling the proliferation/survival of the thyrocytes and unrelated hematopoietic cell lineages. These results were phenotypically confirmed in vivo by the reduction of circulating T4 hormone and the development of pancytopenia after long exposure. Our data imply that in vitro toxicogenomics is a powerful tool in predicting adverse effects in vivo, experimentally confirming the vision described as Tox21c (Toxicity Testing in the 21st century) although not fully recapitulating the biocomplexity of a living animal.

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Section: Discussionsupporting

confidence: 70%

Pesticide toxicogenomics across scales: in vitro transcriptome predicts mechanisms and outcomes of exposure in vivo

Porreca

D’Angelo

Franceschi

et al. 2016

Sci Rep

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“…The robust association of RA with maneb/mancozeb is supported by a small body of experimental research on maneb immunotoxicity in vitro (Mandarapu et al 2014; Mandarapu and Prakhya 2015) and in vivo (Chung and Pyo 2005). Acute maneb immunotoxic effects in humans are thought to be limited (Corsini et al 2013), but chronic exposure has been associated with leukemia in a study of farm workers (Mills et al 2005).…”

Section: Discussionmentioning

confidence: 98%

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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“…Despite this, our results appear to be supported by limited experimental data indicating toxic effects of specific pesticides on bone marrow. For instance, insecticide cypermethrin (synthetic pyrethroid) inhibited erythroid and granulocyte-macrophage progenitors in vitro 31 , while low doses of the OP mevinphos caused destruction of progenitors in human and rat hematopoietic progenitor cells 32 . There is also experimental evidence that insecticides malathion (OP) and carbaryl (carbamate) may induce anemia, immunosuppression, and altered number of leukocytes and platelets in vivo 33,34 .…”

Section: Pesticide Use and Hematological Parametersmentioning

confidence: 99%

Occupational exposure to pesticides and hematological alterations: A survey of farm residents in the South of Brazil

Piccoli

Cremonese

Koifman

et al. 2019

Ciênc. saúde coletiva

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This study sought to investigate the association of exposure to organochlorine (OC) and non-persistent pesticides with hematological parameters in an agricultural population in Southern Brazil. A cross-sectional study was conducted with a random sample of 275 farm workers and their families in Farroupilha-RS. A questionnaire was used to collect information on sociodemographic and lifestyle factors, duration, frequency and type of pesticide used, among others. Blood samples were collected and analyzed for serum concentration of 24 OC pesticides and hematological parameters. Associations were explored through linear regression, controlling for confounders. Lifetime use of chemical classes other than organophosphates and dithiocarbamates were associated with decreased number of lymphocytes, while subjects sampled in the high pesticide use season showed higher number of erythrocytes and hemoglobin level. Detectable serum levels of many OC pesticides were associated with lower counts of white blood cells, particularly eosinophils. Although mostly null associations were observed between pesticide use and hematological parameters, findings may suggest that OC pesticides could lead to hematological alterations among agricultural workers.

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In vitromyelotoxic effects of cypermethrin and mancozeb on human hematopoietic progenitor cells

Cited by 21 publications

References 32 publications

Pesticide toxicogenomics across scales: in vitro transcriptome predicts mechanisms and outcomes of exposure in vivo

Pesticide toxicogenomics across scales: in vitro transcriptome predicts mechanisms and outcomes of exposure in vivo

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

Occupational exposure to pesticides and hematological alterations: A survey of farm residents in the South of Brazil

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