Hypospadias and Residential Proximity to Pesticide Applications

Carmichael, Suzan L.; Yang, Wei; Roberts, Eric M.; Kegley, Susan E.; Wolff, Craig; Guo, Liang; Lammer, Edward J.; English, Paul; Shaw, Gary M.

doi:10.1542/peds.2013-1429

Cited by 52 publications

(41 citation statements)

References 41 publications

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“…In short term acute exposures, some adjuvants can be considered as responsible of Roundup toxicity42. Populations of farmers exposed to adjuvants, such as solvents or petroleum distillates, possess a higher risk of developing hypospadias43 and present with more allergic and non-allergic wheeze conditions44. However, as adjuvant composition is proprietary and not fully disclosed, it is not possible to attribute the toxicity of the whole agricultural herbicide formulation to a given component.…”

Section: Discussionmentioning

confidence: 99%

Multiomics reveal non-alcoholic fatty liver disease in rats following chronic exposure to an ultra-low dose of Roundup herbicide

Mesnage

Renney

Séralini

et al. 2017

Sci Rep

161

100

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The impairment of liver function by low environmentally relevant doses of glyphosate-based herbicides (GBH) is still a debatable and unresolved matter. Previously we have shown that rats administered for 2 years with 0.1 ppb (50 ng/L glyphosate equivalent dilution; 4 ng/kg body weight/day daily intake) of a Roundup GBH formulation showed signs of enhanced liver injury as indicated by anatomorphological, blood/urine biochemical changes and transcriptome profiling. Here we present a multiomic study combining metabolome and proteome liver analyses to obtain further insight into the Roundup-induced pathology. Proteins significantly disturbed (214 out of 1906 detected, q < 0.05) were involved in organonitrogen metabolism and fatty acid β-oxidation. Proteome disturbances reflected peroxisomal proliferation, steatosis and necrosis. The metabolome analysis (55 metabolites altered out of 673 detected, p < 0.05) confirmed lipotoxic conditions and oxidative stress by showing an activation of glutathione and ascorbate free radical scavenger systems. Additionally, we found metabolite alterations associated with hallmarks of hepatotoxicity such as γ-glutamyl dipeptides, acylcarnitines, and proline derivatives. Overall, metabolome and proteome disturbances showed a substantial overlap with biomarkers of non-alcoholic fatty liver disease and its progression to steatohepatosis and thus confirm liver functional dysfunction resulting from chronic ultra-low dose GBH exposure.

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Section: Discussionmentioning

confidence: 99%

Multiomics reveal non-alcoholic fatty liver disease in rats following chronic exposure to an ultra-low dose of Roundup herbicide

Mesnage

Renney

Séralini

et al. 2017

Sci Rep

161

100

View full text Add to dashboard Cite

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“…Nevertheless, it should be noted that such studies are most useful for generating hypotheses rather than assessing true cause-effect relationships at an individual level (Agopian et al, 2013a; Carmichael et al, 2013; Giordano et al, 2010). This limitation was apparent when the positive results of an ecological study in Sicily could not be replicated by a following case-control study conducted by the same authors on the same population (Carbone et al, 2007).…”

Section: Urogenital Abnormalitiesmentioning

confidence: 99%

“…Ecological studies aside, results were ambiguous; with three studies supporting a positive association (Agopian et al., 2013a; Carmichael et al, 2013; Giordano et al, 2010) and four studies negating it (Brouwers et al, 2007; Carbone et al, 2007; Dugas et al, 2010; Meyer et al, 2006). The primary risk factor was maternal exposure (Agopian et al, 2013a; Giordano et al, 2010).…”

Section: Urogenital Abnormalitiesmentioning

confidence: 99%

Association of pesticide exposure with human congenital abnormalities

Kalliora

Mamoulakis

Vasilopoulos

et al. 2018

Toxicology and Applied Pharmacology

109

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Human pesticide exposure can occur both occupationally and environmentally during manufacture and after the application of indoor and outdoor pesticides, as well as through consumption via residues in food and water. There is evidence from experimental studies that numerous pesticides, either in isolation or in combination, act as endocrine disruptors, neurodevelopmental toxicants, immunotoxicants, and carcinogens. We reviewed the international literature on this subject for the years between 1990 and 2017. The studies were considered in this review through MEDLINE and WHO resources. Out of the n = 1817 studies identified, n = 94 were reviewed because they fulfilled criteria of validity and addressed associations of interest. Epidemiological studies have provided limited evidence linking pre- and post-natal exposure to pesticides with cancers in childhood, neurological deficits, fetal death, intrauterine growth restriction, preterm birth, and congenital abnormalities (CAs). In this review, the potential association between pesticide exposure and the appearance of some human CAs (including among others musculoskeletal abnormalities; neural tube defects; urogenital and cardiovascular abnormalities) was investigated. A trend towards a positive association between environmental or occupational exposure to some pesticides and some CAs was detected, but this association remains to be substantiated. Main limitations of the review include inadequate exposure assessment and limited sample size. Adequately powered studies with precise exposure assessments such as biomonitoring, are warranted to clarify with certainty the potential association between pesticide exposure and human CAs.

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“…The study population included male infants born from 1991 to 2003 to mothers who were residents of eight California Central Valley counties (Fresno, Kern, Kings, Madera, Merced, San Joaquin, Stanislaus, and Tulare counties) and who were included in our previous studies of pesticides and genes and hypospadias (Carmichael et al, ; , , ). California Birth Defects Monitoring Program staff ascertained cases by reviewing medical records at hospitals and genetic centers (Croen et al, ).…”

Section: Methodsmentioning

confidence: 99%

“…We previously reported increased risk with residential proximity to a few, but not most, of many different pesticides that were studied (Carmichael et al, 2013b). Hypospadias is also highly heritable (Schnack et al, 2008), but the specific genes that contribute to risk are in large part unknown.…”

Section: Introductionmentioning

confidence: 99%

Joint effects of genetic variants and residential proximity to pesticide applications on hypospadias risk

Carmichael

Yang

et al. 2016

Birth Defects Research

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Hypospadias and Residential Proximity to Pesticide Applications

Abstract: Most pesticides were not associated with elevated hypospadias risk. For the few that were associated, results should be interpreted with caution until replicated in other study populations.

Cited by 52 publications

References 41 publications

Multiomics reveal non-alcoholic fatty liver disease in rats following chronic exposure to an ultra-low dose of Roundup herbicide

Multiomics reveal non-alcoholic fatty liver disease in rats following chronic exposure to an ultra-low dose of Roundup herbicide

Association of pesticide exposure with human congenital abnormalities

Joint effects of genetic variants and residential proximity to pesticide applications on hypospadias risk

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