Hepatotoxicity of the pesticides imazalil, thiacloprid and clothianidin – Individual and mixture effects in a 28-day study in female Wistar rats

Alarcan, Jimmy; Waizenegger, Julia; Solano, Marize de Lourdes Marzo; Lichtenstein, Dajana; Luckert, Claudia; Peijnenburg, Ad; Stoopen, Geert; Sharma, Raju Prasad; Kumar, Vikas; Marx‐Stoelting, Philip; Lampen, Alfonso; Braeuning, Albert

doi:10.1016/j.fct.2020.111306

Cited by 36 publications

(17 citation statements)

References 25 publications

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“…Detailed description of study design can be found in Alarcan et al (2020). Briefly, young adult female Wistar rats (Crl:WI) were acclimatized to the laboratory conditions for at least 1 week and were weighed and monitored for their health status.…”

Section: Animals and Treatmentmentioning

confidence: 99%

“…We have recently published the outcome of a 28-day oral study in female Wistar rats with the three pesticidal active compounds imazalil (IMZ), thiacloprid (THI) and clothianidin (CTD) (Alarcan et al 2020). Those substances have been assigned to the CAG liver toxicity and recent exposure studies revealed a predominant occurrence in food or even in human urine samples, thus raising a concern about safety (Craddock et al 2019;Crepet et al 2019;Nielsen et al 2012).…”

Section: Introductionmentioning

confidence: 99%

“…Reported effects included an increase in liver weight, hepatocellular hypertrophy and cytoplasmic changes of the hepatocytes. Additionally, liver and kidney residue analysis showed alterations in pesticide residues when applied in mixtures as compared to the levels of pesticide residues for the single compound treatment (Alarcan et al 2020).…”

Section: Introductionmentioning

confidence: 99%

“…The present study constitutes a follow-up to the previous publication of pesticide hepatotoxicity in vivo (Alarcan et al 2020) and aims to investigate the molecular effects of pesticides in rat liver, both individually and in combination. To this end, we undertook a transcriptomics analysis using total RNA sequencing (RNA-Seq).…”

Section: Introductionmentioning

confidence: 99%

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Transcriptomics analysis of hepatotoxicity induced by the pesticides imazalil, thiacloprid and clothianidin alone or in binary mixtures in a 28-day study in female Wistar rats

et al. 2021

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Co-occurrence of pesticide residues in food commodities raises a potential safety issue as their mixture effects on human health are largely unknown. In a previous study, we reported the toxicological effects (pathology and histopathology) of imazalil (IMZ), thiacloprid (THI), and clothianidin (CTD) alone and in binary mixtures in a 28-day oral gavage study in female Wistar rats. Five dose levels (up to 350 mg/kg body weight/day) ranging from a typical toxicological reference value to a clear effect dose were applied. In the present study, we undertook a transcriptomics analysis of rat livers by means of total RNA sequencing (RNA-Seq). Bioinformatic data analysis involving Ingenuity Pathway Analysis (IPA) was used to gain mechanistic information on hepatotoxicity-related pathways affected after treatment with the pesticides, alone and in mixtures. Our data show that 2986 genes were differentially regulated by CTD while IMZ and THI had effects on 194 and 225 genes, respectively. All three individual compounds shared a common subset of genes whose network is associated with xenobiotic metabolism and nuclear receptor activation. Similar networks were retrieved for the mixtures. Alterations in the expression of individual genes were in line with the assumption of dose addition. Our results bring new insight into the hepatotoxicity mechanisms of IMZ, THI, and CTD and their mixtures.

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Section: Animals and Treatmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Transcriptomics analysis of hepatotoxicity induced by the pesticides imazalil, thiacloprid and clothianidin alone or in binary mixtures in a 28-day study in female Wistar rats

et al. 2021

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“…However, overuse of these synthetic substances may have a long influence on environmental pollution and human health issues. The reported liver effects of pesticide and herbicide residues include hepatocellular hypertrophy and cytoplasm degeneration, obstructive cholestasis, decreased acetylcholinesterase activity, and hepatic mitochondrial toxicity [ 114 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 ].…”

Section: Nonphyto-hepatotoxins From Hmpsmentioning

confidence: 99%

Potential Hepatotoxins Found in Herbal Medicinal Products: A Systematic Review

Quan

Xuan

Teschke

2020

IJMS

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The risk of liver injury associated with the use of herbal medicinal products (HMPs) is well known among physicians caring for patients under a HMP therapy, as documented in case reports or case series and evidenced by using the Roussel Uclaf Causality Assessment Method (RUCAM) to verify a causal relationship. In many cases, however, the quality of HMPs has rarely been considered regarding potential culprits such as contaminants and toxins possibly incriminated as causes for the liver injury. This review aims to comprehensively assemble details of tentative hepatotoxic contaminants and toxins found in HMPs. Based on the origin, harmful agents may be divided according two main sources, namely the phyto-hepatotoxin and the nonphyto-hepatotoxin groups. More specifically, phyto-hepatotoxins are phytochemicals or their metabolites naturally produced by plants or internally in response to plant stress conditions. In contrast, nonphyto-hepatotoxic elements may include contaminants or adulterants occurring during collection, processing and production, are the result of accumulation of toxic heavy metals by the plant itself due to soil pollutions, or represent mycotoxins, herbicidal and pesticidal residues. The phyto-hepatotoxins detected in HMPs are classified into eight major groups consisting of volatile compounds, phytotoxic proteins, glycosides, terpenoid lactones, terpenoids, alkaloids, anthraquinones, and phenolic acids. Nonphyto-hepatotoxins including metals, mycotoxins, and pesticidal and herbicidal residues and tentative mechanisms of toxicity are discussed. In conclusion, although a variety of potential toxic substances may enter the human body through HMP use, the ability of these toxins to trigger human liver injury remains largely unclear.

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Bovine Whole Blood Cells as a Biomarker Platform for Biological Toxicology: A Focus on Thiacloprid

Galdíková

Holečková²,

Schwarzbacherová³

2022

Biomarkers in Toxicology

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Hepatotoxicity of the pesticides imazalil, thiacloprid and clothianidin – Individual and mixture effects in a 28-day study in female Wistar rats

Cited by 36 publications

References 25 publications

Transcriptomics analysis of hepatotoxicity induced by the pesticides imazalil, thiacloprid and clothianidin alone or in binary mixtures in a 28-day study in female Wistar rats

Transcriptomics analysis of hepatotoxicity induced by the pesticides imazalil, thiacloprid and clothianidin alone or in binary mixtures in a 28-day study in female Wistar rats

Potential Hepatotoxins Found in Herbal Medicinal Products: A Systematic Review

Bovine Whole Blood Cells as a Biomarker Platform for Biological Toxicology: A Focus on Thiacloprid

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