Hepatic Enzyme Induction

Maronpot, Robert R.; Yoshizawa, Katsuhiko; Nyska, Abraham; Harada, Takanori; Flake, Gordon P.; Mueller, Gundi; Singh, Bhanu; Ward, Jerrold M.

doi:10.1177/0192623310373778

Cited by 168 publications

(124 citation statements)

References 98 publications

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“…functional, morphological, and molecular changes that indicate or precede the full establishment of neoplasia, such as enzyme induction, hepatocyte hypertrophy, degeneration and necrosis, hepatocyte proliferation, altered hepatocellular foci, etc. (Williams 1980;Bannasch et al 2003;Maronpot et al 2010). Identification and analyses of these liver changesthat span from adaptive to irreversible toxic effects -can help support characterization of key events along the carcinogenesis process and inform the mode of action of the tested chemical (Williams & Iatropoulos 2002;Holsapple et al 2006;Carmichael et al 2011).…”

Section: Liver Tumors In Ratsmentioning

confidence: 99%

A review of the carcinogenic potential of glyphosate by four independent expert panels and comparison to the IARC assessment

Williams

Aardema²,

Acquavella

et al. 2016

Critical Reviews in Toxicology

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The International Agency for Research on Cancer (IARC) published a monograph in 2015 concluding that glyphosate is "probably carcinogenic to humans" (Group 2A) based on limited evidence in humans and sufficient evidence in experimental animals. It was also concluded that there was strong evidence of genotoxicity and oxidative stress. Four Expert Panels have been convened for the purpose of conducting a detailed critique of the evidence in light of IARC's assessment and to review all relevant information pertaining to glyphosate exposure, animal carcinogenicity, genotoxicity, and epidemiologic studies. Two of the Panels (animal bioassay and genetic toxicology) also provided a critique of the IARC position with respect to conclusions made in these areas. The incidences of neoplasms in the animal bioassays were found not to be associated with glyphosate exposure on the basis that they lacked statistical strength, were inconsistent across studies, lacked dose-response relationships, were not associated with preneoplasia, and/or were not plausible from a mechanistic perspective. The overall weight of evidence from the genetic toxicology data supports a conclusion that glyphosate (including GBFs and AMPA) does not pose a genotoxic hazard and therefore, should not be considered support for the classification of glyphosate as a genotoxic carcinogen. The assessment of the epidemiological data found that the data do not support a causal relationship between glyphosate exposure and nonHodgkin's lymphoma while the data were judged to be too sparse to assess a potential relationship between glyphosate exposure and multiple myeloma. As a result, following the review of the totality of the evidence, the Panels concluded that the data do not support IARC's conclusion that glyphosate is a "probable human carcinogen" and, consistent with previous regulatory assessments, further concluded that glyphosate is unlikely to pose a carcinogenic risk to humans. ARTICLE HISTORY

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Section: Liver Tumors In Ratsmentioning

confidence: 99%

A review of the carcinogenic potential of glyphosate by four independent expert panels and comparison to the IARC assessment

Williams

Aardema²,

Acquavella

et al. 2016

Critical Reviews in Toxicology

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“…Although BE did not affect the mean weight of the rats, the organ weights were significantly increased, and this may indicate its early toxic potential. According to Maronpot and co-workers 18 , the increased liver weight of the high-dose rats could be in response to hepatic enzyme induction, which is typically associated with hepatocellular hypertrophy and transient hepatocyte hyperplasia. The kidney weights in the 5 mg/kg and 3 mg/kg groups were 15% and 18% higher than the basal group, however these differences were not significant and may just reflect the slightly lower body weights of the animals in the high-dose treatment groups.…”

Section: Discussionmentioning

confidence: 99%

Alterations in morphology and hepatorenal indices in rats subacutely exposed to bitumen extract

et al. 2016

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Bitumen is a complex mixture of dense and extremely viscous organic liquids produced by distillation of crude oil during petroleum refining. Nigeria has a large deposit of natural bitumen, yet to be fully exploited. Discharges of petroleum hydrocarbons and other petroleum-derived products have caused environmental pollution and adverse human health effects in several oil-rich communities. In this study, bitumen obtained from a seepage source in Agbabu, the town of first discovery, was used in sub-acute toxicity studies in a rat experimental model, in order to assess potential health risks posed to local populace sequel to full exploitation of bitumen. Dosages were chosen to accommodate low to high cases of environmental exposures. Male Wistar rats were administered, per os, dosages of bitumen extract at 5, 3, 2, and 1 mg/kg body weight. Following euthanasia 28 days later, histological findings revealed severe portal congestion and cellular infiltration in the liver, while in the kidney there were protein casts in the tubular lumen. The relative liver and kidney weights in the 5 mg/kg groups were 34% and 40% higher than in the controls, with a concomitant decrease in food and water consumption. Furthermore, plasma clinical analyses revealed marked elevation in aspartate aminotransferase and triglycerides levels in bitumen extract-intoxicated rats. The results indicate the potential hepatorenal toxicity in adult rats following repeated exposure to bitumen extract. ARTICLE HISTORY

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“…For example, hepatocellular hypertrophy, an adaptive response related to enzyme induction in the liver, is known to recover (Maronpot et al 2010). Thus, if metabolism and/or toxicokinetic data support that liver weight increase and hepatocellular hypertrophy are due to test article-related enzyme induction then a recovery study is not needed.…”

Section: Distinction Between Adverse and Recoverymentioning

confidence: 99%

Society of Toxicologic Pathology Position Paper on Best Practices on Recovery Studies

et al. 2013

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This article reviews the regulatory guidelines that provide for the inclusion of recovery groups in toxicology studies, presents the challenges in the design and interpretation of nonclinical recovery studies, and summarizes the best practices for the role of an anatomic pathologist regarding toxicology studies with recovery groups. Evaluating the potential recovery of histopathologic findings induced by a biopharmaceutical requires the active participation of one or more anatomic pathologists. Their expertise is critical in risk assessment regarding the potential for recovery as well as providing scientific guidance in the design and evaluation of studies with recovery groups.

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Hepatic Enzyme Induction

Cited by 168 publications

References 98 publications

A review of the carcinogenic potential of glyphosate by four independent expert panels and comparison to the IARC assessment

A review of the carcinogenic potential of glyphosate by four independent expert panels and comparison to the IARC assessment

Alterations in morphology and hepatorenal indices in rats subacutely exposed to bitumen extract

Society of Toxicologic Pathology Position Paper on Best Practices on Recovery Studies

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