Gavage-Related Reflux in Rats

Damsch, S; Eichenbaum, Gary; Tonelli, Alfred; Lammens, Lieve; Bulck, Kathleen Van den; Feyen, Bianca; Vandenberghe, J; Megens, Anton; Knight, Enid M.; Kelley, Michael F.

doi:10.1177/0192623310388431

Cited by 90 publications

(37 citation statements)

References 40 publications

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“…For example, a common complication with gavage involves perforation of the esophagus or stomach [41]. Additional complications involve the accidental introduction of fluids into the trachea or lungs, asphyxia, inflammation, weight loss, hemorrhage, and reflux [41,50]. Other studies report high frequencies of morbidity and mortality due to the use of gavage; several report rates greater than 50% [38].…”

Section: Introductionmentioning

confidence: 99%

Should oral gavage be abandoned in toxicity testing of endocrine disruptors?

et al. 2014

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For decades, hazard assessments for environmental chemicals have used intra-gastric gavage to assess the effects of ‘oral’ exposures. It is now widely used – and in some cases required – by US federal agencies to assess potential toxicity of endocrine disrupting chemicals (EDCs). In this review we enumerate several reasons why gavage is not appropriate for the assessment of EDCs using bisphenol A (BPA) as a main example. First, whereas human dietary exposures interact with the oral mucosa, gavage exposures avoid these interactions, leading to dramatic differences in absorption, bioavailability and metabolism with implications for toxicokinetic assumptions and models. Additionally, there are well acknowledged complications associated with gavage, such as perforation of the esophagus that diminish its value in toxicological experiments. Finally, the gavage protocol itself can induce stress responses by the endocrine system and confound the assessment of EDCs. These serious flaws have not been taken into account in interpreting results of EDC research. We propose the exploration of alternatives to mimic human exposures when there are multiple exposure routes/sources and when exposures are chronic. We conclude that gavage may be preferred over other routes for some environmental chemicals in some circumstances, but it does not appropriately model human dietary exposures for many chemicals. Because it avoids exposure pathways, is stressful, and thus interferes with endocrine responses, gavage should be abandoned as the default route of administration for hazard assessments of EDCs.

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Section: Introductionmentioning

confidence: 99%

Should oral gavage be abandoned in toxicity testing of endocrine disruptors?

et al. 2014

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“…Owing to the nature of the test substance, gavage-related reflux is known to occur more often than expected, and is mediated by increased viscosity, irritancy, and/or stability problems (e.g., high lipophilicity and acids) (6); thus, the death might be attributed to the gavage-related reflux considering the clinical signs and time of death.…”

Section: Resultsmentioning

confidence: 99%

Reproductive and Developmental Toxicity Screening Test of Ethyl Hydrogen Adipate in Rats

Nam¹,

Hwang²,

Han³

et al. 2016

ToxicolRes

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This study aimed to evaluate the potential toxicity and safety of ethyl hydrogen adipate (EHA) by determining its effect on the reproductive function and development of Sprague-Dawley (SD) rats at dose levels of 0 (control), 200, 400, and 800 mg/kg/day. One male and five females of the 800 mg/kg/day died. Body weight loss was observed in the males of the 800 mg/kg/day and in females of the 400 and 800 mg/kg/day. In addition, mating indices decreased and pre-implantation loss rates increased in parental animals of the 400 and 800 mg/kg/day. The gestation index decreased in the male and female rats of the 800 mg/kg/day. Moreover, the body weight of the pups from the 800 mg/kg/day group decreased on post-parturition day 4. These results indicated that the no-observed-adverse-effect level of EHA for parental males and females was 400 mg/kg/day and 200 mg/kg/day, respectively, and that for pups was 400 mg/kg/day.

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“…Mechanically induced reflux occurs directly after the gavage when withdrawing the tube from the animal and spontaneous reflux occurs not only directly after gavage, but also later, when the animal is back in its cage. The later reflux is related to the administration of a large volume by gavage (5-10 mL) (17). However, regarding gavage-related reflux and technical gavage errors, it is now considered that even very small amounts of the treated material, 20 µl, are able to induce serious irritation in the respiratory tract and mortality.…”

Section: Discussionmentioning

confidence: 99%

“…Lungs of all rats from the treated groups at all times of sacrifice presented morphological alterations that could be induced by gavage-related reflux (17). Some bronchus showed pyogenic infiltrates and others presented large vacuolated macrophages inside.…”

Section: Lungsmentioning

confidence: 95%

Hepatic preneoplasia induction in male Wistar rats: histological studies up to five months post treatment

2016

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Background: Liver preneoplasia development in rats can be mimicked by an initiation-promotion model that induces the appearance of altered hepatocyte foci (FAH).Aims: We compare two initiation-promotion models to evaluate the presence of FAH or additional hepatic pathologies in which other organs were affected up to five month post treatment.Material and methods: FAH were induced in male adult Wistar rats with two doses of dietylnitrosamine (DEN, 150 mg/kg bw) followed by 4 doses per week (3 weeks) of 2-acetylaminofluorene (2-AAF, 20 mg/kg bw) or with one dose of DEN (200 mg/kg bw) followed by 2 doses per week (3 weeks) of 2-AAF. DEN 150, DEN 200 and control rats (received the vehicle of the drugs) groups were compared. Rats were euthanized immediately after the last dose of 2-AAF, at 3, 4 and 5 months (n = 3 for euthanasia times per group). Samples of livers, lungs, kidneys, pancreatic tissue and small bowel were processed for histological and immunohistochemical analysis.Results: FAH persisted for 5 months in all livers of the DEN groups. Three months after withdrawal of 2-AAF, one rat from DEN 150 group developed fibrosis and 5 months after 2-AAF removal another rat from the same group presented a microscopic hyperplastic nodule. Only the lungs had damages compatible with lesions induced by gavage-related reflux in DEN groups.Conclusion: We concluded that up to five month post treatments, FAH persisted in all the livers from DEN groups; livers from DEN 200 group showed no other hepatic lesions besides FAH, and only the lungs suffered pathological alterations in both treated groups.

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Gavage-Related Reflux in Rats

Cited by 90 publications

References 40 publications

Should oral gavage be abandoned in toxicity testing of endocrine disruptors?

Should oral gavage be abandoned in toxicity testing of endocrine disruptors?

Reproductive and Developmental Toxicity Screening Test of Ethyl Hydrogen Adipate in Rats

Hepatic preneoplasia induction in male Wistar rats: histological studies up to five months post treatment

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