Evaluating the MoA/human relevance framework for F-344 rat liver epithelioid granulomas with mineral oil hydrocarbons
| العنوان: | Evaluating the MoA/human relevance framework for F-344 rat liver epithelioid granulomas with mineral oil hydrocarbons |
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| المؤلفون: | M. David Adenuga, Katy O. Goyak, R. Jeffrey Lewis |
| المصدر: | Critical Reviews in Toxicology. 47:754-770 |
| بيانات النشر: | Informa UK Limited, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Pathology, medicine.medical_specialty, Biology, Toxicology, Epithelioid granuloma, Intestinal absorption, 03 medical and health sciences, 0404 agricultural biotechnology, Species Specificity, medicine, Animals, Humans, Mineral Oil, Ingestion, Mode of action, Mineral oil, Pathological, Granuloma, Liver Neoplasms, 04 agricultural and veterinary sciences, medicine.disease, 040401 food science, Hydrocarbons, Rats, 030104 developmental biology, Liver, Rat liver, medicine.drug |
| الوصف: | Toxicology feeding studies of mineral oil hydrocarbons (MOHs), within the carbon number range C22-C28, results in species-specific epithelioid granulomas in the liver of F-344 rats but not in other rat strains, or species. While MOH has been detected, and some pathological effects have been shown to occur in other organs/tissues of F-344 rats and other rat strains/species, it is generally accepted that the effect of toxicological concern is species-specific inflammatory liver granuloma. As oil retention and other MOH-related nontoxic pathological changes in the liver are observed in humans, some have hypothesized that the potential for oil accumulation over a lifetime, through dietary sources, may predispose humans to similar liver effects as observed in F-344 rats. To address this concern, a mode of action/human relevance framework (MoA/HRF) analysis for MOH-induced epithelioid granuloma in the F-344 rat model was developed. The key events for the development of liver epithelioid granulomas were identified as increased MOH intestinal absorption, preferential tissue retention and ultimately formation of necrotic granulomas encased by infiltrating inflammatory lymphocytes. The hypothesized MoA was evaluated using the modified Bradford Hill considerations for causality and was considered to be established in the F-344 rodent model. However, key strain/species differences in the rate of intestinal absorption, tissue retention of MOH and inflammatory response to MOH in the liver were identified. Overall, the F-344 rat MoA was not considered to be relevant to humans, consistent with data showing no evidence for the formation of epithelioid granulomas with humans even in cases of massive ingestion of MOHs. |
| تدمد: | 1547-6898 1040-8444 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::348109c0fbf5bff53b106a97face0865 https://doi.org/10.1080/10408444.2017.1319336 |
| رقم الأكسشن: | edsair.doi.dedup.....348109c0fbf5bff53b106a97face0865 |
| قاعدة البيانات: | OpenAIRE |
PDF full text from Publisher | تدمد: | 15476898 10408444 |
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