Induction of Transitional Cell Hyperplasia in the Urinary Bladder and Aberrant Crypt Foci in the Colon of Rats Treated with Individual and a Mixture of Drinking Water Disinfection By-Products

McDorman, Kevin S.; Chandra, Sundeep; Hooth, Michelle J.; Hester, Susan; Schoonhoven, Robert; Wolf, Douglas C.

doi:10.1080/01926230390183733

Cited by 15 publications

(3 citation statements)

References 40 publications

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“…The tissues were stained for the presence of proliferating cell nuclear antigen (PCNA) as previously described (McDorman et al, 2003). The cells were counted using counting software, Cytology Histology Recognition Information System (CHRIS, Sverdrup, Fort Walton Beach, FL) as previously reported (Medinsky et al, 1999).…”

Section: Histologymentioning

confidence: 99%

Toxicity Profiles in Rats Treated with Tumorigenic and Nontumorigenic Triazole Conazole Fungicides: Propiconazole, Triadimefon, and Myclobutanil

et al. 2006

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Conazoles are a class of azole based fungicides used in agriculture and as pharmaceutical products. They have a common mode of antifungal action through inhibition of ergosterol biosynthesis. Some members of this class have been shown to be hepatotoxic and will induce mouse hepatocellular tumors and/or rat thyroid follicular cell tumors. The particular mode of toxic and tumorigenic action for these compounds is not known, however it has been proposed that triadimefon-induced rat thyroid tumors arise through the specific mechanism of increased TSH. The present study was designed to identify commonalities of effects across the different conazoles and to determine unique features of the tissue responses that suggest a toxicity pathway and a mode of action for the observed thyroid response for triadimefon. Male Wistar/Han rats were treated with triadimefon (100, 500, 1800 ppm), propiconazole (100, 500, 2500 ppm), or myclobutanil (100, 500, 2000 ppm) in feed for 4, 30, or 90 days. The rats were evaluated for clinical signs, body and liver weight, histopathology of thyroid and liver, hepatic metabolizing enzyme activity, and serum T3, T4, TSH, and cholesterol levels. There was a dose-dependent increase in liver weight but not body weight for all treatments. The indication of cytochrome induction, pentoxyresorufin O-dealkylation (PROD) activity, had a dose-related increase at all time points for all conazoles. Uridine diphopho-glucuronosyl transferase (UDPGT), the T4 metabolizing enzyme measured as glucuronidation of 1-naphthol, was induced to the same extent after 30 and 90 days for all three conazoles. Livers from all high dose treated rats had centrilobular hepatocyte hypertrophy after 4 days, while only triadimefon and propiconazole treated rats had hepatocyte hypertrophy after 30 days, and only triadimefon treated rats had hepatocyte hypertrophy after 90 days. Thyroid follicular cell hypertrophy, increased follicular cell proliferation, and colloid depletion were present only after 30 days in rats treated with the high dose of triadimefon. A dose-dependent decrease in T4 was present after 4 days with all 3 compounds but only the high doses of propiconazole and triadimefon produced decreased T4 after 30 days. T3 was decreased after high-dose triadimefon after 4 days and in a dose-dependent manner for all compounds after 30 days. Thyroid hormone levels did not differ from control values after 90 days and TSH was not increased in any exposure group. A unique pattern of toxic responses was not identified for each conazole and the hypothesized mode of action for triadimefon-induced thyroid gland tumors was not supported by the data.

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Section: Histologymentioning

confidence: 99%

Toxicity Profiles in Rats Treated with Tumorigenic and Nontumorigenic Triazole Conazole Fungicides: Propiconazole, Triadimefon, and Myclobutanil

et al. 2006

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“…In a 1994 assessment of potassium bromate and sodium bromate, the Cosmetic Ingredient Review (CIR) Expert Panel stated that these ingredients may be used in cosmetic permanent wave formulations at concentrations not to exceed 10.17%, measured as sodium bromate. 1 The Expert Panel reviewed newly available studies since that assessment, along with updated information regarding types and concentrations of use 2…”

Section: Resultsmentioning

confidence: 99%

Annual Review of Cosmetic Ingredient Safety Assessments: 2007-2010

Andersen¹

2011

Int J Toxicol

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This Annual Review of Cosmetic Ingredient Safety Assessments updates and affirms the findings of the Cosmetic Ingredient Review (CIR) Expert Panel's assessment of almost 30 compounds used in cosmetic ingredients. The review also summarizes new findings from epidemiology studies of hair dyes. The CIR Expert Panel's re-review process is intended to uncover any new data since the last safety assessment. In some cases, newly available data are largely redundant compared with the data available in the original safety assessment. In other cases, new data present new safety issues. If after considering the newly available information, the CIR Expert Panel decides to not reopen a safety assessment, this finding, along with any background material, is summarized and announced publicly. To assure that the scientific community is aware of any new information and the decision not to reopen, this Annual Review of Cosmetic Ingredient Safety Assessments is prepared. A list of reference sources is provided after each ingredient re-review summary that updates the available published literature and includes any unpublished data made available since the original safety assessment. The re-review also captures information on the industry's current practices of ingredient use, updating the data available in the earlier report. Although this material provides the opinion of the CIR Expert Panel regarding the new data described, it does not constitute a full safety review. The CIR Expert Panel has assessed the safety of over 2100 cosmetic ingredients since its inception in 1976. These safety assessments were published in the

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“…A positive reaction was indicated by a red color. Sections were scored as previously described (42). Briefly, 20 intact crypts in both the descending colon and rectum were identified for each animal (3 animals per group) and the total number of cells with positive nuclear staining was counted.…”

Section: Animals Cryopreserved Embryos Ofmentioning

confidence: 99%

Knockout ofMkp-1exacerbates colitis inIl-10-deficient mice

Matta

Barnard

Wancket

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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Il-10-deficient mice develop colitis associated with exaggerated Th1/Th17 responses and are a valuable model of inflammatory bowel disease. Mkp-1 is a major negative regulator of MAPKs, and its expression is enhanced by IL-10. To understand the role of Mkp-1 in the regulation of intestinal mucosal immune responses, we studied the effect of Mkp-1 deletion on the pathogenesis of colitis in Il-10−/−mice. We found that knockout of Mkp-1 on an Il-10−/−background accelerated the development of colitis. Compared with Il-10−/−mice, colitis not only appeared earlier but also was more severe in Il-10−/−/ Mkp-1−/−mice. Il-10−/−mice exhibited a mild intestinal inflammation in the specific pathogen-free environment, and rectal prolapse rarely appeared before 6 mo of age. In contrast, the majority of Il-10−/−/ Mkp-1−/−mice developed severe colitis rapidly and presented with rectal prolapse after only 2–3 mo. The colon of Il-10−/−/ Mkp-1−/−mice showed diffuse transmural chronic inflammation and mucosal hyperplasia, with significantly more proliferating crypt epithelial cells than those of Il-10−/−mice. In addition to the severe colitis, Il-10−/−/ Mkp-1−/−mice also developed conjunctivitis and blepharitis. The colon of Il-10−/−/ Mkp-1−/−mice contained significantly higher levels of proinflammatory cytokines and exhibited greater MAPK activities than did the colon of Il-10−/−mice. Splenocytes and lymphocytes from Il-10−/−/ Mkp-1−/−mice produced higher levels of Th1 cytokines ex vivo upon activation than did cells from Il-10−/−mice. Our studies support a pivotal role of Mkp-1 as a negative regulator of mucosal immune responses and highlight its protective function against inflammatory bowel disease.

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Induction of Transitional Cell Hyperplasia in the Urinary Bladder and Aberrant Crypt Foci in the Colon of Rats Treated with Individual and a Mixture of Drinking Water Disinfection By-Products

Cited by 15 publications

References 40 publications

Toxicity Profiles in Rats Treated with Tumorigenic and Nontumorigenic Triazole Conazole Fungicides: Propiconazole, Triadimefon, and Myclobutanil

Toxicity Profiles in Rats Treated with Tumorigenic and Nontumorigenic Triazole Conazole Fungicides: Propiconazole, Triadimefon, and Myclobutanil

Annual Review of Cosmetic Ingredient Safety Assessments: 2007-2010

Knockout ofMkp-1exacerbates colitis inIl-10-deficient mice

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