Madhav G. Paranjpe

Incidence of Spontaneous and Urethane-Induced Tumors in a 26-Week Carcinogenicity Study in Tg.rasH2 Mice Sourced From CLEA, Japan

Madhav G. Paranjpe, Amod Kale, Narendra S. Deshmukh, C.C. Magar et autres

The Tg.rasH2 mouse is a validated bioassay system for evaluation of carcinogenic potential, and it is confirmed to be sensitive to both genotoxic and nongenotoxic carcinogens. This is also one of the models specified in ICH S1B Guidance, enabling 6-month carcinogenicity studies …

Granulocytosis, a Paraneoplastic Syndrome Associated With Non-Glandular Squamous Cell Carcinomas (NGSCC) in the Tg.rasH2 Studies

Madhav G. Paranjpe, Peter Mann, Melissa D. Denton

Non-glandular squamous cell carcinoma (NGSCC) is an extremely rare tumor in Tg.raH2 mice. There have been 5 NGSCC in 1615 control male mice (0.31%) and 2 NGSCC in 1560 control female mice (0.13%) on 26-week carcinogenicity studies, with a range of 0 …

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Proposal to Eliminate Urethane-Treated Positive Control Dose Groups in 26-Week Tg.rasH2 Carcinogenicity Studies

Madhav G. Paranjpe, Daniel G. Rudmann, Aaron M. Sargeant, Mark A. Morse et autres

Short-term (26 weeks) Tg.rasH2 mouse carcinogenicity studies have been conducted as an alternative model to the conventional 2-year mouse carcinogenicity studies, using urethane as a positive control material. In these studies, urethane was used at a dose of 1,000 mg/kg/dose, administered intraperitoneally …

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A Proposal for New Strategies in Dose Selection for 26-Week Tg.Rash2 Carcinogenicity Studies

Madhav G. Paranjpe, Tom J. Vidmar, Melissa D. Denton, Reem H. Elbekai et autres

Our experience indicates that extrapolation of doses from the maximum tolerated doses (MTD) derived from 4-week dose range finding (DRF) studies conducted in CByB6F1 may overpredict tolerability and undermine utility of the high-dose groups in 26-week carcinogenicity studies conducted in Tg.rasH2. In …

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A Comparison of Spontaneous Tumors in Tg.rasH2 Mice in 26-week Carcinogenicity Studies Conducted at a Single Test Facility during 2004 to 2012 and 2013 to 2018

Madhav G. Paranjpe, Jessica L. Belich, Peter C. Mann, Marie E. McKeon et autres

This article presents the historical control data of spontaneous tumors in Tg.rasH2 published in 2013 (2004-2012) and compares and contrasts it to more recent data collected from 2013 to 2018, reporting differences in the average percentage incidences or incidence ranges as well …

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The Antitussive Benzonatate Is Not Tumorigenic in Rodent Carcinogenicity Studies

Steve Teo, Madhav G. Paranjpe, Marie E. McKeon, Peter Mann et autres

Benzonatate is a peripheral oral antitussive that dampens the activity of cough stretch receptors. Rodent carcinogenicity studies were performed in Tg.rasH2 mice and Wistar Han rats. Mice were orally gavaged benzonatate at 10, 30, 75, and 100 mg/kg/day for males and 5, …

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High Background Incidence of Spontaneous Subcapsular Adrenal Gland Hyperplasia of Tg.rasH2 Mice Used in 26-week Carcinogenicity Studies

Molly H. Boyle, Madhav G. Paranjpe, Dianne M. Creasy

The Tg.rasH2 model was accepted by regulatory agencies worldwide for 26-week carcinogenicity assays as an alternative to the standard 2-year assays in conventional mice in 2003. Several references documenting spontaneous nonneoplastic findings and incidences of spontaneous tumors in the Tg.rasH2 mice have …

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Tg.rasH2 Mice and not CByB6F1 Mice Should Be Used for 28-Day Dose Range Finding Studies Prior to 26-Week Tg.rasH2 Carcinogenicity Studies

Madhav G. Paranjpe, Jessica L. Belich, Tom J. Vidmar, Reem H. Elbekai et autres

Our recent retrospective analysis of data, collected from 29 Tg.rasH2 mouse carcinogenicity studies, determined how successful the strategy of choosing the high dose for the 26-week studies was based on the estimated maximum tolerated dose (EMTD) derived from earlier 28-day dose range …

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Exudative Inflammatory Lesions in the Nasal Cavities of the 26-Week Tg.rasH2 Mice Oral Gavage Carcinogenicity Studies

Madhav G. Paranjpe, Jessica L. Belich, Dayauna R. Richardson, Tom J. Vidmar et autres

Three levels of nasal cavity sections (anterior, middle, and most posterior) are routinely examined as protocol required tissues in our 26-week carcinogenicity studies involving Tg.rasH2 mice. Exudative inflammation of the nasal cavity was noted in the most posterior section of both males …

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Progression of Serosal Vascular Proliferative Lesions to Hemangiosarcomas in the Uterus of the 26-Week Tg.rasH2 Mice Carcinogenicity Studies

Madhav G. Paranjpe, Jessica L. Belich, Dayauna R. Richardson, Tom J. Vidmar et autres

Tg.rasH2 mice are predisposed to hemangiosarcomas. Following the spleen, the uterus is the second most commonly affected organ in the female mice. Female mice are also predisposed to spontaneous vascular proliferative lesions on the serosal surface of the uterus, in which there …

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Renal Tumors in 26-Week Tg.Rash2 Mice Carcinogenicity Studies

Madhav G. Paranjpe, Jessica L. Belich, Marie E. McKeon, Reem H. Elbekai et autres

We report renal tubular adenomas and a carcinoma in 26-week Tg.rasH2 mouse carcinogenicity studies, which have not been reported to date either at our facility or in other published data. However, during the year 2014, renal tubular tumors were present in 4 …

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Regulatory Forum Opinion Piece*

Madhav G. Paranjpe, Melissa D. Denton, Tom J. Vidmar, Reem H. Elbekai

We recently conducted a retrospective analysis of data collected from 29 Tg.rasH2 carcinogenicity studies conducted at our facility to determine how successful was the strategy of choosing the high dose of the 26-week studies based on an estimated maximum tolerated dose (MTD). …

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