NDLI: Hepatic transcriptomic alterations for N,N-dimethyl-p-toluidine (DMPT) and p-toluidine after 5-day exposure in rats

Content Provider	Springer Nature Link
Author	Dunnick, June K. Shockley, Keith R. Morgan, Daniel L. Brix, Amy Travlos, Gregory S. Gerrish, Kevin Michael Sanders, J. Ton, T. V. Pandiri, Arun R.
Copyright Year	2016
Abstract	N,N-dimethyl-p-toluidine (DMPT), an accelerant for methyl methacrylate monomers in medical devices, was a liver carcinogen in male and female F344/N rats and B6C3F1 mice in a 2-year oral exposure study. p-Toluidine, a structurally related chemical, was a liver carcinogen in mice but not in rats in an 18-month feed exposure study. In this current study, liver transcriptomic data were used to characterize mechanisms in DMPT and p-toluidine liver toxicity and for conducting benchmark dose (BMD) analysis. Male F344/N rats were exposed orally to DMPT or p-toluidine (0, 1, 6, 20, 60 or 120 mg/kg/day) for 5 days. The liver was examined for lesions and transcriptomic alterations. Both chemicals caused mild hepatic toxicity at 60 and 120 mg/kg and dose-related transcriptomic alterations in the liver. There were 511 liver transcripts differentially expressed for DMPT and 354 for p-toluidine at 120 mg/kg/day (false discovery rate threshold of 5 %). The liver transcriptomic alterations were characteristic of an anti-oxidative damage response (activation of the Nrf2 pathway) and hepatic toxicity. The top cellular processes in gene ontology (GO) categories altered in livers exposed to DMPT or p-toluidine were used for BMD calculations. The lower confidence bound benchmark doses for these chemicals were 2 mg/kg/day for DMPT and 7 mg/kg/day for p-toluidine. These studies show the promise of using 5-day target organ transcriptomic data to identify chemical-induced molecular changes that can serve as markers for preliminary toxicity risk assessment.
Starting Page	1685
Ending Page	1696
Page Count	12
File Format	PDF
ISSN	03405761
Journal	Archives of Toxicology
Volume Number	91
Issue Number	4
e-ISSN	14320738
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2016-09-16
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	N,N-dimethyl-p-toluidine p-Toluidine Liver toxicity Molecular markers Pharmacology/Toxicology Occupational Medicine/Industrial Medicine Environmental Health Biomedicine
Content Type	Text
Resource Type	Article
Subject	Health, Toxicology and Mutagenesis Medicine Toxicology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Pesticides: an update of human exposure and toxicity

Accelerated telomere shortening in peripheral blood lymphocytes after occupational polychlorinated biphenyls exposure

Toxicogenomic assessment of liver responses following subchronic exposure to furan in Fischer F344 rats

A 13-week nose-only inhalation toxicity study for perfluoro-n-butyl iodide (PFBI) in rats with recommended occupational exposure levels

Ameliorative effect of lycopene against 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced rat liver microsomal toxicity: an in vitro study.

Chronic Hepatic And Renal Toxicity By Cadmium In Rats

Predicting pulmonary fibrosis in humans after exposure to multi-walled carbon nanotubes (MWCNTs)

2,3,7,8 Tetrachlorodibenzo-p-dioxin-induced RNA abundance changes identify Ackr3, Col18a1, Cyb5a and Glud1 as candidate mediators of toxicity

Acute Hepatic Failure in a Dog after Xylitol Ingestion

Hepatic transcriptomic alterations for N,N-dimethyl-p-toluidine (DMPT) and p-toluidine after 5-day exposure in rats

Similar Documents

Pesticides: an update of human exposure and toxicity

Accelerated telomere shortening in peripheral blood lymphocytes after occupational polychlorinated biphenyls exposure

Toxicogenomic assessment of liver responses following subchronic exposure to furan in Fischer F344 rats

A 13-week nose-only inhalation toxicity study for perfluoro-n-butyl iodide (PFBI) in rats with recommended occupational exposure levels

Ameliorative effect of lycopene against 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced rat liver microsomal toxicity: an in vitro study.

Chronic Hepatic And Renal Toxicity By Cadmium In Rats

Predicting pulmonary fibrosis in humans after exposure to multi-walled carbon nanotubes (MWCNTs)

2,3,7,8 Tetrachlorodibenzo-p-dioxin-induced RNA abundance changes identify Ackr3, Col18a1, Cyb5a and Glud1 as candidate mediators of toxicity

Acute Hepatic Failure in a Dog after Xylitol Ingestion

Hepatic transcriptomic alterations for N,N-dimethyl-p-toluidine (DMPT) and p-toluidine after 5-day exposure in rats