Evidence-based toxicology: a comprehensive framework for causation

PS Guzelian, MS Victoroff, NC Halmes… - Human & …, 2005 - journals.sagepub.com
This paper identifies deficiencies in some current practices of causation and risk evaluation
by toxicologists and formulates an evidence-based solution. The practice of toxicology …

Protein targets of xenobiotic reactive intermediates

NR Pumford and, NC Halmes - Annual review of pharmacology …, 1997 - annualreviews.org
▪ Abstract Many xenobiotics are metabolically activated to electrophilic intermediates that form
covalent adducts with proteins; the mechanism of toxicity is either intrinsic or idiosyncratic …

Immunochemical detection of oxidized proteins

RJ Keller, NC Halmes, JA Hinson… - Chemical research in …, 1993 - ACS Publications
An immunochemical assay was developed to detect carbonyl moieties that result from
oxidative damage to proteins. Bovine serum albumin was reacted with hydroxyl radicals …

Covalent binding of xenobiotics to specific proteins in the liver

NR Pumford, NC Halmes, JA Hinson - Drug metabolism reviews, 1997 - Taylor & Francis
The toxicity of many drugs and environmental chemicals requires metabolic activation, primarily
through the cytochrome P450 system, to reactive intermediates which bind covalently to …

Glutamate dehydrogenase covalently binds to a reactive metabolite of acetaminophen

NC Halmes, JA Hinson, BM Martin… - Chemical research in …, 1996 - ACS Publications
The mechanism of the hepatotoxicity of the analgesic acetaminophen is believed to be
mediated by covalent binding to protein; however, critical targets which effect the toxicity are …

Covalent binding of acetaminophen to N-10-formyl-tetrahydrofolate dehydrogenase in mice

NR Pumford, NC Halmes, BM Martin, RJ Cook… - … of Pharmacology and …, 1997 - ASPET
The analgesic acetaminophen is frequently used as a model chemical to study hepatotoxicity;
however, the critical mechanisms by which it produces toxicity within the cell are unknown. …

Immunochemical detection of protein adducts in mice treated with trichloroethylene

NC Halmes, DC McMillan, JE Oatis… - Chemical research in …, 1996 - ACS Publications
Trichloroethylene has been shown to produce tumors in rodents and is a suspect human
carcinogen. In addition, a number of case reports raise the possibility that trichloroethylene can …

Reevaluating cancer risk estimates for short-term exposure scenarios

NC Halmes, SM Roberts, JK Tolson… - Toxicological …, 2000 - academic.oup.com
Estimates of cancer risk from short-term exposure to carcinogens generally rely on cancer
potency values derived from chronic, lifetime-exposure studies and assume that exposures of …

The acetaminophen regioisomer 3′-hydroxyacetanilide inhibits and covalently binds to cytochrome P450 2E1

NC Halmes, VM Samokyszyn, TW Hinton, JA Hinson… - Toxicology letters, 1998 - Elsevier
3′-Hydroxyacetanilide has been previously studied as a nontoxic regioisomer of the analgesic
acetaminophen (4′-hydroxyacetanilide). The radiolabeled derivative has been shown …

Detection of trichloroethylene-protein adducts in rat liver and plasma

NC Halmes, EJ Perkins, DC McMillan, NR Pumford - Toxicology letters, 1997 - Elsevier
Trichloroethylene is an industrial chemical with widespread occupational exposure and is a
major environmental contaminant. In a Western blot using antiserum that recognizes …