Abstract:
:Isoprene (2-methyl-1,3-butadiene), a volatile monomer occurring in the natural environment and used in the manufacture of elastomers, is a close chemical relative of the animal carcinogen 1,3-butadiene. To obtain toxicokinetic data for inhaled isoprene, male F344 rats were exposed in groups of 30 to 14C-labeled isoprene vapor at four concentrations from 8 to 8200 ppm. The percentage of the inhaled isoprene that was metabolized decreased with increasing exposure concentration. The percentage of the total metabolites (that is, non-isoprene-retained 14C) excreted in urine and feces or expired was determined as a function of vapor concentration. About 75% of the total metabolites was excreted in urine. This was independent of inhaled isoprene concentration. After exposure to 8200 ppm, a larger percentage of the metabolites was excreted in feces than after exposure to lower concentrations. Using vacuum line techniques, blood metabolite concentrations were determined as functions of both vapor concentration and exposure duration. At one exposure concentration (1480 ppm) metabolites were measured in the nose, lungs, liver, kidney, and fat, as well as in blood. A mutagenic metabolite, isoprene diepoxide, was tentatively identified in all tissues examined. Between 0.0018 and 0.031% of the inhaled 14C label was tentatively identified as this metabolite in blood. The relative amount of the metabolites present in blood was highest for low concentrations of inhaled isoprene and for shorter exposure durations. Body fat appeared to be a reservoir for both isoprene metabolites and isoprene itself. The appearance of metabolites in the respiratory tract after short exposure durations together with low blood concentrations of isoprene indicated that substantial metabolism of inhaled isoprene in the respiratory tract may occur.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Dahl AR,Birnbaum LS,Bond JA,Gervasi PG,Henderson RFdoi
10.1016/0041-008x(87)90044-5subject
Has Abstractpub_date
1987-06-30 00:00:00pages
237-48issue
2eissn
0041-008Xissn
1096-0333journal_volume
89pub_type
杂志文章abstract::The metabolism of CCl(4) initiates the peroxidation of polyunsaturated fatty acids producing alpha,beta-unsaturated aldehydes, such as 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA). The facile reactivity of these electrophilic aldehydic products suggests they play a role in the toxicity of compounds like CCl(4). ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1999.8788
更新日期:1999-11-15 00:00:00
abstract::Copper (II) complexes are promising in the development of new synthetic models for cancer treatment. In this context, we synthesized a new copper complex containing the pharmacophore group 1,4-dioxo-2-butenyl, the Bis(((Z)-4-((4-chlorophenyl) amino)-4-oxobut-2-enoyl)oxy) copper compound and we evaluated its antitumor ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2018.08.004
更新日期:2018-10-01 00:00:00
abstract::The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor which plays a role in the development of multiple tissues and is activated by a large number of ligands, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In order to examine the roles of the AHR in both normal biological development an...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2013.06.024
更新日期:2013-10-15 00:00:00
abstract::Previous studies performed in this laboratory have shown that certain benzo(a)pyrene (BaP) metabolites, such as benzo(a)pyrene-7,8-dihydrodiol (BaP-7,8-diol) and benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), were more effective in elevating intracellular Ca2+ in normal human peripheral blood mononuclear cell (HP...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1997.8345
更新日期:1998-03-01 00:00:00
abstract::Hepatic expression of the proinflammatory cytokine tumor necrosis factor-alpha (TNFalpha) occurs in many acute and chronic liver diseases, as well as following exposure to hepatotoxic chemicals, and is believed to help influence both the damage and repair processes that occur following these insults by regulating addi...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.2001.9304
更新日期:2001-12-01 00:00:00
abstract::Hydrolytic metabolism of pyrethroid insecticides in humans is one of the major catabolic pathways that clear these compounds from the body. Rodent models are often used to determine the disposition and clearance rates of these esterified compounds. In this study the distribution and activities of esterases that cataly...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2007.03.002
更新日期:2007-05-15 00:00:00
abstract::Arsenic is a toxicant found in ground water around the world, and human exposure mainly comes from drinking water or from crops grown in areas containing arsenic in soils or water. Epidemiological studies have shown that arsenic exposure during development decreased intellectual function, reduced birth weight, and alt...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2014.10.007
更新日期:2014-12-15 00:00:00
abstract::We developed a fusion toxin consisting of the catalytic and translocation domains of diphtheria toxin linked to human granulocyte-macrophage colony-stimulating factor (GM-CSF) (DTGM) for the treatment of patients with acute myeloid leukemia (AML). Our goal in this study was to determine the toxicity and pharmacokineti...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1999.8691
更新日期:1999-07-15 00:00:00
abstract::4-Alkylbicyclophosphates, R1C(CH2O)3P(O), with suitable R1 substituents (e.g., t-butyl, isopropyl, or cyclohexyl) are highly toxic compounds [mouse intraperitoneal (ip) LD50 values 0.036-0.52 mg/kg] and are potent noncompetitive gamma-aminobutyric acid (GABA) antagonists. 4-Alkylmonocyclophosphates of the type R1(HOCH...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(85)90119-x
更新日期:1985-10-01 00:00:00
abstract::Many cationic drugs are concentrated in acidic cell compartments due to low retro-diffusion of the protonated molecule (ion trapping), with an ensuing vacuolar and autophagic cytopathology. In solid tissues, there is evidence that phagocytic cells, e.g., histiocytes, preferentially concentrate cationic drugs. We hypot...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2013.04.004
更新日期:2013-07-15 00:00:00
abstract::Geogenic dust from arid environments is a possible inhalation hazard for humans, especially when using off-road vehicles that generate significant dust. This study focused on immunotoxicological and neurotoxicological effects following subacute exposure to geogenic dust generated from sediments in the Nellis Dunes Rec...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2016.05.017
更新日期:2016-08-01 00:00:00
abstract::A BLU:Ha newborn mouse lung adenoma bioassay was employed to compare the tumorigenicity of selected mononitroarenes and unsubstituted parent compounds 6 months after initial treatment. The presence of a nitro group had a variable effect upon compound potency in which tumorigenicity was increased, abolished, or unchang...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(89)90162-2
更新日期:1989-07-01 00:00:00
abstract::Renal glutathione (GSH) concentrations were reduced approximately 80% at 4 hr after a single injection of buthionine sulfoxime (BSO) (4 mmol/kg body wt) and remained reduced for at least 16 hr in male rats. Following BSO injection, rats were injected with a nephrotoxic dose of cadmium-metallothionein (Cd-MT) (0.3 mg C...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(89)90182-8
更新日期:1989-05-01 00:00:00
abstract::Organophosphorus-ester induced delayed neurotoxicity (OPIDN) is a neurodegenerative disorder characterized by ataxia progressing to paralysis with a concomitant central and peripheral, distal axonapathy. Diisopropylphosphorofluoridate (DFP) produces OPIDN in the chicken that results in mild ataxia in 7-14 days and sev...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2011.07.017
更新日期:2011-11-01 00:00:00
abstract::We investigated the role of air humidity and allergic sensitization on the acute airway response to inhaled formaldehyde (FA) vapor. Mice were sensitized to the immunogen ovalbumin (OVA) by three intraperitoneal injections followed by two aerosol challenges, giving rise to allergic airway inflammation. Control mice we...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2013.02.006
更新日期:2013-05-01 00:00:00
abstract::Acrolein is a highly toxic, volatile, unsaturated aldehyde generated during incomplete combustion as in tobacco smoke and indoor fires. Because the transient receptor potential ankyrin 1 (TRPA1) channel mediates tobacco smoke-induced lung injury, we assessed its role in high-level acrolein-induced toxicity in mice. Ac...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2016.08.028
更新日期:2017-06-01 00:00:00
abstract::Defects in tryptophan metabolism on the l-kynurenine pathway (KP) are implicated in a number of human diseases, including chronic kidney disease, brain edema or injury, tuberculosis and malaria - as well as cancer, neurodegenerative and autoimmune disorders. However, it is unclear to what extent detrimental effects of...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2018.01.004
更新日期:2018-02-15 00:00:00
abstract::Phenobarbital (PB) is an effective growth stimulator of hepatic hyperplastic nodules developed with diethylnitrosamine and 2-acetylaminofluorene plus partial hepatectomy (the Solt-Farber model), but it does not apparently stimulate the growth of preneoplastic lesions produced with aflatoxin B1 (AFB). Some studies have...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(91)90142-2
更新日期:1991-10-01 00:00:00
abstract::Erionite, a naturally occurring fibrous zeolite, is associated with the development of nonmalignant and malignant lung diseases and is more carcinogenic than asbestos fibers in man and rodent inhalation models of disease. To investigate the possible molecular mechanisms of erionite-induced toxicity and carcinogenesis ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1998.8450
更新日期:1998-07-01 00:00:00
abstract::A physiologically based model of lead absorption and disposition, previously developed and validated for adults, has been tested and calibrated for children. The model was modified to incorporate additional information on the age dependence of bone formation rate and to take into account increasing localization of bon...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章,评审
doi:10.1006/taap.1995.1072
更新日期:1995-04-01 00:00:00
abstract::Cadmium chloride (CdCl2) at a dose of 1 mg/kg of body weight was injected into male Wistar rats twice a day (12-hr intervals) for 7 consecutive days. A group of treated rats was maintained without any treatment for an additional period of 10 days and killed on the following day (on Day 18). Plasma aldosterone concentr...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(84)90346-6
更新日期:1984-12-01 00:00:00
abstract::Melatonin is a modified tryptophan with potent biological activity, exerted by stimulation of specific plasma membrane (MT1/MT2) receptors, by lower affinity intracellular enzymatic targets (quinone reductase, calmodulin), or through its strong anti-oxidant ability. Scattered studies also report a perplexing pro-oxida...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2009.05.012
更新日期:2009-08-15 00:00:00
abstract::Voriconazole is one of the most frequently used antifungal drugs for the initial treatment of invasive aspergillosis, but liver-related adverse events occur frequently and usually lead to drug discontinuation. Moreover, the mechanism of voriconazole-induced hepatotoxicity remains unsettled. A holistic understanding of...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2020.115157
更新日期:2020-09-15 00:00:00
abstract::Pulmonary responses after continuous exposure of rats to concentrations of ozone (O3) ranging from 0.12 to 0.64 ppm were quantified by measuring tissue collagen synthesis rate, tissue protein and DNA content, and various constituents of bronchoalveolar lavage fluid. After 7 days of exposure to 0.64 ppm of O3, lung col...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(86)90252-8
更新日期:1986-07-01 00:00:00
abstract::The vitamin E analogue alpha-tocopheryl succinate (alpha-TOS) is an efficient anti-cancer drug. Improved efficacy was achieved through the synthesis of alpha-tocopheryl maleamide (alpha-TAM), an esterase-resistant analogue of alpha-tocopheryl maleate. In vitro tests demonstrated significantly higher cytotoxicity of al...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2009.01.027
更新日期:2009-06-15 00:00:00
abstract::Nucleoside analog reverse transcriptase inhibitors (NRTIs) are known to directly inhibit mitochondrial complex I activity as well as various mitochondrial kinases. Recent observations that complex I activity and superoxide production are modulated through cAMP-dependent phosphorylation suggests a mechanism through whi...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2007.08.015
更新日期:2008-01-01 00:00:00
abstract::Gastric cancer ranks as the third leading cause of cancer-related death worldwide. The uncontrolled tumor growth and robust metastasis are key factors to cause the cancer patient death. Mechanistically, aberrant activation of Notch and NF-κB signaling pathways plays pivotal roles in the initiation and metastasis of ga...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2019.114870
更新日期:2020-02-01 00:00:00
abstract::St. John's wort (SJW, Hypericum perforatum) is one of the popular nutraceuticals for treating depression. Methotrexate (MTX) is an immunosuppressant with narrow therapeutic window. This study investigated the effect of SJW on MTX pharmacokinetics in rats. Rats were orally given MTX alone and coadministered with 300 an...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2012.05.020
更新日期:2012-08-15 00:00:00
abstract::Acetaminophen (APAP) and 7-hydroxy-2-acetylaminofluorene (7-OH-AAF) each produced a similar incidence of, as well as a qualitatively similar, abnormal closure of the anterior neuropore at similar concentrations when added to the medium of cultured rat embryos. At concentrations producing a 50-65% incidence of abnormal...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(89)90260-3
更新日期:1989-03-01 00:00:00
abstract::To study the effect of cadmium exposure on maternal and fetal zinc metabolism, rats were exposed to 0, 5, 50, or 100 ppm Cd in the drinking water on Days 6 through 20 of pregnancy. In comparison to controls, fetal and maternal weights were slightly reduced in the 50- and 100-ppm groups, but not the 5-ppm group. Multip...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(90)90048-y
更新日期:1990-03-01 00:00:00