Abstract:
:Chlorpyrifos (CPF) is a commonly used diethylphosphorothionate organophosphorus (OP) insecticide. Diethylphosphate (DEP), diethylthiophosphate (DETP) and 3,5,6-trichloro-2-pyridinol (TCPy) are products of both in vivo metabolism and environmental degradation of CPF and are routinely measured in urine as biomarkers of exposure. Hence, urinary biomonitoring of TCPy, DEP and DETP may be reflective of an individual's contact with both the parent pesticide and exposure to these metabolites in the environment. In the current study, simultaneous dosing of 13C- or 2H-isotopically labeled CPF (13C-labeled CPF, 5 13C on the TCPy ring; or 2H-labeled CPF, diethyl-D10 (deuterium labeled) on the side chain) were exploited to directly compare the pharmacokinetics and metabolism of CPF with TCPy, and DETP. The key objective in the current study was to quantitatively evaluate the pharmacokinetics of the individual metabolites relative to their formation following a dose of CPF. Individual metabolites were co-administered (oral gavage) with the parent compound at equal molar doses (14 micromol/kg; approximately 5 mg/kg CPF). Major differences in the pharmacokinetics between CPF and metabolite doses were observed within the first 3h of exposure, due to the required metabolism of CPF to initially form TCPy and DETP. Nonetheless, once a substantial amount of CPF has been metabolized (> or =3h post-dosing) pharmacokinetics for both treatment groups and metabolites were very comparable. Urinary excretion rates for orally administered TCPy and DETP relative to 13C-CPF or (2)H-CPF derived 13C-TCPy and 2H-DETP were consistent with blood pharmacokinetics, and the urinary clearance of metabolite dosed groups were comparable with the results for the 13C- and 2H-CPF groups. Since the pharmacokinetics of the individual metabolites were not modified by co-exposure to CPF; it suggests that environmental exposure to low dose mixtures of pesticides and metabolites will not impact their pharmacokinetics.
journal_name
Toxicologyjournal_title
Toxicologyauthors
Busby-Hjerpe AL,Campbell JA,Smith JN,Lee S,Poet TS,Barr DB,Timchalk Cdoi
10.1016/j.tox.2009.11.022subject
Has Abstractpub_date
2010-01-31 00:00:00pages
55-63issue
1-2eissn
0300-483Xissn
1879-3185pii
S0300-483X(09)00602-7journal_volume
268pub_type
杂志文章相关文献
TOXICOLOGY文献大全abstract::Leflunomide, used for the treatment of rheumatoid arthritis, has been reported to cause severe liver problems and liver failure; however, the underlying mechanisms are not clear. In this study, we used multiple approaches including genomic analysis to investigate and characterize the possible molecular mechanisms of t...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2017.10.002
更新日期:2017-12-01 00:00:00
abstract::Although the production of polychlorinated biphenyl 77 (PCB77) has already been banned globally, PCB77 is still used for a wide range of commercial purposes. Previous evidence has demonstrated that the PCB77 administration should be responsible for the gut microbiota variations and the host health risk. However, the h...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2019.03.011
更新日期:2019-05-15 00:00:00
abstract::The multiple cascades of signal transduction pathways that lead from receptors on the cell membrane to the nucleus, thus translating extracellular signals into changes in gene expression, may represent important targets for neurotoxic compounds. Among the biochemical steps and pathways that have been investigated are ...
journal_title:Toxicology
pub_type: 杂志文章,评审
doi:10.1016/s0300-483x(00)00435-2
更新日期:2001-03-07 00:00:00
abstract::We examined the effect of repeated ozone exposure on the respiratory system in mice, sensitized with ovalbumin (OA). OA-sensitized mice and saline-treated control mice were exposed to 1.0 ppm ozone or clean air for 6 h daily and five days weekly for five weeks. Subsequently, these mice were exposed to 1.0 ppm ozone fo...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2004.06.047
更新日期:2004-11-01 00:00:00
abstract::Presently, many consumer products contain nano-sized materials (NMs) to improve material properties, product quality and ease of use. NMs in food additives and in cosmetic articles (e.g., tooth paste) may be taken up by the oral route. As adverse effects of environmental nanoparticles, like ultrafine particles, have b...
journal_title:Toxicology
pub_type: 杂志文章,评审
doi:10.1016/j.tox.2011.11.004
更新日期:2012-01-27 00:00:00
abstract::Some effects of organophosphorus compounds (OPs) esters cannot be explained by action on currently recognized targets acetylcholinesterase or neuropathy target esterase (NTE). In previous studies, in membrane chicken brain fractions, four components (EPα, EPβ, EPγ and EPδ) of phenyl valerate esterase activity (PVase) ...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2018.08.018
更新日期:2018-12-01 00:00:00
abstract::The use of accurate and sensitive methods for the measurement of cytokines in body fluids is an absolute prerequisite for the proper use of these mediators in clinical practice. Many factors contribute to the complexity of cytokines quantitation: these molecules circulate at very low levels (e.g. pg/ml) under various ...
journal_title:Toxicology
pub_type: 杂志文章,评审
doi:10.1016/s0300-483x(98)00063-8
更新日期:1998-08-07 00:00:00
abstract::Recent Canadian research efforts have been directed towards the development of a reactive skin decontaminant (RSD) lotion active against classical nerve agents and mustard. The formulation presently under study consists of a 1.25 molal solution of potassium 2,3-butanedione monoximate (KBDO) in polyethylene glycol meth...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(91)90028-y
更新日期:1991-05-01 00:00:00
abstract::The cytotoxicity and cardiotoxicity of benzoyl mustard (FCE 24517) and epoxamido (FCE 24561) synthetic derivatives of distamycin A were reported in the present study. The 50% inhibiting concentration (IC50) of colony formation of FCE 24517 on human SNB-19 glioblastoma, A2780 ovarian cancer and DU 145 prostate cancer w...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(92)90003-w
更新日期:1992-11-15 00:00:00
abstract::The cytotoxicity of CdCl2 and 2 isoforms of hepatic cadmium-metallothionein (CdMT I and II), was investigated using primary cultures of rat hepatocytes. The cell cultures were exposed to cadmium as CdCl2 or as either isoform of CdMT for a 20-h period at concentrations ranging from 50 to 500 ng Cd X ml-1. Cytotoxicity ...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(87)90034-5
更新日期:1987-06-01 00:00:00
abstract::In our experiments on acutely lead exposed rats we observed a marked increase (a 2-fold or 3-fold increase with 30 mg/kg or 60 mg/kg lead acetate, respectively) in [3H]quinuclidinyl benzilate [( 3H]QNB) specific binding to muscarine receptors from striatum and cortex, without any change in receptor affinity. Muscarine...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(84)90005-2
更新日期:1984-05-14 00:00:00
abstract::To establish a paraquat-resistant Wistar rat strain, we carried out continuous sister-brother mating among rats that survived high-dose intraperitoneal administration of paraquat dichloride (360 mg/kg). The percentages of paraquat-resistant rats among wild rats and among the fifth-generations were 7.1% and 20.6%, resp...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(00)00299-7
更新日期:2000-11-23 00:00:00
abstract::Haptens are classified as low molecular chemicals with an intrinsic potential to covalently modify proteins, and many of them are strong inducers of contact hypersensitivity (CHS). CHS is T cell mediated, and hapten-specific T cells have been shown to interact with hapten-modified, MHC-associated peptides. However, th...
journal_title:Toxicology
pub_type: 杂志文章,评审
doi:10.1016/j.tox.2004.12.015
更新日期:2005-04-15 00:00:00
abstract::There are reports of alterations in the number and functions of the cells of the immune system in patients with metal-on-metal (MOM) orthopaedic implants. These effects have been correlated with elevated chromium levels in the patients' blood. We have investigated the interactions of clinically relevant concentrations...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2007.04.002
更新日期:2007-07-01 00:00:00
abstract::Excretion and organ distribution of mercury and susceptibility to methylmercury (MeHg) toxicity were compared between strains and sexes after successive oral administration of MeHg chloride (5 mg/kg per day) using BALB/cA (C) and C57BL/6N (B6) mice. Every mouse died several days after initiation of toxic symptoms, and...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(88)90079-0
更新日期:1988-09-01 00:00:00
abstract::The sulphur and nitrogen mustards are strong alkylating agents, which induces inflammations of the skin including blistering right up to ulcerations. Depending on the severity, the wounds may need weeks to heal. In the past it was shown that sulphur mustard has a destructive effect on endothelial precursor cells, whic...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2008.09.015
更新日期:2009-09-01 00:00:00
abstract::The use of colchicine-specific Fab fragments is of interest in human poisoning. In the present study, we show the efficacy of Fab fragments in reversing colchicine toxicity in mice. High affinity antibodies (Ka = 2 x 10(10) M-1) against colchicine were raised in goats; Fab fragments were purified by DEAE chromatograph...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(91)90015-s
更新日期:1991-01-01 00:00:00
abstract::Ethyl tertiary butyl ether (ETBE) is biofuel additive recently used in Japan and some other countries. Limited evidence shows that ETBE has low toxicity. Acetaldehyde (AA), however, as one primary metabolite of ETBE, is clearly genotoxic and has been considered to be a potential carcinogen. The aim of this study was t...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2013.06.005
更新日期:2013-09-15 00:00:00
abstract::Phensuximide (PSX) is an antiepileptic agent which has been shown to induce hemorrhagic cystitis and mild nephrotoxicity following repeated administration in man or rats or when acutely administered to phenobarbital-pretreated rats. The purpose of this study was to explore the role of para-hydroxylation of the phenyl ...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(92)90045-g
更新日期:1992-08-01 00:00:00
abstract::The present study investigates the influence of different levels of Schistosoma mansoni infection (60, 120, 180, 300, 600 cercariae per mice) after 33 days on the activity of aryl hydrocarbon hydroxylase (AHH) and the formation of hepatic hydrogen peroxide (H(2)O(2)) during the metabolic activation of benzo(a)pyrene [...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(01)00372-9
更新日期:2001-06-21 00:00:00
abstract::For half of the 30-odd years that diacetyl-exposed workers have developed disabling lung disease, obliterative bronchiolitis was unrecognized as an occupational risk. Delays in its recognition as an occupational lung disease are attributable to the absence of a work-related temporal pattern of symptoms; failure to rec...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2016.06.009
更新日期:2017-08-01 00:00:00
abstract::Flucloxacillin is a semi-synthetic penicillin widely used in the prophylaxis and treatment of staphylococcal infections. Severe liver reactions, characterised by delayed cholestatic hepatitis and a prolonged course of recovery, are associated with flucloxacillin therapy. Clinical findings are suggestive of an immune m...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2005.07.015
更新日期:2005-12-01 00:00:00
abstract::The objective of this study was to compare the disposition and metabolism of [14C]1,2-dichloropropane [( 14C]DCP) following oral and inhalation exposure since these two routes are of interest with regards to occupational and accidental exposure. [14C]DCP was administered orally to groups of four rats of each sex as a ...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(91)90076-d
更新日期:1991-01-01 00:00:00
abstract::Several studies indicated that chloral hydrate can prolong the disappearance time of ethanol from blood in mice. This seems to result from inhibition of the enzyme alcohol dehydrogenase by chloral hydrate and trichloroethanol, its main metabolite. We examined the effect of both these compounds on the disappearance tim...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(98)00108-5
更新日期:1998-11-02 00:00:00
abstract::The effect of zinc (Zn) on the immunomodulatory properties of cadmium (Cd) was investigated in male Wistar rats. Animals were orally exposed to Cd and or Zn, by stomach tubing for 7 weeks. Response of splenocytes to phytohemagglutinin (PHA) and concanavalin A (Con A), was significantly increased by Zn. When exposed in...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(84)90046-5
更新日期:1984-12-01 00:00:00
abstract::We compared the results of the multiple-dose guinea pig maximization test (GPMT) and the non-radioactive murine local lymph-node assay (LLNA) for various biocides. Thirteen out of 17 positive biocides in the GPMT gave positive results in the LLNA. In the GPMT, the minimum first induction doses ranged over four orders ...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2005.02.014
更新日期:2005-07-01 00:00:00
abstract::Silver nanoparticles (AgNPs) are widely utilized in various consumer products and medical devices, especially due to their antimicrobial properties. However, several studies have associated these particles with toxic effects, such as inflammation and oxidative stress in vivo and cytotoxic and genotoxic effects in vitr...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2012.09.014
更新日期:2013-11-08 00:00:00
abstract::Inhibition of fungal lanosterol-14 alpha-demethylase (CYP51) is the working principle of the antifungal activity of azoles used in agriculture and medicine. Inhibition of human CYP51 may result in endocrine disruption since follicular fluid-meiosis activating steroid (FF-MAS), the direct product of lanosterol demethyl...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2006.08.007
更新日期:2006-11-10 00:00:00
abstract::A fixed combination of the three components, fructose, cyclosporin A and trifluoperazine (FCAT), was found to protect in the late stage of paracetamol-induced liver cell injury both in vivo and in an in vivo/in vitro system. Rats pre-induced with phenobarbitone were given a paracetamol dose of 1 g/kg i.p. The combinat...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(95)03262-e
更新日期:1996-03-18 00:00:00
abstract::In the clinical setting, antidotes are generally administered after the occurrence of a drug overdose. Therefore, the most pertinent evaluation of any new agent should model human exposure. This study tested whether acetaminophen (APAP) hepatotoxicity was reversed when S-adenosyl-L-methionine (SAMe) was administered a...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2007.10.027
更新日期:2008-02-03 00:00:00