Abstract：
:Soman is a highly toxic organophosphorus chemical warfare compound that binds rapidly and irreversibility to a variety of serine active enzymes, i.e., butyryl- and acetyl-cholinesterases and carboxylesterase. The in vivo toxicity of soman has been reported to vary significantly in different animal species, such as rats and guinea pigs or non-human primates. This species variation makes it difficult to identify appropriate animal models for therapeutic drug development under the US Food and Drug Administration (FDA) Animal Rule. Since species variation in soman toxicity has been correlated with species variation in serum carboxylesterase, we undertook to determine if serum from guinea pigs, rats and non-human primates bound different levels of soman in vitro in the presence of equimolar concentrations of soman. Our results demonstrated that the amount of soman bound in the serum of rats was 4 uM, but essentially null in guinea pigs or non-human primates. The results strongly correlate with the presence or absence of carboxylesterase in the serum of animals and the difference in the toxic dose of soman in various species. Our results support prior suggestions that guinea pigs and non-human primates may be better animal models for the development of antidotes under the FDA Animal Rule.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Lenz DE,Cerasoli D,Maxwell DMdoi
10.1016/j.toxlet.2017.11.016subject
Has Abstractpub_date
2018-02-01 00:00:00pages
86-90eissn
0378-4274issn
1879-3169pii
S0378-4274(17)31475-3journal_volume
283pub_type
杂志文章abstract：:The effects of selenium on cellular toxicity and histochemical distribution of mercury were examined in a cell culture system of mouse peritoneal macrophages. Selenium protected against the toxicity of mercury in cultures exposed to 4 microM of mercuric chloride. Selenomethionine caused a significant increase in cell ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(89)90144-6
更新日期：1989-06-01 00:00:00
abstract：:Dermal toxicity of the new multi-insect repellent N,N-diethylphenylacetamide (DEPA) was studied in female rabbits. LD50 of DEPA was estimated to be 3505 mg/kg b.w. On daily topical application for 21 d at a dose of 50 mg/kg b.w., dermal irritancy score and blood chemistry changes indicated that the compound is non-irr...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(89)90160-4
更新日期：1989-01-01 00:00:00
abstract：:Troglitazone (Tro) is a thiazolidinedione antidiabetic drug that was withdrawn from the market due to its association with idiosyncratic severe liver injury. Tro has never induced liver injury in experimental animals in vivo. It was assumed that the species differences between human and experimental animals in the pha...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2012.08.001
更新日期：2012-10-02 00:00:00
abstract：:The widespread use of insecticides has amounted to a large scale 'experiment' in natural selection of insects by chemicals of toxicological importance to humans. Specific examples in which the molecular basis of insecticide resistance has been studied in detail are presented here. The biochemical/physiological mechani...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/0378-4274(95)03470-6
更新日期：1995-12-01 00:00:00
abstract：:One of the major side effects of aminoglycoside antibiotics (AG) is ototoxicity. The authors review the literature revealing many controversies on every aspect of this side-effect. Although epidemiological studies have to face the problem of reliable evaluation techniques, the incidence of cochleo- and vestibulotoxic ...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/0378-4274(90)90033-i
更新日期：1990-08-01 00:00:00
abstract：:Effects of intestinal damage on thyroid carcinogenesis due to amitrole (AT) were examined in F344 male rats initiated with N-bis(2-hydroxypropyl)nitrosamine (DHPN). In experiment 1, rats were provided with diet containing 0.03% AT for 20 weeks after a single subcutaneous injection of DHPN (2800 mg/kg body weight), and...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2005.11.012
更新日期：2006-06-20 00:00:00
abstract：:To test the toxicity of some substances, known to affect the nervous system i.e. organic solvents, heavy metals and DDT, their ability to cause cell detachment of cultured mouse neuroblastoma cells was investigated. A TD25 value was obtained by graphic estimation of the concentration needed to cause 25% of the total c...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(81)90024-2
更新日期：1981-10-01 00:00:00
abstract：:Eugenol, a natural phenolic constituent of clove oil, has a wide range of applications in medicine as a local antiseptic and anesthetic. However, the effect of eugenol on human glioblastoma is unclear. This study examined whether eugenol elevated intracellular free Ca(2+) levels ([Ca(2+)]i) and induced apoptosis in DB...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2014.10.023
更新日期：2015-01-05 00:00:00
abstract：:Chronic exposure of humans to fluorine compounds in the air, water and food may be atherogenic via the activation of oxidative stress and increased ROS production. The most important factor that promotes the formation of ROS seems to be the oxidoreduction of electron carriers in the critical points of the respiratory ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2010.03.1167
更新日期：2010-07-01 00:00:00
abstract：:CYP2E1 metabolizes 1,3-butadiene (BD) into genotoxic and possibly carcinogenic 1,2-epoxy-3-butene (EB), 1,2:3,4-diepoxybutane (DEB), and 1,2-epoxy-3,4-butanediol (EB-diol). The dose response of DNA and protein adducts derived from BD metabolites increases linearly at low BD exposures and then saturates at higher expos...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2013.08.025
更新日期：2013-11-25 00:00:00
abstract：:Tubule segments from defined stages of the mouse seminiferous epithelium were incubated for 4, 8 and 24 h in the presence of different concentrations of mono-2-ethylhexyl phthalate (MEHP), adriamycin, and N-ethyl-N-nitrosourea (ENU) to study the effects of these chemicals on germ cell apoptosis and DNA synthesis. Apop...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(03)00170-x
更新日期：2003-07-20 00:00:00
abstract：:Genomic DNA is under continuous assault by various chemical species produced by normal cellular metabolism. In addition, exposure to exogenous agents adds further insult. Modification of DNA by chemical carcinogens has long been recognized as an early event in carcinogenesis and many DNA adducts have been characterize...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/s0378-4274(02)00162-5
更新日期：2002-08-05 00:00:00
abstract：:A computer program (Q-test) was used to evaluate the combined toxic effects of nerve agent GF and its combined form with sarin (GB/GF) in mice. Efficacy of Jielin Injection, the 2-PAM-containing antidote used successfully in China for the treatment of organophosphate pesticide poisoning, was also evaluated and compare...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(97)00057-x
更新日期：1997-08-22 00:00:00
abstract：:Fluorocarbons containing chlorine or bromine have been associated with stratospheric ozone depletion and the search for suitable alternatives is progressing at an accelerated pace. The Program for Alternative Fluorocarbon Toxicity Testing (PAFT), an international group representing most of the world's CFC producers, h...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(93)90115-e
更新日期：1993-05-01 00:00:00
abstract：:Oral administration of a single dose of dibutyltin dilaurate (DBTL, 80 mg/kg body wt.), 2 or 24 h after treatment, caused no significant change in the levels of diacylglycerol and phosphoinositides in rat cerebrum (forebrain), whereas daily administration of DBTL (40 or 80 mg/kg body wt.) for 3 days (24 h after the fi...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(91)90198-f
更新日期：1991-08-01 00:00:00
abstract：:Recently published studies suggest a weak positive correlation between increased dietary acrylamide intake and the increased risk of endometrial and ovarian cancer. However, risk assessment of acrylamide remains difficult because the carcinogenic mechanisms are still unknown and in particular the molecular effects of ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2012.12.017
更新日期：2013-02-27 00:00:00
abstract：:This study demonstrates an intraspecies difference in elimination of methylmercury between two genetic variant strains of mice. Following a single non-toxic dose of 203Hg labeled methylmercury (0.5 mg Hg/kg i.p.), the half-time of 203Hg elimination in the CBA/J inbred strain was 7.4 days compared to 3.0 days in the CF...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(80)90114-9
更新日期：1980-10-01 00:00:00
abstract：:Clinical epidemiological studies have shown that there is a link between Parkinson's disease (PD) and cancer, but how PD regulates cancer development remains unknown. In our study, the effect of metabotropic glutamate receptor 5 (mGlu5) on hepatoma was explored in a rotenone-induced PD model both in vitro and in vivo....
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2018.02.019
更新日期：2018-05-15 00:00:00
abstract：:Iron is a unique poison because it is not a xenobiotic. It is an essential element and highly reactive. Because of the critical dependence upon iron and its potential to damage tissues, elaborate mechanisms have evolved for its efficient absorption, transport, cellular uptake, storage and conservation. These are incom...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(98)00279-3
更新日期：1998-12-28 00:00:00
abstract：:Manganese (Mn) is an essential trace element required for normal function and development. However, exposure to this metal at elevated levels may cause manganism, a progressive neurodegenerative disorder with neurological symptoms similar to idiopathic Parkinson's disease (IPD). Elevated body burdens of Mn from exposu...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2012.12.024
更新日期：2013-04-26 00:00:00
abstract：:Crotonaldehyde is an environment pollutant and lipid peroxidation product. Crotonaldehyde produces adverse effects to humans and serves as a risk factor for human pulmonary diseases. Like acrolein and 4-hydroxynonenal, crotonaldehyde seems likely to alter many cell signaling cascades, including inflammatory responses....
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2010.05.005
更新日期：2010-08-16 00:00:00
abstract：:The skin is highly sensitive to the chemical warfare agent in mustard gas, sulfur mustard (SM) that initiates a delayed injury response characterized by erythema, inflammation and severe vesication (blistering). Although SM poses a continuing threat, used as recently as in the Syrian conflict, no mechanism-based antid...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2018.03.007
更新日期：2018-09-01 00:00:00
abstract：:The chromosome damage induced by carboplatin (CBDCA) was evaluated in vitro. In human lymphocytes 5 micrograms/ml CBDCA produced a 7-fold increase in the frequency of sister chromatid exchanges (SCE) and a 3-fold increase in the number of cells with structural abnormalities compared with the control. Likewise, at this...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(94)03202-i
更新日期：1995-03-01 00:00:00
abstract：:We investigated the cytotoxic effects of formaldehyde (FA) on lymphocytes. FA-exposed mice showed a profound reduction not only in the number of natural killer (NK) cells but also in the expression of NK cell-specific receptors, but these mice did not exhibit decreases in the numbers of T or B lymphocytes. FA exposure...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2013.09.008
更新日期：2013-11-25 00:00:00
abstract：:Recent hypothesis suggesting a role for environmental toxins in the pathogenesis of neurodegenerative disorders has stimulated interest in research on xenobiotic metabolizing capability of the brain. In addition to possible irreversible loss of neurons through bioactivation in situ in the nervous tissue, the metabolis...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/0378-4274(95)03508-7
更新日期：1995-12-01 00:00:00
abstract：:Elevated urinary trehalase activity was observed in the inhabitants of the Jinzu River basin. Urinary trehalase activity was correlated with other urinalysis components, such as beta 2-microglobulin, glucose, amino nitrogen, and cadmium, of which a high level was observed in cadmium-polluted areas as compared with the...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(86)90206-7
更新日期：1986-12-01 00:00:00
abstract：:A major public health concern is the degree to which environmental or occupational exposures to exogenous chemicals result in adverse health effects. Biological markers have the potential for helping to answer this important question by providing links between markers of exposures and markers of early stages of the de...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/0378-4274(95)03569-9
更新日期：1995-12-01 00:00:00
abstract：:Cadmium specifically modify amine metabolism at the central nervous system and pituitary hormone secretions. Thus, the physiological functions controlled by these hormones can be modulated by cadmium. This xenobiotic is associated with deleterious effects on the gonadal function and with changes in the secretory patte...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/s0378-4274(99)00159-9
更新日期：1999-11-22 00:00:00
abstract：:The toxicity of diethylene glycol butyl ether (DGBE), and its principal metabolite, butoxyethoxyacetic acid (BEAA), were assessed in vitro for rat and human red blood cells. Rat erythrocytes showed evidence of mild hemolysis when exposed to BEAA at concentrations of 5 or 10 mM for 4 h. BEAA treated rat red blood cells...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2003.09.021
更新日期：2005-03-28 00:00:00
abstract：:Computer simulation can be used to integrate existing toxicity information within a biologically realistic framework. Simulation models calculate relevant measures of target tissue dose based on physiological, biochemical and physicochemical properties and readily support the dose, route, species and interchemical ext...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/0378-4274(89)90029-5
更新日期：1989-12-01 00:00:00
