A comparative 90-day toxicity study of allyl acetate, allyl alcohol and acrolein.

Abstract:

:Allyl acetate (AAC), allyl alcohol (AAL), and acrolein (ACR) are used in the manufacture of detergents, plastics, pharmaceuticals, and chemicals and as agricultural agents. A metabolic relationship exists between these chemicals in which allyl acetate is metabolized to allyl alcohol and subsequently to the highly reactive, alpha,beta-unsaturated aldehyde, acrolein. Due to the weaker reactivity of the protoxicants, allyl acetate and allyl alcohol, relative to acrolien we hypothesized the protoxicants would attain greater systemic exposure and therefore deliver higher doses of acrolein to the internal organs. By extension, the higher systemic exposure to acrolein we hypothesized should lead to more internal organ toxicity in the allyl acetate and allyl alcohol treated animals relative to those treated with acrolein. To address our hypothesis we compared the range of toxicities produced by all three chemicals in male and female Fischer 344/N rats and B6C3F1 mice exposed 5 days a week for 3 months by gavage in 0.5% methylcellulose. Rats (10/group) were dosed with 0-100mg/kg allyl acetate, 0-25mg/kg allyl alcohol, or 0-10mg/kg acrolein. Mice (10/group) were dosed with 0-125mg/kg allyl acetate, 0-50mg/kg allyl alcohol, or 0-20mg/kg acrolein. The highest dose of allyl acetate and acrolein decreased survival in both mice and rats. The primary target organ for the toxicity of all three chemicals in both species and sexes was the forestomach; squamous epithelial hyperplasia was observed following exposure to each chemical. In both species the highest allyl acetate dose group exhibited forestomach epithelium necrosis and hemorrhage and the highest dose of acrolein led to glandular stomach hemorrhage. Liver histopathology was the most apparent with allyl acetate, was also observed with allyl alcohol, but was not observed with acrolein. All chemicals had effects on the hematopoietic system with allyl acetate having the most pronounced effect. When dosed at quantities limited by toxicity, allyl acetate and allyl alcohol produce higher levels of urinary mercapturic acids than the minimally toxic dose of acrolein. This observation is likely due to biotransformation of allyl acetate and ally alcohol to acrolein that occurs after absorption and suggests that these chemicals are protoxicants that increase systemic exposure of acrolein. Increased systemic exposure to acrolein is likely responsible for the differences in hepatic toxicological profile observed with these chemicals.

journal_name

Toxicology

journal_title

Toxicology

authors

Auerbach SS,Mahler J,Travlos GS,Irwin RD

doi

10.1016/j.tox.2008.08.014

subject

Has Abstract

pub_date

2008-11-20 00:00:00

pages

79-88

issue

1-3

eissn

0300-483X

issn

1879-3185

pii

S0300-483X(08)00417-4

journal_volume

253

pub_type

杂志文章
  • The modulation by metallothionein of cadmium-induced cytotoxicity in primary hepatocyte cultures.

    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

    authors: Beattie JH,Marion M,Denizeau F

    更新日期:1987-06-01 00:00:00

  • Effects of drug-metabolizing enzyme inducers on cephaloridine toxicity in Fischer 344 rats.

    abstract::High doses of cephaloridine produce necrosis of renal proximal tubular cells and this nephrotoxicity has been shown to be reduced by piperonyl butoxide (a mixed-function oxidase inhibitor) in rats and rabbits, and potentiated by phenobarbital (a mixed-function oxidase inducer) in rabbits but not rats. Phenobarbital is...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/0300-483x(82)90011-7

    authors: Kuo CH,Hook JB

    更新日期:1982-01-01 00:00:00

  • The cytolytic toxin aerolysin: from the soluble form to the transmembrane channel.

    abstract::Aerolysin is a cytolytic toxin which forms channels in the plasma membranes of eucaryotic cells. The protein is secreted by Aeromonas hydrophila as an inactive protoxin. Its stability and water solubility are conferred by its ability to dimerize. Maturation of the protein occurs through proteolytic removal of a C-term...

    journal_title:Toxicology

    pub_type: 杂志文章,评审

    doi:10.1016/0300-483x(94)90152-x

    authors: van der Goot FG,Pattus F,Parker M,Buckley JT

    更新日期:1994-02-28 00:00:00

  • Study of the protective effect of ascorbic acid against the toxicity of stannous chloride on oxidative damage, antioxidant enzymes and biochemical parameters in rabbits.

    abstract::Stannous chloride (SnCl2) is a reducing chemical agent used in several man-made products. SnCl2 can generate reactive oxygen species (ROS). Therefore, the present study has been carried out to investigate the antioxidant action of l-ascorbic acid (AA) in minimizing SnCl2 toxicity on lipid peroxidation, antioxidant enz...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/j.tox.2007.03.017

    authors: Yousef MI,Awad TI,Elhag FA,Khaled FA

    更新日期:2007-06-25 00:00:00

  • The interactions of cis-diamminedichloroplatinum with metallothionein and glutathione in rat liver and kidney.

    abstract::The involvement of metallothionein (MT) in the nephrotoxicity of cis-diamminedichloroplatinum (c-DDP) was investigated in rats using enzyme excretion and histology as indicators of renal damage. In addition, the effects of renal glutathione (GSH) depletion on the nephrotoxicity of c-DDP was assessed by organic anion t...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/0300-483x(90)90129-5

    authors: Suzuki CA,Cherian MG

    更新日期:1990-11-01 00:00:00

  • Cadmium impairs the survival and proliferation of cultured adult subventricular neural stem cells through activation of the JNK and p38 MAP kinases.

    abstract::Cadmium (Cd) is a heavy metal with a long biological half-life in humans and is recognized as a toxic pollutant. Cd is also a potential neurotoxicant and its exposure is associated with olfactory impairment in humans. However, the molecular and cellular mechanisms of Cd neurotoxicity are not well defined. Adult neurog...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/j.tox.2017.01.013

    authors: Wang H,Engstrom AK,Xia Z

    更新日期:2017-04-01 00:00:00

  • Anthraquinone-induced cell injury: acute toxicity of carminomycin, epirubicin, idarubicin and mitoxantrone in isolated cardiomyocytes.

    abstract::Acute toxic effects of the antineoplastic anthraquinones carminomycin, epirubicin, idarubicin and mitoxantrone were studied in primary cultures of cardiomyocytes, which were isolated from adult rats. Both time- and concentration-dependent changes of cell structure and viability (trypan blue exclusion) following incuba...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/s0300-483x(99)00041-4

    authors: Andersson BS,Eksborg S,Vidal RF,Sundberg M,Carlberg M

    更新日期:1999-07-01 00:00:00

  • Methylmercury exposure causes a persistent inhibition of myogenin expression and C2C12 myoblast differentiation.

    abstract::Methylmercury (MeHg) is a ubiquitous environmental toxicant, best known for its selective targeting of the developing nervous system. MeHg exposure has been shown to cause motor deficits such as impaired gait and coordination, muscle weakness, and muscle atrophy, which have been associated with disruption of motor neu...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/j.tox.2017.11.002

    authors: Prince LM,Rand MD

    更新日期:2018-01-15 00:00:00

  • Different levels of Schistosoma mansoni infection increased the mutagenicity of benzo(a)pyrene, the activity of aryl hydrocarbon hydroxylase and the formation of hepatic microsomal hydrogen peroxide.

    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

    authors: Awney HA,Ghzlan HE,Sheweita SA,Mostafa MH

    更新日期:2001-06-21 00:00:00

  • Metabolic activity testing can underestimate acute drug cytotoxicity as revealed by HepG2 cell clones overexpressing cytochrome P450 2C19 and 3A4.

    abstract::Preclinical drug safety assessment includes in vitro studies with physiologically relevant cell cultures. As an in vitro system for hepatic toxicology testing, we have been generating cell clones of human hepatoblastoma cell line HepG2 by lentiviral transduction of phase I cytochrome P450 (CYP) enzymes. Here, we prese...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/j.tox.2018.11.008

    authors: Steinbrecht S,König R,Schmidtke KU,Herzog N,Scheibner K,Krüger-Genge A,Jung F,Kammerer S,Küpper JH

    更新日期:2019-01-15 00:00:00

  • NLRC5 promotes cell proliferation via regulating the AKT/VEGF-A signaling pathway in hepatocellular carcinoma.

    abstract::NLRC5, a newly found member of the NLR family and the largest member of nucleotide-binding, has been reported to regulate immune responses and is associated with hepatocellular carcinoma (HCC). We investigated the mechanisms and signaling pathways of NLRC5 in HCC progression. Increased expression of NLRC5, vascular en...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/j.tox.2016.06.012

    authors: He YH,Li MF,Zhang XY,Meng XM,Huang C,Li J

    更新日期:2016-06-01 00:00:00

  • Chemical mixtures: challenge for toxicology and risk assessment.

    abstract::It is now well-recognized that human environmental exposures are not to single chemicals. Rather, humans are exposed, either concurrently or sequentially, to multiple chemicals. Challenges that chemical mixtures pose for risk assessment and toxicology are presented. Challenge areas include increasing the peer-reviewed...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/0300-483x(95)03205-t

    authors: Simmons JE

    更新日期:1995-12-28 00:00:00

  • Sodium valproate induces mitochondrial respiration dysfunction in HepG2 in vitro cell model.

    abstract::Sodium valproate (VPA) is a potentially hepatotoxic antiepileptic drug. Risk of VPA-induced hepatotoxicity is increased in patients with mitochondrial diseases and especially in patients with POLG1 gene mutations. We used a HepG2 cell in vitro model to investigate the effect of VPA on mitochondrial activity. Cells wer...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/j.tox.2015.03.001

    authors: Komulainen T,Lodge T,Hinttala R,Bolszak M,Pietilä M,Koivunen P,Hakkola J,Poulton J,Morten KJ,Uusimaa J

    更新日期:2015-05-04 00:00:00

  • Synthesis and utilization of neurotransmitters: actions of subconvulsant doses of hexachlorocyclohexane isomers on brain monoamines.

    abstract::We have developed a model for the treatment of data of concentration of brain neurotransmitters (particularly serotonin and the catecholamines), in which the changes induced by any given treatment on the neurotransmitter (NT) and its main metabolite (ME) are converted into 2 new parameters named S and U, that are rela...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/0300-483x(88)90173-4

    authors: Artigas F,Martínez E,Camón L,Rodríguez Farré E

    更新日期:1988-04-01 00:00:00

  • Central/peripheral nervous system and immune responses.

    abstract::Maintenance of health is dependent on numerous regulatory interactions between organ systems. This review discusses interorgan communication between the nervous, endocrine, and immune systems and environmental and genetic influences on this neuroendocrine immune circuitry. Stresses of multiple types, including psychol...

    journal_title:Toxicology

    pub_type: 杂志文章,评审

    doi:10.1016/s0300-483x(99)00144-4

    authors: Lawrence DA,Kim D

    更新日期:2000-01-17 00:00:00

  • Effects of 20 months of ozone exposure on lung collagen in Fischer 344 rats.

    abstract::Fischer 344 rats were exposed to filtered air (controls) or to 0.12, 0.5, or 1.0 ppm of ozone for 6 h/day, 5 days/week, for 20 months. We examined lung collagen deposition and metabolism in tissue from these animals to determine whether chronic exposure of rats to ozone causes pulmonary fibrosis. We observed excess st...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/0300-483x(93)90110-e

    authors: Last JA,Gelzleichter T,Harkema J,Parks WC,Mellick P

    更新日期:1993-11-12 00:00:00

  • Development of antidotes: problems and strategies.

    abstract::Antidotes against chemical warfare agents are "orphan drugs" given that these poisonings are rare. Therefore, they are of limited interest to the pharmaceutical industry. For this reason, and recognizing the increasing threat of terrorist or asymmetrical use of chemical warfare agents, the responsibility for research ...

    journal_title:Toxicology

    pub_type: 杂志文章,评审

    doi:10.1016/j.tox.2006.07.008

    authors: Szinicz L,Worek F,Thiermann H,Kehe K,Eckert S,Eyer P

    更新日期:2007-04-20 00:00:00

  • A model system for measuring comparative toxicities of cardiotoxic drugs with cultured rat heart myocytes, endothelial cells and fibroblasts. I. Emetine, chloroquine and metronidazole.

    abstract::Neonatal rat hearts were separated into separate cultures of beating myocytes (M cells), endothelial cells (E cells) and fibroblasts (F cells). Their susceptibilities to the toxic effects of emetine, chloroquine and metronidazole were then compared using a quantitative metabolic inhibition test (QMIT) and morphologic ...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/0300-483x(84)90066-0

    authors: Wenzel DG,Cosma GN

    更新日期:1984-11-01 00:00:00

  • Cytotoxic effects of S-(dimethylarsino)-glutathione: a putative intermediate metabolite of inorganic arsenicals.

    abstract::Glutathione (GSH) plays an important role in the metabolism of arsenite and arsenate by generating arsenic-glutathione complexes. Although dimethylarsinic acid (DMA(V)) is the major metabolite of inorganic arsenicals (iAs) in urine, it is not clear how DMA(V) is produced from iAs. In the present study we report that S...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/j.tox.2006.07.009

    authors: Hirano S,Kobayashi Y

    更新日期:2006-10-03 00:00:00

  • Restoration of soman-blocked neuromuscular transmission in human and rat muscle by the bispyridinium non-oxime MB327 in vitro.

    abstract::The standard treatment of poisoning by organophosphorus (OP) nerve agents with atropine and oximes is not sufficiently effective against all types of nerve agents. Alternative therapeutic strategies are required and bispyridinium non-oximes, acting as nicotinic antagonists, were identified as promising compounds. A pr...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/j.tox.2012.02.002

    authors: Seeger T,Eichhorn M,Lindner M,Niessen KV,Tattersall JE,Timperley CM,Bird M,Green AC,Thiermann H,Worek F

    更新日期:2012-04-11 00:00:00

  • Buthionine sulfoximine (BSO) and N-(3,5-dichlorophenyl)succinimide nephrotoxicity: temporal aspects of BSO administration and BSO effects on renal transport systems.

    abstract::The agricultural fungicide, N-(3,5-dichlorophenyl)succinimide (NDPS) induces acute polyuric renal failure which is attenuated by pretreatment with the glutathione depletors, diethyl maleate or buthionine sulfoximine (BSO). In the present study, the temporal aspects of BSO attenuation of NDPS nephrotoxicity were invest...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/s0300-483x(96)03581-0

    authors: Rankin GO,Beers KW,Teets VJ,Nicoll DW,Anestis DK

    更新日期:1997-02-28 00:00:00

  • Explanation of non-additive effects in mixtures of similar mode of action chemicals.

    abstract::Many models have been developed to predict the combined effect of drugs and chemicals. Most models are classified into two additive models: independent action (IA) and concentration addition (CA). It is generally considered if the modes of action of chemicals are similar then the combined effect obeys CA; however, man...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/j.tox.2015.06.008

    authors: Kamo M,Yokomizo H

    更新日期:2015-09-01 00:00:00

  • Effects of calcium and magnesium acetates on tissue distribution of carcinogenic doses of cadmium chloride in Wistar rats.

    abstract::Previous studies have shown that magnesium, unlike calcium, prevents cadmium carcinogenesis at the subcutaneous injection site, and that neither magnesium nor calcium has any significant influence on the production of testicular tumors by cadmium in rats. The present investigation attempts to disclose the nature of th...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/0300-483x(85)90173-8

    authors: Kasprzak KS,Poirier LA

    更新日期:1985-03-15 00:00:00

  • The mouse lymphoma thymidine kinase assay for the assessment and comparison of the mutagenic activity of cigarette mainstream smoke particulate phase.

    abstract::The mouse lymphoma thymidine kinase assay (MLA) has been optimized to quantitatively determine the in vitro mutagenicity of cigarette mainstream smoke particulate phase. To test whether the MLA is able to discriminate between different cigarette types, specially constructed cigarettes each containing a single tobacco ...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/j.tox.2006.07.019

    authors: Schramke H,Meisgen TJ,Tewes FJ,Gomm W,Roemer E

    更新日期:2006-10-29 00:00:00

  • Evidence of reproductive disruption associated with neuroendocrine changes induced by UV-B filters, phthalates and nonylphenol during sexual maturation in rats of both gender.

    abstract::Endocrine disruptors (EDs) are exogenous substances or xenoestrogens natural or synthetic, capable of interacting with different systems and altering their normal hormonal regulation, being the reproductive system one of the most affected. EDs produce their effects not only by acting on nuclear steroid receptors, but ...

    journal_title:Toxicology

    pub_type: 杂志文章,评审

    doi:10.1016/j.tox.2013.05.014

    authors: Ponzo OJ,Silvia C

    更新日期:2013-09-06 00:00:00

  • Effects of exposure to BDE-99 on oxidative status of liver and kidney in adult rats.

    abstract::Little is known about the potential toxicity of polybrominated diphenyl ethers (PBDEs) on hepatic and renal tissues. In this study, we investigated the modifications in endogenous antioxidant capacity and oxidative damage in liver and kidney of rats by exposure to one of the most persistent PBDE congeners, the 2,2',4,...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/j.tox.2010.03.006

    authors: Albina ML,Alonso V,Linares V,Bellés M,Sirvent JJ,Domingo JL,Sánchez DJ

    更新日期:2010-04-30 00:00:00

  • The influence of infusion rate on the acute intravenous toxicity of phytic acid, a calcium-binding agent.

    abstract::The intravenous toxicity of phytic acid (inositol hexakisphosphate, IHP) has recently become of interest because of the potential for IHP incorporation into red blood cells to achieve a therapeutically useful shift in the hemoglobin-oxygen dissociation curve (Gersonde, K. and Nicolau, C., Blut, 39 (1979) 1). The obser...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/0300-483x(81)90022-6

    authors: Gersonde K,Weiner M

    更新日期:1981-01-01 00:00:00

  • Combined D-penicillamine and prussian blue as antidotal treatment against thallotoxicosis in rats: evaluation of cerebellar lesions.

    abstract::Rats were treated with a single dose of thallium acetate (32 mg/kg i.p.) and the antidotal effect of D-penicillamine and prussian blue given alone or in combination was assessed by means of evaluation of the thallium-induced cerebellar histological lesions. After thallium poisoning (24 h), antidotes were administered ...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/0300-483x(94)90129-5

    authors: Barroso-Moguel R,Villeda-Hernández J,Méndez-Armenta M,Ríos C,Monroy-Noyola A

    更新日期:1994-03-25 00:00:00

  • Investigations into the potential neurotoxicity induced by diselenides in mice and rats.

    abstract::It is well known that selenium is highly toxic to several species of mammals. Here we report the potential neurotoxicity of diselenides, as measured by the manifestation of seizures. The modulation of various neurotransmitter systems potentially involved in seizure episodes and death was also evaluated. The results of...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/s0300-483x(02)00423-7

    authors: Nogueira CW,Meotti FC,Curte E,Pilissão C,Zeni G,Rocha JB

    更新日期:2003-02-01 00:00:00

  • Flavonoid-induced alterations in cytochrome P450-dependent biotransformation of the organophosphorus insecticide parathion in the mouse.

    abstract::The majority of insecticides currently in use throughout the world belong to the class of the organophosphorus insecticides. Many of these compounds, such as the phosphorothioate insecticides, exert their mammalian toxicity only after undergoing metabolic activation by a variety of cytochrome P450 isoforms to produce ...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/s0300-483x(98)00125-5

    authors: Ramos S,Sultatos L

    更新日期:1998-11-16 00:00:00