An evaluation of concentrations of styrene-7,8-oxide in rats and humans resulting from exposure to styrene or styrene-7,8-oxide and potential genotoxicity.

Abstract:

:There is potential for oral exposure of humans to styrene (ST) such as from migration of residual levels in polystyrene food containers. After absorption, ST is metabolised to styrene-7,8-oxide (SO), an alkylating epoxide. Hence, a comparison of blood burdens of SO resulting from oral exposures to ST was made with SO burdens possibly warranting genotoxic concern. A validated physiological toxicokinetic model was used for the assessment. Model calculations predicted for exposures to ST that maximum concentrations of SO in venous blood of rats and humans should not exceed 0.33 μg/ml and 0.036 μg/ml, respectively, because of saturation of the SO formation from ST. The daily area under the concentration-time curve of SO in venous blood (AUCSO) was directly proportional to the dose of ST (mg/kg body weight; BW), independent of the exposure route (inhalation or oral exposure). In resting humans, the daily AUCSO was about half that in rats at the same amount of ST/kg BW (calculated up to 100mg ST/kg BW in humans). Taking into account the results of cytogenetic studies in ST-exposed rats, it was deduced that no genotoxic effects of SO are to be expected in ST-exposed humans, at least up to a daily amount of 100mg ST/kg BW, which is equivalent to 100 times the amount originating from the Overall Migration Limit in the EU for ST migrating from food contact plastics. Therefore, no potential genotoxic concern is predicted for ST uptake from food packaging, based on the reported combined measured and modelled data.

journal_name

Toxicol Lett

journal_title

Toxicology letters

authors

Filser JG,Gelbke HP

doi

10.1016/j.toxlet.2016.02.001

subject

Has Abstract

pub_date

2016-04-15 00:00:00

pages

11-28

eissn

0378-4274

issn

1879-3169

pii

S0378-4274(16)30023-6

journal_volume

247

pub_type

杂志文章
  • Skin absorption of aniline from aqueous solutions in man.

    abstract::The skin absorption of aniline, aniline with 3% water content, and 1 and 2% aqueous aniline solutions was investigated in man. The time of exposure was 30 or 60 min. The absorbed amount of aniline was calculated on the basis of rho-aminophenol excretion in 24-h urine. The rate of aniline absorption from aqueous soluti...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/0378-4274(82)90231-4

    authors: Baranowska-Dutkeiwicz B

    更新日期:1982-03-01 00:00:00

  • Influence of maternal restraint stress on the long-lasting effects induced by prenatal exposure to perfluorooctane sulfonate (PFOS) in mice.

    abstract::The behavioral effects of concurrent maternal exposure to restraint stress and perfluorooctane sulfonate (PFOS) were assessed in the offspring of mice at 3 months of age. Plug positive females were divided into two groups. Animals were given by gavage 0 and 6mg PFOS/kg/day on gestation days 12-18. One-half of the anim...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2007.05.006

    authors: Fuentes S,Colomina MT,Vicens P,Domingo JL

    更新日期:2007-07-10 00:00:00

  • Lipoxygenase-mediated biotransformation of p-aminophenol in the presence of glutathione: possible conjugate formation.

    abstract::This study tested a hypothesis that soybean lipoxygenase (SLO), a model enzyme, may be capable of generating a glutathione (GSH) conjugate(s) from p-aminophenol (PAP). Horseradish peroxidase was employed as a positive control. GSH depletion or an increase in the absorption at 327 nm with time due to GS-PAP formation w...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/s0378-4274(99)00188-5

    authors: Yang X,Kulkarni AP

    更新日期:2000-01-05 00:00:00

  • ROS generation and MAPKs activation contribute to the Ni-induced testosterone synthesis disturbance in rat Leydig cells.

    abstract::Nickel (Ni) can disorder testosterone synthesis in rat Leydig cells, whereas the mechanisms remain unclear. The aim of this study was to investigate the role of reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPKs) in Ni-induced disturbance of testosterone synthesis in rat Leydig cells. The testo...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2018.03.016

    authors: Han A,Zou L,Gan X,Li Y,Liu F,Chang X,Zhang X,Tian M,Li S,Su L,Sun Y

    更新日期:2018-06-15 00:00:00

  • Subchronic administration of sublethal doses of thallium to rats: effects on distribution and lipid peroxidation in brain regions.

    abstract::Occupational exposure to thallium (Tl+) is known to be responsible for severe neurological manifestations in humans, including ataxia and paralysis; however, little is known yet about the precise mechanism of toxicity elicited by this heavy metal at sublethal doses and its brain distribution after chronic or subchroni...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/s0378-4274(00)00200-9

    authors: Galván-Arzate S,Martínez A,Medina E,Santamaría A,Ríos C

    更新日期:2000-07-27 00:00:00

  • PM2.5 exposure and cold stress exacerbates asthma in mice by increasing histone acetylation in IL-4 gene promoter in CD4+ T cells.

    abstract::Asthma is a common chronic inflammatory disease which severely reduces the quality of life in patients. Studies have demonstrated that both PM2.5 and cold stress contribute to the development of asthma. However, the combined effects of these two risking factors are unknown. In this study, we investigated the combined ...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2019.09.011

    authors: Zhou J,Geng F,Xu J,Peng L,Ye X,Yang D,Zhao J,Sun Q

    更新日期:2019-11-01 00:00:00

  • 3-Hydroxybenzo[a]pyrene in the urine of smokers and non-smokers.

    abstract::The people studied were male volunteers without occupational and dietary exposure to PAH: 27 smokers (10 cigarettes or more) and 27 non-smokers matched for age and socio-professional category. For each person, all the 24h voided urine samples were reassembled in a single sample. 1-Hydroxypyrene (1-OHPy) and 3-hydroxyb...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2005.09.019

    authors: Lafontaine M,Champmartin C,Simon P,Delsaut P,Funck-Brentano C

    更新日期:2006-04-10 00:00:00

  • Anti-apoptotic effect of hepatocyte growth factor from actinomycin D in hepatocyte-derived HL7702 cells is associated with activation of PI3K/Akt signaling.

    abstract::Actinomycin D (ActD) is a well-known cytotoxic chemotherapeutic reagent and the prevention of ActD-induced apoptotic cell death has been an attractive issue for biomedical investigators. Since phosphatidylinositol-3 kinase (PI3K)/Akt pathway is essential for cell survival, the present study has examined whether the pr...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2006.02.006

    authors: Li W,Cai S,Cai L,Li X

    更新日期:2006-08-20 00:00:00

  • Glutathione S-transferase cytosolic isoforms as biomarkers of polychlorinated biphenyl (Arochlor-1254) experimental contamination in rainbow trout.

    abstract::At the present work, different groups of rainbow trouts have been intraperitoneally treated with a polychlorinated biphenyls commercial mixture (Arochlor-1254) at three doses (5, 20 and 70 mg PCBs/ kg body weight) and they have been sampled at 0 (injection moment), 3, 6 and 9 weeks after xenobiotic exposure. Purificat...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/s0378-4274(02)00284-9

    authors: Pérez-López M,Nóvoa-Valiñas MC,Melgar-Riol MJ

    更新日期:2002-12-15 00:00:00

  • In vitro effect of aflatoxin B1 on rat liver macrophages (Kuffer cells).

    abstract::The effect of aflatoxin B1 on the uptake and incorporation of [3H]leucine and [3H]uridine and on phagocytosis of latex particles was studied using cultures of rat liver macrophages (Kuffer cells). Aflatoxin B1 inhibited the incorporation of both isotopes, but inhibition of uridine incorporation was greater than that o...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/0378-4274(85)90039-6

    authors: Mohapatra NK,Roberts JF

    更新日期:1985-12-01 00:00:00

  • Differential neurotoxic effects of methylmercury and mercuric sulfide in rats.

    abstract::Methylmercury (MeHg) is an environmental toxicant, while mercuric sulfide (HgS) is a main active component of cinnabar, a Chinese mineral medicine used as a sedative. Because the neurotoxicological effects of HgS were not clearly understood, in this study, we attempted to compare HgS with MeHg in various physiological...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2006.12.006

    authors: Chuu JJ,Liu SH,Lin-Shiau SY

    更新日期:2007-03-08 00:00:00

  • Cytochrome P450 isozymes involved in the metabolism of phenol, a benzene metabolite.

    abstract::Benzene is an occupational and environmental toxicant. The major health concern for humans is acute myelogenous leukemia. To exert its toxic effects, benzene must be metabolized by cytochrome P450 to phenol and subsequently to catechol and hydroquinone. Previous research has implicated CYP2E1 in the metabolism of phen...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/s0378-4274(01)00441-6

    authors: Powley MW,Carlson GP

    更新日期:2001-12-15 00:00:00

  • Morphological and transcriptomic effects of endocrine modulators on the gonadal differentiation of chicken embryos: The case of tributyltin (TBT).

    abstract::Morphological malformations induced by tributyltin (TBT) exposure during embryonic development have already been characterized in various taxonomic groups, but, nonetheless, the molecular processes underlying these changes remain obscure. The present study provides the first genome-wide screening for differentially ex...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2017.11.019

    authors: Scheider J,Afonso-Grunz F,Jessl L,Hoffmeier K,Winter P,Oehlmann J

    更新日期:2018-03-01 00:00:00

  • Antigenotoxic effects of cimetidine against benzene induced micronuclei in mouse bone marrow erythrocytes.

    abstract::An in vivo micronucleus assay using Balb/C male mice was used to examine antigenotoxic effects of cimetidine (CM) on benzene (BZN) induced genotoxic effects. CM not only has therapeutic and immunomudolatory role, but it has also been shown to protect bone marrow stem cells from radiation induced clastogenic effects. T...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/s0378-4274(98)00138-6

    authors: Mozdarani H,Kamali S

    更新日期:1998-09-30 00:00:00

  • TLR4 is a target of environmentally relevant concentration of lead.

    abstract::Lead (Pb) alters the susceptibility to different pathogens suggesting that macrophage-mediated defense mechanisms, through activation of toll-like receptors (TLRs), may be affected by Pb. The aim of this study was to test whether activation of TLR4 is a targeted molecule to the effect of environmentally relevant Pb co...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2012.09.009

    authors: Luna AL,Acosta-Saavedra LC,Martínez M,Torres-Avilés N,Gómez R,Calderón-Aranda ES

    更新日期:2012-11-15 00:00:00

  • Effects of inhalational anesthetics on alpha2-adrenergic signaling in isolated platelets.

    abstract::(1) The hypothesis that inhalational anesthetics affect G-protein linked alpha2 adrenergic signaling pathway was investigated using human platelets as a model system. (2) Alpha2 receptor stimulation by UK-14304, a potent and selective agonist, inhibits cAMP production induced by prostaglandin I2 (PGI2). (3) Brief stim...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/s0378-4274(98)00174-x

    authors: Pentyala S,Moller D,Chowdhury A,Sung KY,Rebecchi M

    更新日期:1998-11-23 00:00:00

  • N-nitrososdimethylamine is activated in microsomes from hepatocytes to reactive metabolites which damage DNA of non-parenchymal cells in rat liver.

    abstract::The liver carcinogen N-nitrosodimethylamine (NDMA) has to be metabolically activated by specific cytochromes before it can react with cellular macromolecules (e.g. proteins or DNA). Although hepatocytes are believed to be responsible for this activation, the liver tumours originate mainly from non-parenchymal cells (N...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/s0378-4274(01)00400-3

    authors: Frei E,Kuchenmeister F,Gliniorz R,Breuer A,Schmezer P

    更新日期:2001-09-15 00:00:00

  • Elevation of metallothionein level in preneoplastic lesions during chemical hepatocarcinogenesis of the Fischer 344 rat.

    abstract::Metallothionein (MT) is inducible by various stimuli such as metals and physiological stress. Although elevated MT expression in certain type of tumors has been reported, there are few data available on the roles of MT in tumor formation. In this study, we immunohistochemically examined MT expression in gluthathione S...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/s0378-4274(99)00127-7

    authors: Sawaki M,Enomoto K,Hattori A,Tsuzuki N,Sawada N,Mori M

    更新日期:1999-07-30 00:00:00

  • In vitro hydrolysis of methyl acetate, a limitation in application of head-space gas-chromatography in biological monitoring of exposure.

    abstract::Stoichiometric conversion of methyl acetate to methanol in vitro was detected when methyl acetate was incubated with blood for 2 to 8 h. The velocity of the reaction was so fast that almost all of methyl acetate disappeared in 8 h. The methanol formation was further confirmed by means of gas-chromatography-mass spectr...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/0378-4274(92)90028-i

    authors: Mizunuma K,Kawai T,Yasugi T,Horiguchi S,Iwami O,Ikeda M

    更新日期:1992-09-01 00:00:00

  • Indirect human exposure to pharmaceuticals via drinking water.

    abstract::There are numerous observations of pharmaceuticals (or their metabolites) as contaminants in wastewater, surface water and groundwater. This implies a potential for indirect human exposure to pharmaceuticals via drinking water supplies. Various effect benchmarks may be employed in an evaluation of the significance of ...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/s0378-4274(03)00071-7

    authors: Webb S,Ternes T,Gibert M,Olejniczak K

    更新日期:2003-05-15 00:00:00

  • Environmental contaminants and human health in the Arctic.

    abstract::Monitoring of human exposure to persistent organic pollutants POPs and heavy metals have taken place since 1994 in a circumpolar study conducted under the Arctic monitoring and assessment programme (AMAP). The study has confirmed that Arctic populations relying on marine food (Inuit) have an exposure level of POPs and...

    journal_title:Toxicology letters

    pub_type: 杂志文章,评审

    doi:10.1016/s0378-4274(99)00203-9

    authors: Hansen JC

    更新日期:2000-03-15 00:00:00

  • Sister-chromatid exchanges in the lymphocytes of people exposed to environmental cadmium.

    abstract::Sister-chromatid exchanges (SCEs) were analyzed from peripheral lymphocyte cultures of 8 men and 16 women who had been exposed to environmental cadmium (Cd), and 6 controls. Average Cd concentrations in blood of the Cd-polluted group were 8.9 micrograms/l for men and 10.0 micrograms/l for women. These were no signific...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/0378-4274(86)90120-7

    authors: Nogawa K,Tsuritani I,Yamada Y,Kido T,Honda R,Ishizaki M,Kurihara T

    更新日期:1986-09-01 00:00:00

  • Effect of ketamine pretreatment on cocaine-mediated hepatotoxicity in rats.

    abstract::Cocaine (COC) produces hepatotoxicity by a mechanism, which remains undefined, but has been linked to its oxidative metabolism. Ketamine (KET) is also a potentially hepatotoxic agent. The abuse of KET with COC is currently popular among young abusers therefore; this study was conducted to investigate the possible pote...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2004.04.035

    authors: Rofael HZ

    更新日期:2004-09-25 00:00:00

  • Molecular and kinetic determinants of local anaesthetic action on sodium channels.

    abstract::(1) Local anaesthetics (LA) rely for their clinical actions on state-dependent inhibition of voltage-dependent sodium channels. (2) Single, batrachoxin-modified sodium channels in planar lipid bilayers allow direct observation of drug-channel interactions. Two modes of inhibition of single-channel current are observed...

    journal_title:Toxicology letters

    pub_type: 杂志文章,评审

    doi:10.1016/s0378-4274(98)00192-1

    authors: French RJ,Zamponi GW,Sierralta IE

    更新日期:1998-11-23 00:00:00

  • Increased o- and p-cresol/hippuric acid ratios in the urine of four strains of rat exposed to toluene at thousands-ppm levels.

    abstract::Rats (Fisher, Wistar, Donryu and Sprague-Dawley strains) were exposed to 5 approximately 3500 ppm toluene for 8 h, and urine samples were analyzed for hippuric acid and cresols. While hippuric acid increased in proportion to the exposure concentration, a sharp increase in o-cresol excretion was observed at high toluen...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/0378-4274(84)90134-6

    authors: Inoue O,Seiji K,Ishihara N,Kumai M,Ikeda M

    更新日期:1984-11-01 00:00:00

  • The effects of methylmercury on endogenous dopamine efflux from mouse striatal slices.

    abstract::The present study investigated the effects of in vitro methylmercury (MeHg) exposure on endogenous dopamine (DA) efflux from mouse striatal slices. MeHg produced a concentration-dependent increase in the spontaneous efflux of DA which was independent of the availability of Ca2+ in the superfusion medium. The Ca(2+)-de...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/s0378-4274(96)03787-3

    authors: Kalisch BE,Racz WJ

    更新日期:1996-12-01 00:00:00

  • In vitro effects of mercury-selenium compounds on enzymes.

    abstract::In vitro effects of mercury-selenium compounds, as compared with mercurials, against glucose-6-phosphate dehydrogenase (G6PD), catalase and trypsin were studied. Inhibitory potencies of two mercury-selenium (Hg-Se) compounds, bis(methylmercuric) selenide (BMS), and a reaction product of HgCl2, Na2SeO3 and glutathione ...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/0378-4274(82)90052-2

    authors: Mochizuki Y,Kobayashi T,Doi R

    更新日期:1982-12-01 00:00:00

  • Activation of styrene to styrene oxide in hepatocytes and subcellular fractions of rat liver.

    abstract::The oxidation of styrene to styrene oxide and the hydration of this metabolite to styrene glycol was investigated in hepatocytes, 9000 x g supernatant (S9) and the microsomal fraction from rat liver. Similar amounts of free styrene oxide were found in microsomes, hepatocytes and S9. However, on the basis of the format...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/0378-4274(84)90120-6

    authors: Belvedere G,Elovaara E,Vainio H

    更新日期:1984-11-01 00:00:00

  • Benzodiazepines medazepam and midazolam are activators of pregnane X receptor and weak inducers of CYP3A4: investigation in primary cultures of human hepatocytes and hepatocarcinoma cell lines.

    abstract::Benzodiazepines have wide-spread used in pharmacotherapy for their anxiolytic, myorelaxant, hypnotic, amnesic and anticonvulsive properties. Despite benzodiazepines are used in clinics over 50 years, they have not been surprisingly tested for capability to induce major drug-metabolizing cytochromes P450. In the curren...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2010.01.004

    authors: Vrzal R,Kubesova K,Pavek P,Dvorak Z

    更新日期:2010-03-15 00:00:00

  • Effects of blowing sand fine particles on plasma membrane permeability and fluidity, and intracellular calcium levels of rat alveolar macrophages.

    abstract::Ambient fine particulate matter (PM2.5, particulates with an aerodynamic diameter < or = 2.5 microm) can suppress alveolar macrophage (AM) functions, but the data concerning the effects of blowing sand PM2.5 on AMs remain limited. The aim of the present study is to investigate the influences of blowing sand PM2.5 on A...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2005.01.010

    authors: Geng H,Meng Z,Zhang Q

    更新日期:2005-06-17 00:00:00