Abstract:
:The U.S. EPA first signalled its intention to use benchmark dose risk techniques in 1991. Subsequently, publication of draft Guidelines for the Risk Assessment of Reproductive Toxicity data indicated the Agency's intention for wide use of the technique. In developmental toxicity experiments, a number of factors need to be considered before attempting benchmark dose calculations, as compared to the conventional NOAEL approach. For example, care in the assessment of potential litter effects (the litter is the unit of such a study) on the data and whether the data are continuous (e.g. foetal body weight) or discontinuous (e.g. specific or grouped developmental defects where the abnormality is present or absent). Two examples of the use of the benchmark dose approach will be made. First, in the analysis of foetal body weight, where a benchmark dose estimate for an agent producing a 5% decrease in mean foetal weight may be calculated from a shift in the distribution of foetal weights between groups, or by conversion of data to reflect changes in the incidence of 'small' pups (i.e. those towards the extreme of the normal range). The second example involves studies conducted on the developmental toxicity of a triazole antifungal. In the first study, the agent was clearly teratogenic, but a NOAEL was not established and thus necessitated a second study. Analysis of benchmark does estimates (e.g. for % foetuses malformed) from the first study indicated that these were not significantly changed when the data from the second study were combined (i.e. the second study did not aid the risk assessment). The benchmark dose approach has significant scientific and practical advantages over the conventional NOAEL methodology in risk assessments derived from developmental toxicity studies.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Foster PM,Auton TRdoi
10.1016/0378-4274(95)03584-2subject
Has Abstractpub_date
1995-12-01 00:00:00pages
555-9eissn
0378-4274issn
1879-3169pii
0378-4274(95)03584-2journal_volume
82-83pub_type
杂志文章abstract::The distribution of mercury to the brain following an injection of methylmercury (MeHg) or ethylmercury (EtHg) was examined in immature mice. Postnatal day (PND) 16 CD1 mice received MeHg chloride either by IM injection or by gavage. At 24 h and 7 days post-injection, total mercury concentrations were determined in bl...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2004.07.014
更新日期:2004-12-30 00:00:00
abstract::Effects of sublethal concentration (0.8 of LC50 96 h) of nickel sulphate (NiSO4 X 7H2O) on muscle glycogen and blood lactic acid levels of a freshwater teleost, Colisa fasciatus, at time intervals from 3-96 h have been recorded. Muscle glycogen levels showed a general decrease at all time intervals compared with contr...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(84)90193-0
更新日期:1984-01-01 00:00:00
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
更新日期:2006-04-10 00:00:00
abstract::The effect of endotoxin pretreatment (1 mg/kg body weight, i.p., once daily for 2 days) on the gastric mucosal damage induced by aspirin, phenylbutazone and reserpine has been studied in albino rats. When given alone, endotoxin did not produce any visibly discernible gastric lesions. It produced a significant augmenta...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(87)90168-8
更新日期:1987-06-01 00:00:00
abstract::To test the hypothesis that 3-7 ring polycyclic aromatic hydrocarbons (PAHs) are responsible for the prenatal developmental toxicity (PDT) as observed with some petroleum substances (PS), the present study evaluates the PDT potency of DMSO-extracts of 7 heavy fuel oils (HFO), varying in their PAH content, and 1 highly...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2019.08.001
更新日期:2019-10-15 00:00:00
abstract::Nitropyrene (1-NP) is classified as Group 2B carcinogen and is one of the main components of diesel exhaust particles (DEP), which are generated from incomplete combustion of automobile engines to cause human cancer or inflammatory diseases. Although many reports on the mutagenesis or carcinogenesis of 1-NP have been ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2008.10.028
更新日期:2009-01-30 00:00:00
abstract::Aluminum phosphide (AlP), a widely used fumigant and rodenticide leads to high mortality if ingested. Its toxicity is due to phosphine liberated when it comes in contact with moisture. The exact mechanism of action of phosphine is not known. In this study male Wistar rats were used. The animals received a single dose ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2012.09.020
更新日期:2012-11-23 00:00:00
abstract::Checkpoint kinase 1 (Chk1) is required for both intra-S phase and G2/M checkpoints in cell cycle, and plays critical roles in maintaining genomic stability and transducing DNA damage response. Chk1 deficiency has been shown to inhibit T-cell differentiation and resulted in severe anemia in a Chk1 heterozygous mouse mo...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2011.04.025
更新日期:2011-07-28 00:00:00
abstract::Grain should be harvested at lowest possible humidity, or immediately dried to safe storage humidity to prevent the growth of fungi. Critical steps of grain harvest like conditions of used combine harvester, temperatures and aeration are discussed on their impact on mycotoxin formation. ...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/j.toxlet.2004.04.043
更新日期:2004-10-10 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::Conversion of hepatic stellate cells (HSCs) into hepatic myofibroblasts is a necessary event during the development of liver fibrosis. DNA methyltransferase 1 (DNMT1), which catalyzes DNA methylation and subsequently leads to the transcriptional repression of profibrotic genes, is selectively induced in myofibroblasts...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2013.10.038
更新日期:2014-01-13 00:00:00
abstract::Single doses of primaquine did not produce methemoglobinemia in beagle bitches. Repeated daily administration for 12 days produced a gradually rising level of methemoglobin over that time period, unaccompanied by depletion of erythrocytic reduced glutathione. Primaquine was mutagenic in the Ames test in Salmonella typ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(87)90197-4
更新日期:1987-05-01 00:00:00
abstract::Neurological complications as well as movement disorders are relevant symptoms in animals and humans chronically exposed to dithiocarbamates. Using rat pheochromocytoma cells differentiated by NGF (PC12), we investigated whether propineb affects acetylcholine (Ach) release and the molecular mechanisms involved. Propin...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2008.08.016
更新日期:2008-11-10 00:00:00
abstract::Toxic industrial chemicals are used throughout the world to produce everyday products such as household and commercial cleaners, disinfectants, pesticides, pharmaceuticals, plastics, paper, and fertilizers. These chemicals are produced, stored, and transported in large quantities, which poses a threat to the local civ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2015.10.010
更新日期:2016-02-26 00:00:00
abstract::Dioxins are persistent environmental contaminants that cause multiple disorders in laboratory animals, including teratogenesis. In mice, the most important teratogenic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are hydronephrosis and cleft palate. Aryl hydrocarbon receptor (AHR) mediates most of the TCDD-in...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2004.02.009
更新日期:2004-05-02 00:00:00
abstract::Cocaine remains a widely abused substance. While most addicts take cocaine intranasally, a considerable number abuse cocaine by mouth. It has been assumed that after oral exposure cocaine is hydrolyzed in the stomach rendering it ineffective. This study investigated the effect of orally administered cocaine on liver f...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(01)00412-x
更新日期:2001-12-15 00:00:00
abstract::High mobility group box 1 (HMGB1) is a DNA-binding protein that is abundantly expressed in most tissues. Recently, HMGB1 has gained much attention for its regulation of immunity and inflammation. Yet its role in toluene diisocyanate (TDI)-induced asthma still remains poorly characterized. In this study, mice were sens...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2015.08.1108
更新日期:2015-11-19 00:00:00
abstract::Chromium (Cr) is widely used in industry, making its toxicity a matter of concern. Although hexavalent Cr [Cr(VI)] can promote cancer cell proliferation in several cancers, there is little evidence implicating Cr(VI) in cancer cell migration, especially in prostate cancer. We show that the Cr concentration is higher i...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2018.10.012
更新日期:2019-01-01 00:00:00
abstract::Acrylonitrile (ACN) is a widely used intermediate in the manufacture of plastics, acrylic fibers, synthetic rubbers and resins that are used in a variety of products including food containers and medical devices. ACN is a possible human carcinogen and a documented animal carcinogen, with the stomach being an important ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2011.10.018
更新日期:2012-01-25 00:00:00
abstract::In this study, we aimed to evaluate the genotoxic effects of fungicides fenarimol and propamocarb which are used to protect crops from fungi. For this reason, bone-marrow micronucleus and chromosome aberration tests were carried out in Swiss albino mice. Mice were injected with four different doses of fenarimol and pr...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2003.10.015
更新日期:2004-02-28 00:00:00
abstract::The genotoxicity of polycyclic aromatic hydrocarbons (PAHs) and nitrated PAHs may be influenced by the interaction of the compounds. In this study, our data showed that benzo[a]pyrene (BaP)-DNA adduct levels were decreased in a dose-dependent manner when the human hepatoma cell line HepG2 simultaneously treated with B...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2005.10.002
更新日期:2006-03-01 00:00:00
abstract::Mercury is the major component of dental amalgam restorative material, which typically has 50% pure elemental mercury. It is also used in some skin creams, and in the manufacturing of plastic, drugs and fungicides. The present study was designed to investigate the toxicity of methyl mercury (MeHg+) on isolated rat hep...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(93)90149-r
更新日期:1993-07-01 00:00:00
abstract::The binding of bisphenol A (BPA) and its halogenated derivatives (halogenated BPAs) to mouse peroxisome proliferator-activated receptor α ligand binding domain (mPPARα-LBD) was examined by a combination of in vitro investigation and in silico simulation. Fluorescence polarization (FP) assay showed that halogenated BPA...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2017.11.004
更新日期:2018-02-01 00:00:00
abstract::Chronic exposure to arsenic increases the risk of developing a variety of human cancers including lung carcinomas. However, the exact molecular mechanism underlying arsenic carcinogenicity remains largely unknown. Autophagy is a conserved catabolic process for maintaining cellular protein homeostasis whose defects mig...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2020.06.006
更新日期:2020-10-10 00:00:00
abstract::Methylglyoxal (MG) is a metabolite of glucose. The serum MG level is increased in diabetic patients, and MG is implicated in diabetic complications related to embryonic development injury. We previously reported cytotoxic effects of MG on mouse embryonic stem cells and blastocysts, and a further association with defec...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2010.01.007
更新日期:2010-04-01 00:00:00
abstract::The effect of dichlorophenoxyacetic acid on the transport of two non-metabolizable amino acids, 2-aminoisobutyric acid (AIB) and cycloleucine (CL) was studied in chinese hamster ovary (CHO) cells. The herbicide did not exert any direct effect on the AIB transport. However, when the pesticide was in contact with the ce...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(87)90184-6
更新日期:1987-04-01 00:00:00
abstract::Allyl alcohol-induced LDH leakage from isolated rat hepatocytes was preceded by a decrease in rhodmine 123 retention, signifying a loss of mitochondrial membrane potential. Addition of dithiothreitol (DTT) prevented the drop in membrane potential and completely prevented cell killing by allyl alcohol. In contrast, cyc...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(95)03426-9
更新日期:1995-11-15 00:00:00
abstract::General anaesthesia is an important measure in the treatment of patients suffering from organophosphorus intoxication. The intravenous anaesthetic etomidate seems to be well suited for this purpose because of its stable haemodynamics. Here we raise the question whether the anaesthetic properties of etomidate are alter...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2010.07.016
更新日期:2010-10-20 00:00:00
abstract::The aim of this study was to investigate the oxidative effects of Fe(2)O(3), benzo(a)pyrene (B(a)P) and pyrene, alone or in association (B(a)P or pyrene coated onto Fe(2)O(3) particles), in normal human embryonic lung epithelial cells (L132) in culture. We evaluated: (i) membrane integrity, through fatty acid release ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(00)00231-9
更新日期:2000-09-30 00:00:00
abstract::Excess alcohol consumption during pregnancy could lead to fetal alcohol syndrome (FAS). However, the molecular mechanism leading to craniofacial abnormality, a feature of FAS, is still poorly understood. The cranial neural crest cells (NCCs) contribute to the formation of the craniofacial bones. Therefore, NCCs expose...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2017.09.010
更新日期:2017-11-05 00:00:00