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：:Although formaldehyde (FA) has been classified as a human leukemogen, the mechanisms of leukemogenesis remain elusive. Previously, using colony-forming assays in semi-solid media, we showed that FA exposure in vivo and in vitro was toxic to human hematopoietic stem/progenitor cells. In the present study, we have appli...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2013.10.028
更新日期：2014-01-13 00:00:00
abstract：:Melamine is commonly used in a variety of consumer products such as furniture, dining ware, and food utensils. The chemical infamously gained worldwide attention by its illegal addition to a variety of foodstuffs in order to falsify protein content, which led to serious, sometimes fatal, health impacts in children and...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/j.toxlet.2017.07.893
更新日期：2017-10-05 00:00:00
abstract：:Triphenyltin (TPT) is an organotin compound and may be an endocrine disruptor, impairing the male reproductive system. However, the effect of short-term TPT exposure on stem Leydig cell regeneration later on remains unknown. Here, we show that TPT affects stem Leydig cell regeneration in the adult rat testis. Adult ma...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2019.02.010
更新日期：2019-05-15 00:00:00
abstract：:Dichloromethane (DCM) elimination and carboxyhemoglobin (COHb) generation were examined in adult female SD rats pretreated with a glutathione (GSH) depletor(s). Rats were treated with either buthionine sulfoximine (BSO; 2 mmol/kg, i.p.), diethylmaleate (DEM; 3 mmol/kg, i.p.), phorone (PHO; 1 mmol/kg, i.p.) or BSO plus...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(01)00523-9
更新日期：2002-03-24 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：:The possible embryotoxic effects of cyclohexylamine hydrochloride doses (expressed as free base) of 10, 30 and 100 mg/kg of body weight per day administered orally in water to mice and rats from the 6th to 15th day post-coitum were investigated. Treatment with daily doses of up to 100 mg/kg of body weight to mice and ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(83)90049-8
更新日期：1983-06-01 00:00:00
abstract：:Chloroacetonitrile (CAN) is a disinfection by-product of chlorination of drinking water. The present study was designed to investigate the potential adverse effects of maternal exposure to CAN on fetal liver in mice. Based on an initial dose-response experiment, CAN (25mg/(kgday)) was given orally to pregnant mice at ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2009.06.867
更新日期：2009-10-28 00:00:00
abstract：:Ambient and biological monitoring was undertaken among tobacco processors who are chronically exposed to tobacco particulates via nasopharyngeal and cutaneous routes. Ambient monitoring revealed that the inspirable dust concentration was 150-fold higher in the tobacco factory than in the control environment, and was a...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(99)00097-1
更新日期：1999-09-05 00:00:00
abstract：:The effect of two polyamino-polycarboxylic acids, N-(2-hydroxyethyl) ethylenediamine triacetic acid (HEDTA) and diethylenetriamine penta-acetic acid (DTPA) and two thiol-chelating agents, sodium diethyldithiocarbamate (DDC) and dimercaptosuccinic acid (DMS) on the excretion of manganese (Mn) in rabbits given Mn i.p. w...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(80)90180-0
更新日期：1980-08-01 00:00:00
abstract：:Two-week oral administration of MDL-19,660, a triazole antidepressant compound, resulted in a dose-related thrombocytopenia in rats given 40-360 mg/kg/d and dogs treated with 5-50 mg/kg/d. Consumptive loss of platelets was not apparent since splenomegaly, hemorrhage, microscopic thrombi or prolonged coagulation times ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(91)90098-q
更新日期：1991-04-01 00:00:00
abstract：:In C57BL/6 mice, aryl hydrocarbon hydroxylase (AHH) increased 1 day after treatment with 3-methylcholanthrene, and induction of UDP-glucuronyl transferases for 3-hydroxybenzo(a)pyrene, p-nitrophenol and bilirubin in the liver microsomes was observed 2 to 5 days later. In DBA/2 mice, neither AHH nor transferase activit...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(80)90146-0
更新日期：1980-01-01 00:00:00
abstract：:Chlordimeform (Cdf) is readily absorbed through the skin of pesticide applicators. It also enters the body when breathed into the lungs. Cdf can be found in the urine of workers who handle or are involved in applying pesticide products which contain the chemical, even when they are wearing special protective clothing ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(86)90069-x
更新日期：1986-10-01 00:00:00
abstract：:Protein S-glutathionation has been demonstrated to be one of the cellular responses under oxidative stress and may be involved in many cellular metabolisms. In this study, the effect of redox cycling bipyridylium compounds, paraquat and diquat, on this protein modification was investigated. Male Sprague-Dawley rats we...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(95)03621-0
更新日期：1996-02-01 00:00:00
abstract：:3-methyladenine DNA glycosylase (AlkD) belongs to a new family of DNA glycosylases; it initiates repair of cytotoxic and promutagenic alkylated bases (its main substrates being 3-methyladenine and 7-methylguanine). The modification of the comet assay (single cell gel electrophoresis) using AlkD enzyme thus allows asse...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2011.10.005
更新日期：2012-01-05 00:00:00
abstract：:The industrial solvent dioxane (1,4-diethylene dioxide) was evaluated for teratogenic potential in Sprague-Dawley rats. The compound was administered on days 6-15 of gestation by gavage (0, 0.25, 0.5 and 1.0 ml/kg/day). A slight maternal toxicity, as evidenced by reduced weight gain, was observed with 1.0 ml/kg. Anima...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(85)90189-4
更新日期：1985-07-01 00:00:00
abstract：:Letimide is a new efficient analgesic salicylate derivative. In this study we evaluated its cytogenetic and teratogenic potential. For chromosomal aberrations and sister chromatid exchange analysis we tested 250, 375, 500 and 625 micrograms/ml of letimide in human lymphocyte cultures in vitro, and for the in vivo cyto...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(91)90095-n
更新日期：1991-04-01 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：:Lanthanides, because of their diversified physical and chemical effects, have been widely used in a number of fields. As a result, more and more lanthanides are entering into the environment and eventually accumulated in human body. Recently, a new medicine, lanthanum carbonate (Fosrenol), has been used to treat chron...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2006.02.003
更新日期：2006-08-20 00:00:00
abstract：:Mechanism of PAH mixtures, using granulosa tumour cells, was investigated. Cells were exposed to a mixture of all 16 priority PAHs (M1) or a mixture of five PAHs not classified as human carcinogens (M2). The effect of siAHR, siAHRR and siNFKB2 on the expression of CYP1A1, CYP1B1, GSTM1, ERα, AR and cell proliferation ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2019.04.008
更新日期：2019-08-01 00:00:00
abstract：:Safety assessment procedures still rely heavily if not exclusively on the results of tests carried out in laboratory animals, then extrapolated to man. There are few examples of environmental compounds examined extensively enough in both man and animals to permit a critical comparison of the accuracy of such risk asse...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(92)90236-d
更新日期：1992-12-01 00:00:00
abstract：:N-acetyl-beta-D-glucosaminidase (NAG) activity in urine was measured in patients with 'itai-itai' disease, from chronically advanced cadmium poisoning. Elevation of NAG activity, however, was not so marked as that of beta 2-microglobulin (beta 2-MG) in the urine of patients and suspected patients. We conclude that the...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(83)90193-5
更新日期：1983-05-01 00:00:00
abstract：:Triptolide (TP) is the main ingredient of Chinese herb Tripterygium wilfordii Hook f. (TWHF). Despite of its multifunction in pharmaceutics, accumulating evidences showed that TP caused obvious hepatotoxicity in clinic. The current study investigated the role of Notch1 signaling in TP-induced hepatotoxicity. Our data ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2018.10.024
更新日期：2019-01-01 00:00:00
abstract：:The proceedings in this volume suggest several important future research needs. Research is needed to validate modeling in toxicology in order to support the use of the general approach of modeling, either for structure-activity relationships (SAR) or physiologically based pharmacokinetics (PBPK), by regulators. Resea...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/0378-4274(95)03382-u
更新日期：1995-09-01 00:00:00
abstract：:When pregnant mice were exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the average time to eye opening in the offspring was shortened by about a day. How acceleration of eye opening by TCDD occurs remains unknown. To reveal the underlying mechanisms of the accelerated eye opening, pregnant mice were intraperit...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2010.04.001
更新日期：2010-07-01 00:00:00
abstract：:Styrene-acrylonitrile trimer (SAN Trimer), a mixture of six isomers (four isomers of 4-cyano-1,2,3,4-tetrahydro-alpha-methyl-1-naphthaleneacetonitrile [THAN] and two isomers of 4-cyano-1,2,3,4-tetrahydro-1-naphthaleneproprionitrile [THNP]), is a by-product of a specific production process of styrene-acrylonitrile poly...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2008.01.016
更新日期：2008-04-21 00:00:00
abstract：:Considering of novel biochemical modulation by some foods and beverages, we have performed screening for green tea components that have enhancing effects on doxorubicin (DOX) induced antitumor activity. Components, such as caffeine, theanine, (-)-epigallocatechin gallate (EGCG) and flavonoids have inhibitory effects o...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(99)00290-8
更新日期：2000-04-03 00:00:00
abstract：:The E-rosetting profiles of T-cells were studied in 47 subjects with a history of poly-drug and alcohol abuse, and compared with 15 normal controls. No change was evident in numbers of total rosette-forming cells (TRFC). However, there was reduction in active and high-affinity rosette-forming cells (ARFC and HARFC). T...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(91)90208-n
更新日期：1991-08-01 00:00:00
abstract：:Exposition to cadmium (Cd) has been linked to bone metabolism alterations and occurrence of osteoporosis. Despite its known renal toxicity which indirectly disrupts bone metabolism through impairment of vitamin D synthesis, increasing evidence argues for the direct action of Cd on bone-forming osteoblasts. Indeed, acc...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2012.10.006
更新日期：2012-12-17 00:00:00
abstract：:A number of studies have demonstrated that co-exposure to low levels of melamine and cyanuric acid elicits renal toxicity due to the formation of melamine cyanurate crystals in the kidney nephrons. In this work, we investigated if co-exposure of rats to these compounds leads to alterations in the expression of the gen...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2011.07.009
更新日期：2011-10-10 00:00:00
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
更新日期：1998-11-23 00:00:00
