Abstract:
:Benchmark dose (BMD) modeling is now the state of the science for determining the point of departure for risk assessment. Key advantages include the fact that the modeling takes account of all of the data for a particular effect from a particular experiment, increased consistency, and better accounting for statistical uncertainties. Despite these strong advantages, disagreements remain as to several specific aspects of the modeling, including differences in the recommendations of the US Environmental Protection Agency (US EPA) and the European Food Safety Authority (EFSA). Differences exist in the choice of the benchmark response (BMR) for continuous data, the use of unrestricted models, and the mathematical models used; these can lead to differences in the final BMDL. It is important to take confidence in the model into account in choosing the BMDL, rather than simply choosing the lowest value. The field is moving in the direction of model averaging, which will avoid many of the challenges of choosing a single best model when the underlying biology does not suggest one, but additional research would be useful into methods of incorporating biological considerations into the weights used in the averaging. Additional research is also needed regarding the interplay between the BMR and the UF to ensure appropriate use for studies supporting a lower BMR than default values, such as for epidemiology data. Addressing these issues will aid in harmonizing methods and moving the field of risk assessment forward.
journal_name
Crit Rev Toxicoljournal_title
Critical reviews in toxicologyauthors
Haber LT,Dourson ML,Allen BC,Hertzberg RC,Parker A,Vincent MJ,Maier A,Boobis ARdoi
10.1080/10408444.2018.1430121subject
Has Abstractpub_date
2018-05-01 00:00:00pages
387-415issue
5eissn
1040-8444issn
1547-6898journal_volume
48pub_type
杂志文章,评审abstract::Aniline (in the form of its hydrochloride) has been shown to induce a rather rare spectrum of tumors in the spleen of Fischer 344 rats. The dose levels necessary for this carcinogenic activity were in a range where also massive effects on the blood and non-neoplastic splenotoxicity as a consequence of methemoglobinemi...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.1080/10408440500442384
更新日期:2005-12-01 00:00:00
abstract::An earlier review of the toxicity of glyphosate and the original Roundup™-branded formulation concluded that neither glyphosate nor the formulation poses a risk for the production of heritable/somatic mutations in humans. The present review of subsequent genotoxicity publications and regulatory studies of glyphosate a...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.3109/10408444.2013.770820
更新日期:2013-04-01 00:00:00
abstract:BACKGROUND:Exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) is ubiquitous in most regions of the world. The most commonly studied PFASs are perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA). Animal studies indicate that maternal PFAS exposure is associated with reduced fetal growth. Howeve...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.3109/10408444.2014.952400
更新日期:2015-01-01 00:00:00
abstract::Hydroquinone (HQ) is a high-volume commodity chemical used as a reducing agent, antioxidant, polymerization inhibitor, and chemical intermediate. It is also used in over-the-counter (OTC) drugs as an ingredient in skin lighteners and is a natural ingredient in many plant-derived products, including vegetables, fruits,...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.1080/10408449991349221
更新日期:1999-05-01 00:00:00
abstract::The International Agency for Research on Cancer (IARC, 2004) recently reevaluated the epidemiological data on formaldehyde and concluded that there was "strong but not sufficient evidence for a causal association between leukaemia and occupational exposure to formaldehyde." This conclusion was tempered since a mechani...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.1080/10408440500533208
更新日期:2006-02-01 00:00:00
abstract::Quantitation of morphological changes in the nervous system is valuable for demonstrating different regions and cell types involved in a pathological process. Quantitative anatomical studies are numerous, whereas quantitations of pathological conditions are relatively few. This seems to be due partly to technical diff...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.3109/10408448209037456
更新日期:1982-09-01 00:00:00
abstract::Bacterial systems have long been of use in toxicology. In addition to providing general models of enzymes and paradigms for biochemistry and molecular biology, they have been adapted to practical genotoxicity assays. More recently, bacteria also have been used in the production of mammalian enzymes of relevance to tox...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.3109/10408449609037477
更新日期:1996-09-01 00:00:00
abstract::The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.3109/10408449209146312
更新日期:1992-01-01 00:00:00
abstract::As long as no effective malaria vaccine is available, chemotherapy belongs to the most important weapons fighting malaria. One of the most promising new drug developments is the sesquiterpene artemisinin (ARS) and its derivatives, e.g., artemether, arteether, and sodium artesunate. Large clinical studies and meta-anal...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.3109/10408441003610571
更新日期:2010-05-01 00:00:00
abstract::Two important challenges for inhalation toxicologists involve the elucidation of mechanisms of lung toxicity caused by inhalation of chemicals or particulate materials, as well as the extrapolation of animal data to humans. Because risk estimates of toxicity generally are dependent upon experimental data for which a v...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.3109/10408448909037474
更新日期:1989-01-01 00:00:00
abstract::Little consistency exists in the methodology for toxicological testing of aerosolized nanoparticles used in in vitro, air-interfaced culture (AIC) exposure systems for engineered nanoparticles (ENPs) risk-assessment, preventing inter-laboratory comparisons to identify dose thresholds for adverse effects. These inconsi...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章
doi:10.1080/10408444.2016.1223015
更新日期:2017-03-01 00:00:00
abstract::The application of chemical-specific toxicokinetic or toxicodynamic data to address interspecies differences and human variability in the quantification of hazard has potential to reduce uncertainty and better characterize variability compared with the use of traditional default or categorically-based uncertainty fact...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.1080/10408444.2017.1303818
更新日期:2017-10-01 00:00:00
abstract::Aerobic organisms by definition require oxygen, and the importance of iron in aerobic respiration has long been recognized, but despite their beneficial roles, these elements can pose a real threat to the organism. During oxygen reduction, reactive species such as O2-. and H2O2 are formed readily. Iron can combine wit...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.3109/10408448709089856
更新日期:1987-01-01 00:00:00
abstract::The pharmacokinetic basis for the design of toxicity tests is discussed with reference to the absorption and clearance of drugs. The absorption and clearance of a wide range of drugs by laboratory animals and man has been examined and reviewed to provide a firm basis against which new drugs can be compared. Some pitfa...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.3109/10408448409044214
更新日期:1984-01-01 00:00:00
abstract::Styrene is metabolized to styrene oxide, a direct-acting mutagen and carcinogen. Styrene oxide reacts with DNA mainly at the N-7 position in guanine, but also at other sites and with other bases. Substitution occurs at both the alpha- and beta-positions of the styrene molecule. Experiments with radiolabeled styrene an...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.3109/10408449409020139
更新日期:1994-01-01 00:00:00
abstract::A 1999 California state agency cancer potency (CP) evaluation of methyl tert-butyl ether (MTBE) assumed linear risk extrapolations from tumor data were plausible because of limited evidence that MTBE or its metabolites could damage DNA, and based such extrapolations on data from rat gavage and rat and mouse inhalation...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.3109/10408444.2015.1052367
更新日期:2015-01-01 00:00:00
abstract::Histamine poisoning can result from the ingestion of food containing unusually high levels of histamine. Fish are most commonly involved in incidents of histamine poisoning, although cheese has also been implicated on occasion. The historic involvement of tuna and mackerel in histamine poisoning led to the longtime us...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.3109/10408448609023767
更新日期:1986-01-01 00:00:00
abstract::This article explores the occurrence of U-shaped dose responses induced by neuroprotective agents in animal stroke and traumatic brain injury (TBI) screening/preclinical studies. The assessment was stimulated by suggestions that U-shaped dose responses may be common for neuroprotective agents in stroke and TBI models,...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.1080/10408440802014287
更新日期:2008-01-01 00:00:00
abstract::This article is a comprehensive assessment of the quantitative features of the dose response for neuroprotective agents and their underlying mechanistic foundations. The data were derived from published studies using numerous primary neuronal cell cultures and neuronal cell lines. These biological models assessed norm...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.1080/10408440801981973
更新日期:2008-01-01 00:00:00
abstract::Biodiesel fuels are alternatives to petrodiesel, especially in the transport sector where they have lower carbon footprint. Notwithstanding the environmental benefit, biodiesel fuels may have other toxicological properties than petrodiesel. Particulate matter (PM) from petrodiesel causes cancer in the lung as a conseq...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.1080/10408444.2020.1762541
更新日期:2020-05-01 00:00:00
abstract::The weight of the evidence from metabolic studies, short-term tests, animal bioassays, and epidemiological studies indicates that cyclamate (CHS) is not carcinogenic by itself; however, there is evidence from in vitro and in vivo studies in animals that implies it may have cancer-promoting or cocarcinogenic activity. ...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.3109/10408449209146307
更新日期:1992-01-01 00:00:00
abstract::Nephrogenic systemic fibrosis (NSF) is an iatrogenic scleroderma-like fibrosing systemic disorder occurring in patients with severe or end-stage renal disease. It was established as a new clinical entity in the year 2000. A causal role for gadolinium chelates (GC), widely used as contrast agents for magnetic resonance...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.3109/10408444.2014.955568
更新日期:2014-11-01 00:00:00
abstract::A qualitative review of the epidemiological literature on the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) and health after 2001 is presented. In order to compare the exposure of the general population, bystanders and occupational groups, their urinary levels were also reviewed. In the general population, 2,4-D ex...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.3109/10408444.2012.710576
更新日期:2012-10-01 00:00:00
abstract::Quantitative weight of evidence (QWoE) provides a framework and process for evaluating different toxicological studies based on quality and relevance of the results. This framework allows for data from these studies to be combined in separate lines of evidence to address causality, and relevance to environmental risks...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.1080/10408444.2019.1701985
更新日期:2019-09-01 00:00:00
abstract::The field of toxicology is currently undergoing a global paradigm shift to use of in vitro approaches for assessing the risks of chemicals and drugs in a more mechanistic and high throughput manner than current approaches relying primarily on in vivo testing. However, reliance on in vitro data entails a number of new ...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.3109/10408444.2012.692115
更新日期:2012-09-01 00:00:00
abstract::Globally, oral cancer is one of the ten common cancers. In some parts of the world, including the Indian subcontinent, oral cancer is a major cancer problem. Tobacco use is the most important risk factor for oral cancer. The most common form of tobacco use, cigarette smoking, demonstrates a very high relative risk--in...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.3109/10408449609017930
更新日期:1996-01-01 00:00:00
abstract::The critical review of the literature cited on pharmacology, toxicology, metabolism, and safety assessment clearly demonstrates that cocoa per se has not attracted a great deal of scientific interest because of its long-term usage with no reported adverse effects that would be injurious to man. On the other hand, a gr...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.3109/10408448209037495
更新日期:1982-01-01 00:00:00
abstract::The IPCS Human Relevance Framework was evaluated for a DNA-reactive (genotoxic) carcinogen, 4-aminobiphenyl, based on a wealth of data in animals and humans. The mode of action involves metabolic activation by N-hydroxylation, followed by N-esterification leading to the formation of a reactive electrophile, which bind...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.1080/10408440600977651
更新日期:2006-11-01 00:00:00
abstract::In 2015, the International Agency for Research on Cancer (IARC) published a monograph concluding there was strong evidence for genotoxicity of glyphosate and glyphosate formulations and moderate evidence for genotoxicity of the metabolite aminomethylphosphonic acid (AMPA). These conclusions contradicted earlier extens...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章
doi:10.1080/10408444.2016.1214680
更新日期:2016-09-01 00:00:00
abstract::Examination of the eye in experiments designed to test the toxicity of drugs or chemicals is of considerable importance and the investigator must have a clear idea of the spontaneous eye changes he can expect in the test species. We have attempted to review the literature relating to commonly used laboratory animals--...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.3109/10408448409023759
更新日期:1984-01-01 00:00:00