Abstract:
:We examine how Bayesian network (BN) learning and analysis methods can help to meet several methodological challenges that arise in interpreting significant regression coefficients in exposure-response regression modeling. As a motivating example, we consider the challenge of interpreting positive regression coefficients for blood lead level (BLL) as a predictor of mortality risk for nonsmoking men. We first note that practices such as dichotomizing or categorizing continuous confounders (e.g. income), omitting potentially important socioeconomic confounders (e.g. education), and assuming specific parametric regression model forms leave unclear to what extent a positive regression coefficient reflects these modeling choices, rather than a direct dependence of mortality risk on exposure. Therefore, significant exposure-response coefficients in parametric regression models do not necessarily reveal the extent to which reducing exposure-related variables (e.g. BLL) alone, while leaving fixed other correlates of exposure and mortality risks (e.g. education, income, etc.) would reduce adverse outcome risks (e.g. mortality risks). We then consider how BN structure-learning and inference algorithms and nonparametric estimation methods (partial dependence plots) can be used to clarify dependencies between variables, variable selection, confounding, and quantification of joint effects of multiple factors on risk, including possible high-order interactions and nonlinearities. We conclude that these details must be carefully modeled to determine whether a data set provides evidence that exposure itself directly affects risks; and that BN and nonparametric effect estimation and uncertainty quantification methods can complement regression modeling and help to improve the scientific basis for risk management decisions and policy-making by addressing these issues.
journal_name
Crit Rev Toxicoljournal_title
Critical reviews in toxicologyauthors
Cox LA Jrdoi
10.1080/10408444.2020.1787329subject
Has Abstractpub_date
2020-08-01 00:00:00pages
539-550issue
7eissn
1040-8444issn
1547-6898journal_volume
50pub_type
杂志文章,评审abstract::Rare adverse reactions to drugs that are of unknown etiology, or idiosyncratic reactions, can produce severe medical complications or even death in patients. Current hypotheses suggest that metabolic activation of a drug to a reactive intermediate is a necessary, yet insufficient, step in the generation of an idiosync...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.1080/10408440590935620
更新日期:2005-04-01 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::Neuroexcitatory symptoms of acute poisoning of vertebrates by pyrethroids are related to the ability of these insecticides to modify electrical activity in various parts of the nervous system. Repetitive nerve activity, particularly in the sensory nervous system, membrane depolarization, and enhanced neurotransmitter ...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.3109/10408449009089875
更新日期:1990-01-01 00:00:00
abstract::Although benzene is best known as a compound that causes bone marrow depression leading to aplastic anemia in animals and humans, it also induces acute myelogenous leukemia in humans. The epidemiological evidence for leukemogenesis in humans is contrasted with the results of animal bioassays. This review focuses on se...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.3109/10408449409021605
更新日期:1994-01-01 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::The incidence rates of a wide range of diseases and conditions have increased over the last decades. There is controversy over the origin of these increases, whether they are caused by exposure to compounds thought to have an effect on the endocrine system, the "endocrine disruption theory", or whether some other fact...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.1080/10408444.2018.1541073
更新日期:2018-10-01 00:00:00
abstract::A high intake of fruits and vegetables is associated with a lower risk of cancer. In this context, considerable attention is paid to Asian populations who consume high amounts of soy and soy-derived isoflavones, and have a lower risk for several cancer types such as breast and prostate cancers than populations in West...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.3109/10408444.2010.541900
更新日期:2011-07-01 00:00:00
abstract::A nomenclature for tumors of the mouse hematopoietic system is proposed. This nomenclature, which will be particularly appropriate for use in safety assessment studies, employs basic cytologic terminology, and subclassifications may take into consideration tissue sites and the presence or absence of leukemia. Analysis...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.3109/10408448409034080
更新日期:1984-01-01 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::In recent years, many spatial epidemiological studies that use proximity of subjects to putative sources as a surrogate for exposure have been published and are increasingly cited as evidence of environmental problems requiring public health interventions. In these studies, the simple finding of a significant, positiv...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.3109/10408444.2013.777688
更新日期:2013-01-01 00:00:00
abstract::Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in our environment and can cause cancer. Exposure to PAHs can be assessed by protein adduct dosimetry using benzo[a]pyrene (B[a]P) as a model compound. We present an overview of analytical methods to detect B[a]P- derived protein adducts in humans, their uses in e...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.3109/10408440903283633
更新日期:2010-01-01 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::There is controversy on whether occupational exposure to beryllium causes lung cancer. We conducted a systematic review of epidemiologic studies on cancer among workers exposed to beryllium, including a study of seven U.S. production plants which has been recently updated, a study of patients with beryllium disease (l...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.3109/10408444.2011.631898
更新日期:2012-02-01 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::Due to the rapid development of a diverse array of nanoparticles, used in a wide variety of products, there are now many international activities to assess the potential toxicity of these materials. These particles are developed due to properties such as catalytic reactivity, high surface area, light emission properti...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.1080/10408440903120975
更新日期:2009-01-01 00:00:00
abstract::Chemical DNA interaction and its processing can now be studied at the level of specific genomic regions. Such investigations have revealed important new information about the molecular biology of the cellular responses to genomic insult and especially of the repair processes. They also have demonstrated that both the ...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.3109/10408449409017921
更新日期:1994-01-01 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::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::This article provides a detailed assessment of the toxicological and pharmacological literature concerning alcohol-induced biphasic dose-response relationships. The assessment reveals that alcohol-induced hormetic-like dose-response relationships are commonly observed, highly generalizeable according to model and endp...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.1080/713611043
更新日期:2003-01-01 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::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::Oral absorption efficiency is an important factor to consider in human risk assessment and varies widely between elements. Linking absorption efficiency to chemical properties facilitates the understanding of underlying processes and enables extrapolation across elements. In our study, oral absorption efficiency in hu...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,meta分析
doi:10.3109/10408444.2013.813906
更新日期:2013-10-01 00:00:00
abstract::During the past 30 years, thousands of quantitative structure-activity relationships (QSAR) have been published for all sorts of chemicals acting on many forms of life or parts thereof (DNA, enzymes, organelles, etc.). Very little effort has been made to show the relationship among these equations. In this report, we ...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.3109/10408449509089887
更新日期:1995-01-01 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 insecticide diflubenzuron (DFB) is commonly used in various mid-Atlantic states for suppression of gypsy moths in hardwood forests. DFB is potentially toxic to nontarget biota because it can enter aquatic systems through aerial application or runoff after precipitation events. Based on this concern, the objectives...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.3109/10408449209145321
更新日期:1992-01-01 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::Although animal models cannot exactly replicate human psychiatric disorders, they may be useful to investigate whether the behaviors associated with certain exposures in animals parallel those observed in people. According to the most current version of the Diagnostic and Statistical Manual of Mental Disorders, autism...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.3109/10408444.2014.907772
更新日期:2014-07-01 00:00:00
abstract::The heme biosynthetic pathway is closely controlled by levels of the end product of the pathway, namely, heme, and porphyrins are normally formed in only trace amounts. When control mechanisms are disturbed by xenobiotics, porphyrins accumulate and serve as a signal of the interaction between a xenobiotic and the heme...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.3109/10408448509029323
更新日期:1985-01-01 00:00:00
abstract::In this review, an overview is presented of the current knowledge of genetic polymorphisms of four of the most important enzyme families involved in the metabolism of xenobiotics, that is, the N-acetyltransferase (NAT), cytochrome P450 (P450), glutathione-S-transferase (GST), and microsomal epoxide hydrolase (mEH) enz...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.1080/10408449991349186
更新日期:1999-01-01 00:00:00
abstract::In the late 1960s the artificial sweetener cyclamate was implicated as a bladder carcinogen in rats. This finding and other concerns about its safety ultimately led to a ban on cyclamate in the U.S. and restrictions on its use in many other countries. Since that time, the carcinogenic potential of cyclamate and cycloh...
journal_title:Critical reviews in toxicology
pub_type: 杂志文章,评审
doi:10.3109/10408448609037465
更新日期:1986-01-01 00:00:00