Modernizing the Bradford Hill criteria for assessing causal relationships in observational data.

Abstract:

:Perhaps no other topic in risk analysis is more difficult, more controversial, or more important to risk management policy analysts and decision-makers than how to draw valid, correctly qualified causal conclusions from observational data. Statistical methods can readily quantify associations between observed variables using measures such as relative risk (RR) ratios, odds ratios (OR), slope coefficients for exposure or treatment variables in regression models, and quantities derived from these measures. Textbooks of epidemiology explain how to calculate population attributable fractions, attributable risks, burden-of-disease estimates, and probabilities of causation from relative risk (RR) ratios. Despite their suggestive names, these association-based measures have no necessary connection to causation if the associations on which they are based arise from bias, confounding, p-hacking, coincident historical trends, or other noncausal sources. But policy analysts and decision makers need something more: trustworthy predictions - and, later, evaluations - of the changes in outcomes caused by changes in policy variables. This concept of manipulative causation differs from the more familiar concepts of associational and attributive causation most widely used in epidemiology. Drawing on modern literature on causal discovery and inference principles and algorithms for drawing limited but useful causal conclusions from observational data, we propose seven criteria for assessing consistency of data with a manipulative causal exposure-response relationship - mutual information, directed dependence, internal and external consistency, coherent causal explanation of biological plausibility, causal mediation confirmation, and refutation of non-causal explanations - and discuss to what extent it is now possible to automate discovery of manipulative causal dependencies and quantification of causal effects from observational data. We compare our proposed principles for causal discovery and inference to the traditional Bradford Hill considerations from 1965. Understanding how old and new principles are related can clarify and enrich both.

journal_name

Crit Rev Toxicol

authors

Cox LA Jr

doi

10.1080/10408444.2018.1518404

subject

Has Abstract

pub_date

2018-09-01 00:00:00

pages

682-712

issue

8

eissn

1040-8444

issn

1547-6898

journal_volume

48

pub_type

杂志文章
  • Beryllium and lung cancer: a weight of evidence evaluation of the toxicological and epidemiological literature.

    abstract::The potential carcinogenicity of beryllium has been a topic of study since the mid-1940s. Since then, numerous scientific and regulatory bodies have assigned beryllium to various categories with respect to its carcinogenicity. Past epidemiologic and animal studies, however, have been marked with notable methodological...

    journal_title:Critical reviews in toxicology

    pub_type: 杂志文章,评审

    doi:10.1080/10408440902837967

    authors: Hollins DM,McKinley MA,Williams C,Wiman A,Fillos D,Chapman PS,Madl AK

    更新日期:2009-01-01 00:00:00

  • Longitudinal relationships between lung cancer mortality rates, smoking, and ambient air quality: a comprehensive review and analysis.

    abstract::Lung cancer mortality (LCM) has been associated with smoking and air pollution. This article draws on smoking relationships to clarify air pollution relationships. We analyzed cohort and population-based smoking studies and identified effects of latency and cumulative exposures. We found cogent relationships through l...

    journal_title:Critical reviews in toxicology

    pub_type: 杂志文章,评审

    doi:10.1080/10408444.2019.1700210

    authors: Lipfert FW,Wyzga RE

    更新日期:2019-10-01 00:00:00

  • Pharmacokinetics and toxicity testing.

    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

    authors: Clark B,Smith DA

    更新日期:1984-01-01 00:00:00

  • Review of genotoxicity studies of glyphosate and glyphosate-based formulations.

    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

    authors: Kier LD,Kirkland DJ

    更新日期:2013-04-01 00:00:00

  • Impact of changes in human reproduction on the incidence of endocrine-related diseases.

    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

    authors: Swaen GMH,Boffetta P,Zeegers M

    更新日期:2018-10-01 00:00:00

  • Albumin and hemoglobin adducts of benzo[a]pyrene in humans--analytical methods, exposure assessment, and recommendations for future directions.

    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

    authors: Käfferlein HU,Marczynski B,Mensing T,Brüning T

    更新日期:2010-01-01 00:00:00

  • Ethanol and hormesis.

    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

    authors: Calabrese EJ,Baldwin LA

    更新日期:2003-01-01 00:00:00

  • Genotoxic activities of aniline and its metabolites and their relationship to the carcinogenicity of aniline in the spleen of rats.

    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

    authors: Bomhard EM,Herbold BA

    更新日期:2005-12-01 00:00:00

  • Interspecies comparisons of lung responses to inhaled particles and gases.

    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

    authors: Warheit DB

    更新日期:1989-01-01 00:00:00

  • Adenosine: biphasic dose responses.

    abstract::This article characterizes the occurrence of biphasic dose responses by adenosine and its stable analogs in numerous systems, including the respiratory tract, kidney, cardiovascular system, and brain. Considerable mechanistic research on various systems explored and clarified the interactions of the A-1 and A-2 recept...

    journal_title:Critical reviews in toxicology

    pub_type: 杂志文章,评审

    doi:10.1080/20014091111811

    authors: Calabrese EJ

    更新日期:2001-07-01 00:00:00

  • Hormetic responses in neural systems: consideration, contexts, and caveats.

    abstract::Dr. Edward Calabrese asserts that hormetic responses occur in neural systems, and provides ample review of evidence to support this claim. In this essay, we survey Dr. Calabrese's findings, illustrate the somewhat provocative premise of hormesis, and posit that while evidence suggests that amplification of low-dose ef...

    journal_title:Critical reviews in toxicology

    pub_type: 杂志文章

    doi:10.1080/10408440802026356

    authors: Giordano J,Ives JA,Jonas WB

    更新日期:2008-01-01 00:00:00

  • Endocrine-disrupting chemicals: prepubertal exposures and effects on sexual maturation and thyroid activity in the female rat. A focus on the EDSTAC recommendations.

    abstract::In 1996, the US Environmental Protection Agency was given a mandate by Congress to develop a screening program that would evaluate whether variously identified compounds could affect human health by mimicking or interfering with normal endocrine regulatory functions. Toward this end, the Agency chartered the Endocrine...

    journal_title:Critical reviews in toxicology

    pub_type: 杂志文章,评审

    doi:10.1080/10408440091159185

    authors: Goldman JM,Laws SC,Balchak SK,Cooper RL,Kavlock RJ

    更新日期:2000-03-01 00:00:00

  • Toxicological profile of lipid-based nanostructures: are they considered as completely safe nanocarriers?

    abstract::Nanoparticles are ubiquitous in the environment and are widely used in medical science (e.g. bioimaging, diagnosis, and drug therapy delivery). Due to unique physicochemical properties, they are able to cross many barriers, which is not possible for traditional drugs. Nevertheless, exposure to NPs and their following ...

    journal_title:Critical reviews in toxicology

    pub_type: 杂志文章,评审

    doi:10.1080/10408444.2020.1719974

    authors: Azarnezhad A,Samadian H,Jaymand M,Sobhani M,Ahmadi A

    更新日期:2020-02-01 00:00:00

  • Application of a novel integrated toxicity testing strategy incorporating "3R" principles of animal research to evaluate the safety of a new agrochemical sulfoxaflor.

    abstract::Plant protection products (PPPs) and the active substance(s) contained within them are rigorously and comprehensively tested prior to registration to ensure that human health is not impacted by their use. In recent years, there has been a widespread drive to have more relevant testing strategies (e.g., ILSI/HESI-ACSA ...

    journal_title:Critical reviews in toxicology

    pub_type: 杂志文章,评审

    doi:10.3109/10408444.2014.910753

    authors: Terry C,Rasoulpour RJ,Saghir S,Marty S,Gollapudi BB,Billington R

    更新日期:2014-05-01 00:00:00

  • Evolution of chemical-specific adjustment factors (CSAF) based on recent international experience; increasing utility and facilitating regulatory acceptance.

    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

    authors: Bhat VS,Meek MEB,Valcke M,English C,Boobis A,Brown R

    更新日期:2017-10-01 00:00:00

  • Validity of biomarkers in environmental health studies: the case of PAHs and benzene.

    abstract::Exposure biomarkers, which have long been restricted to the framework of occupational hygiene, currently arouse increasing interest in the field of environmental pollution. To assess their validity, we propose here a conceptual framework that is based on their intrinsic characteristics and on properties related to the...

    journal_title:Critical reviews in toxicology

    pub_type: 杂志文章,评审

    doi:10.1080/10408449991349195

    authors: Dor F,Dab W,Empereur-Bissonnet P,Zmirou D

    更新日期:1999-03-01 00:00:00

  • Risks and benefits of dietary isoflavones for cancer.

    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

    authors: Andres S,Abraham K,Appel KE,Lampen A

    更新日期:2011-07-01 00:00:00

  • Assessing cancer hazards of bitumen emissions - a case study for complex petroleum substances.

    abstract::When assessing cancer hazard and risk associated with a complex petroleum substance, like bitumen emissions, there are often conflicting results related to human, animal and mechanistic studies. Validation of the complex composition to assure that it matches real-world exposures and control of confounders are pivotal ...

    journal_title:Critical reviews in toxicology

    pub_type: 杂志文章,评审

    doi:10.1080/10408444.2017.1391170

    authors: Kriech AJ,Schreiner CA,Osborn LV,Riley AJ

    更新日期:2018-02-01 00:00:00

  • The estrogenic activity of resveratrol: a comprehensive review of in vitro and in vivo evidence and the potential for endocrine disruption.

    abstract::trans-Resveratrol, a polyphenolic stilbene of plant origin is structurally similar to natural and synthetic estrogens and has been classified a phytoestrogen. Direct binding of resveratrol to the nuclear estrogen receptor (ER) and modulation of its genomic activity was among the first of its reported pharmacological a...

    journal_title:Critical reviews in toxicology

    pub_type: 杂志文章,评审

    doi:10.1080/10408444.2020.1762538

    authors: Qasem RJ

    更新日期:2020-05-01 00:00:00

  • Potential pulmonary effects of man-made organic fiber (MMOF) dusts.

    abstract::In the first half of the twentieth century epidemiologic evidence linked elevated incidences of pulmonary fibrosis and cancer with inhalation of chrysotile and crocidolite asbestos, a family of naturally occurring inorganic fibrous materials. As the serpentine and amphibole forms of asbestos were phased out, synthetic...

    journal_title:Critical reviews in toxicology

    pub_type: 杂志文章,评审

    doi:10.1080/20014091111965

    authors: Warheit DB,Hart GA,Hesterberg TW,Collins JJ,Dyer WM,Swaen GM,Castranova V,Soiefer AI,Kennedy GL Jr

    更新日期:2001-11-01 00:00:00

  • Consequences of chemical impact of disinfectants: safe preventive measures against COVID-19.

    abstract::Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has created a significant threat to global health. It originated in Wuhan, China and caused a total of 83,483 confirmed cases and 4634 deaths until June 2020. This novel virus spread primarily through respiratory...

    journal_title:Critical reviews in toxicology

    pub_type: 杂志文章,评审

    doi:10.1080/10408444.2020.1790499

    authors: Rai NK,Ashok A,Akondi BR

    更新日期:2020-07-01 00:00:00

  • Comparative QSAR in toxicology: examples from teratology and cancer chemotherapy of aniline mustards.

    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

    authors: Hansch C,Telzer BR,Zhang L

    更新日期:1995-01-01 00:00:00

  • Proteinuria: changes and mechanisms in toxic nephropathies.

    abstract::During the last few decades, considerable progress has been made in the understanding of the pathophysiological mechanisms of proteinuria. A great variety of hemodynamic or biochemical mechanisms acting at different sites of the nephron have been shown to alter the renal handling and the urinary excretion of proteins....

    journal_title:Critical reviews in toxicology

    pub_type: 杂志文章,评审

    doi:10.3109/10408449109019572

    authors: Bernard A,Lauwerys RR

    更新日期:1991-01-01 00:00:00

  • Effects of atrazine on fish, amphibians, and reptiles: update of the analysis based on quantitative weight of evidence.

    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

    authors: Hanson ML,Solomon KR,Van Der Kraak GJ,Brian RA

    更新日期:2019-09-01 00:00:00

  • Genotoxicity Expert Panel review: weight of evidence evaluation of the genotoxicity of glyphosate, glyphosate-based formulations, and aminomethylphosphonic acid.

    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

    authors: Brusick D,Aardema M,Kier L,Kirkland D,Williams G

    更新日期:2016-09-01 00:00:00

  • Pharmacological enhancement of neuronal survival.

    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

    authors: Calabrese EJ

    更新日期:2008-01-01 00:00:00

  • Assessment of the carcinogenicity of the nonnutritive sweetener cyclamate.

    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

    authors: Ahmed FE,Thomas DB

    更新日期:1992-01-01 00:00:00

  • Gestational/perinatal chlorpyrifos exposure is not associated with autistic-like behaviors in rodents.

    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

    authors: Williams AL,DeSesso JM

    更新日期:2014-07-01 00:00:00

  • Aquatic insects and trace metals: bioavailability, bioaccumulation, and toxicity.

    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

    authors: Hare L

    更新日期:1992-01-01 00:00:00

  • Tumors of the mouse hematopoietic system: their diagnosis and interpretation in safety evaluation tests. Report of a study group.

    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

    authors: Wogan GN

    更新日期:1984-01-01 00:00:00