A Combined Morphometric and Statistical Approach to Assess Nonmonotonicity in the Developing Mammary Gland of Rats in the CLARITY-BPA Study.

Abstract:

BACKGROUND:The Consortium Linking Academic and Regulatory Insights on Bisphenol-A (CLARITY-BPA) is a rare collaboration of guideline-compliant (core) studies and academic hypothesis-based studies to assess the effects of bisphenol A (BPA). OBJECTIVES:We aimed to a) determine whether BPA showed effects on the developing rat mammary gland using new quantitative and established semiquantitative methods in two laboratories, b) develop a software tool for automatic evaluation of quantifiable aspects of the mammary ductal tree, and c) compare those methods. METHODS:Sprague-Dawley rats were exposed to BPA, vehicle, or positive control [ethinyl estradiol (EE2)] by oral gavage beginning on gestational day (GD)6 and continuing with direct dosing of the pups after birth. There were two studies: subchronic and chronic. The latter used two exposure regimes, one stopping at postnatal day (PND)21 (stop-dose) the other continuing until tissue harvest (continuous). Glands were harvested at multiple time points; whole mounts and histological specimens were analyzed blinded to treatment. RESULTS:The subchronic study's semiquantitative analysis revealed no significant differences between control and BPA dose groups at PND21, whereas at PND90 there were significant differences between control and the lowest BPA dose and between control and the lowest EE2 dose in animals in estrus. Quantitative, automatized analysis of the chronic PND21 specimens displayed nonmonotonic BPA effects, with a breaking point between the 25 and 250 μ g / kg body weight (BW) per day doses. This breaking point was confirmed by a global statistical analysis of chronic study animals at PND90 and 6 months analyzed by the quantitative method. The BPA response was different from the EE2 effect for many features. CONCLUSIONS:Both the semiquantitative and the quantitative methods revealed nonmonotonic effects of BPA. The quantitative unsupervised analysis used 91   measurements and produced the most striking nonmonotonic dose-response curves. At all time points, lower doses resulted in larger effects, consistent with the core study, which revealed a significant increase of mammary adenocarcinoma incidence in the stop-dose animals at the lowest BPA dose tested. https://doi.org/10.1289/EHP6301.

authors

Montévil M,Acevedo N,Schaeberle CM,Bharadwaj M,Fenton SE,Soto AM

doi

10.1289/EHP6301

subject

Has Abstract

pub_date

2020-05-01 00:00:00

pages

57001

issue

5

eissn

0091-6765

issn

1552-9924

journal_volume

128

pub_type

杂志文章
  • Total Effective Xenoestrogen Burden in Serum Samples and Risk for Breast Cancer in a Population-Based Multicase-Control Study in Spain.

    abstract:BACKGROUND:Most studies on endocrine-disrupting chemicals and breast cancer have focused on single compounds and have produced inconclusive findings. OBJECTIVES:We assessed the combined estrogenic effects of mixtures of xenoestrogens in serum and their relationship to breast cancer risk. METHODS:A total of 186 incide...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/EHP157

    authors: Pastor-Barriuso R,Fernández MF,Castaño-Vinyals G,Whelan D,Pérez-Gómez B,Llorca J,Villanueva CM,Guevara M,Molina-Molina JM,Artacho-Cordón F,Barriuso-Lapresa L,Tusquets I,Dierssen-Sotos T,Aragonés N,Olea N,Kogevinas M,Pollá

    更新日期:2016-10-01 00:00:00

  • Computer-assisted studies of molecular structure and genotoxic activity by pattern recognition techniques.

    abstract::Often a compound's biological activity is determined by complex relationships between its structural components. Such a relationship often can only be adequately described and exploited by multivariate structure-activity relationship (SAR) studies that can deal with many variables simultaneously. Pattern recognition (...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章,评审

    doi:10.1289/ehp.8561329

    authors: Stouch TR,Jurs PC

    更新日期:1985-09-01 00:00:00

  • Pyrethroid pesticide exposure and parental report of learning disability and attention deficit/hyperactivity disorder in U.S. children: NHANES 1999-2002.

    abstract:BACKGROUND:Use of pyrethroid insecticides has increased dramatically over the past decade; however, data on their potential health effects, particularly on children, are limited. OBJECTIVE:We examined the cross-sectional association between postnatal pyrethroid exposure and parental report of learning disability (LD) ...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.1308031

    authors: Quirós-Alcalá L,Mehta S,Eskenazi B

    更新日期:2014-12-01 00:00:00

  • Applications of physiologic pharmacokinetic modeling in carcinogenic risk assessment.

    abstract::The use of physiologically based pharmacokinetic (PBPK) models has been proposed as a means of estimating the dose of the reactive metabolites of carcinogenic xenobiotics reaching target tissues, thereby affording an opportunity to base estimates of potential cancer risk on tissue dose rather than external levels of e...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章,评审

    doi:10.1289/ehp.94102s1137

    authors: Krewski D,Withey JR,Ku LF,Andersen ME

    更新日期:1994-12-01 00:00:00

  • Cellular and humoral immune abnormalities in Gulf War veterans.

    abstract::We examined 100 symptomatic Gulf War veterans (patients) and 100 controls for immunologic assays. The veterans and controls were compared for the percentage of T cells (CD3); B cells (CD19); helper:suppressor (CD4:CD8) ratio; natural killer (NK) cell activity; mitogenic response to phytohemagglutin (PHA) and pokeweed ...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.6881

    authors: Vojdani A,Thrasher JD

    更新日期:2004-06-01 00:00:00

  • Dioxins and endometriosis: a plausible hypothesis.

    abstract::A potential connection exists between exposure to organochlorine chemicals and the increasing prevalence of endometriosis. Evidence shows that dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin) can increase the incidence and severity of the disease in monkeys and can promote the growth or survival of endometrial tissue impl...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章,评审

    doi:10.1289/ehp.0211015

    authors: Birnbaum LS,Cummings AM

    更新日期:2002-01-01 00:00:00

  • Serum dioxin concentrations and quality of ovarian function in women of Seveso.

    abstract:BACKGROUND:Although 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been associated with alterations in ovarian function and hormones in animals, it has not been studied in humans. On 10 July 1976, an explosion exposed residents of Seveso, Italy, to the highest levels of TCDD in a population. Twenty years later, we init...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.9667

    authors: Warner M,Eskenazi B,Olive DL,Samuels S,Quick-Miles S,Vercellini P,Gerthoux PM,Needham L,Patterson DG,Mocarelli P

    更新日期:2007-03-01 00:00:00

  • Assessing household solid fuel use: multiple implications for the Millennium Development Goals.

    abstract:OBJECTIVE:The World Health Organization is the agency responsible for reporting the Millennium Development Goal (MDG) indicator "percentage of population using solid fuels." In this article, we present the results of a comprehensive assessment of solid fuel use, conducted in 2005, and discuss the implications of our fi...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.8603

    authors: Rehfuess E,Mehta S,Prüss-Ustün A

    更新日期:2006-03-01 00:00:00

  • Colorectal Cancer and Long-Term Exposure to Trihalomethanes in Drinking Water: A Multicenter Case-Control Study in Spain and Italy.

    abstract:BACKGROUND:Evidence on the association between colorectal cancer and exposure to disinfection by-products in drinking water is inconsistent. OBJECTIVES:We assessed long-term exposure to trihalomethanes (THMs), the most prevalent group of chlorination by-products, to evaluate the association with colorectal cancer. ME...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章,多中心研究

    doi:10.1289/EHP155

    authors: Villanueva CM,Gracia-Lavedan E,Bosetti C,Righi E,Molina AJ,Martín V,Boldo E,Aragonés N,Perez-Gomez B,Pollan M,Acebo IG,Altzibar JM,Zabala AJ,Ardanaz E,Peiró R,Tardón A,Chirlaque MD,Tavani A,Polesel J,Serraino D,Pi

    更新日期:2017-01-01 00:00:00

  • Cancer incidence in world trade center rescue and recovery workers, 2001-2008.

    abstract:BACKGROUND:World Trade Center (WTC) rescue and recovery workers were exposed to a complex mix of pollutants and carcinogens. OBJECTIVE:The purpose of this investigation was to evaluate cancer incidence in responders during the first 7 years after 11 September 2001. METHODS:Cancers among 20,984 consented participants ...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.1205894

    authors: Solan S,Wallenstein S,Shapiro M,Teitelbaum SL,Stevenson L,Kochman A,Kaplan J,Dellenbaugh C,Kahn A,Biro FN,Crane M,Crowley L,Gabrilove J,Gonsalves L,Harrison D,Herbert R,Luft B,Markowitz SB,Moline J,Niu X,Sacks H,

    更新日期:2013-06-01 00:00:00

  • Bacterial mutagenicity of pyrolysis tars produced from chloro-organic fuels.

    abstract::Droplets of toluene and three chlorinated organics, ortho-dichlorobenzene, 1,2-dichloroethane, and trichloroethylene, were pyrolyzed in pure nitrogen. The composition and bacterial mutagenicity of the product tars were measured. The presence of organic chlorine was found to affect both pyrolysis product tar compositio...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.94102s1283

    authors: Mulholland JA,Sarofim AF,Longwell JP,Lafleur AL,Thilly WG

    更新日期:1994-01-01 00:00:00

  • Is it worth a dam?

    abstract::Once a sign of modernization and growth, dams are often seen today as symbols of environmental and social devastation. Over 800,000 dams have been built worldwide to provide drinking water, flood control, hydropower, irrigation, navigation, and water storage. Dams do indeed provide these things,but at the cost of seve...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.971051050

    authors: Joyce S

    更新日期:1997-10-01 00:00:00

  • Residential Exposure to Natural Background Radiation and Risk of Childhood Acute Leukemia in France, 1990-2009.

    abstract:BACKGROUND:Exposures to high-dose ionizing radiation and high-dose rate ionizing radiation are established risk factors for childhood acute leukemia (AL). The risk of AL following exposure to lower doses due to natural background radiation (NBR) has yet to be conclusively determined. METHODS:AL cases diagnosed over 19...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/EHP296

    authors: Demoury C,Marquant F,Ielsch G,Goujon S,Debayle C,Faure L,Coste A,Laurent O,Guillevic J,Laurier D,Hémon D,Clavel J

    更新日期:2017-04-01 00:00:00

  • Influence of exogenous estrogen receptor ligands on uterine leiomyoma: evidence from an in vitro/in vivo animal model for uterine fibroids.

    abstract::The remarkable frequency of uterine leiomyoma in the human population calls into question the potential for the participation of environmental factors in tumor etiology. Having been implicated in the dramatic rise in hormone-related cancers in recent years, endocrine disruptors are salient suspects in this pathogenesi...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章,评审

    doi:10.1289/ehp.00108s5829

    authors: Hunter DS,Hodges LC,Eagon PK,Vonier PM,Fuchs-Young R,Bergerson JS,Walker CL

    更新日期:2000-10-01 00:00:00

  • Genomic and proteomic profiling of responses to toxic metals in human lung cells.

    abstract::Examining global effects of toxic metals on gene expression can be useful for elucidating patterns of biological response, discovering underlying mechanisms of toxicity, and identifying candidate metal-specific genetic markers of exposure and response. Using a 1,200 gene nylon array, we examined changes in gene expres...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.111-1241504

    authors: Andrew AS,Warren AJ,Barchowsky A,Temple KA,Klei L,Soucy NV,O'Hara KA,Hamilton JW

    更新日期:2003-05-01 00:00:00

  • Personalized exposure assessment: promising approaches for human environmental health research.

    abstract::New technologies and methods for assessing human exposure to chemicals, dietary and lifestyle factors, infectious agents, and other stressors provide an opportunity to extend the range of human health investigations and advance our understanding of the relationship between environmental exposure and disease. An ad hoc...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章,评审

    doi:10.1289/ehp.7651

    authors: Weis BK,Balshaw D,Barr JR,Brown D,Ellisman M,Lioy P,Omenn G,Potter JD,Smith MT,Sohn L,Suk WA,Sumner S,Swenberg J,Walt DR,Watkins S,Thompson C,Wilson SH

    更新日期:2005-07-01 00:00:00

  • Impact of reduced maternal exposures to wood smoke from an introduced chimney stove on newborn birth weight in rural Guatemala.

    abstract:BACKGROUND:A growing body of evidence indicates a relationship between household indoor air pollution from cooking fires and adverse neonatal outcomes, such as low birth weight (LBW), in resource-poor countries. OBJECTIVE:We examined the effect of reduced wood smoke exposure in pregnancy on LBW of Guatemalan infants i...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章,随机对照试验

    doi:10.1289/ehp.1002928

    authors: Thompson LM,Bruce N,Eskenazi B,Diaz A,Pope D,Smith KR

    更新日期:2011-10-01 00:00:00

  • Interaction of asbestos with metaplastic squamous epithelium developing in organ cultures of hamster trachea.

    abstract::The normal mucociliary epithelium of the respiratory tract in chronic cigarette smokers often is replaced focally by a metaplastic squamous epithelium. Because asbestos workers who smoke have a substantially greater risk of bronchogenic carcinoma than nonsmokers, we hypothesized that interaction of asbestos with squam...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.835127

    authors: Woodworth CD,Mossman BT,Craighead JE

    更新日期:1983-09-01 00:00:00

  • Status of marine biomedical research.

    abstract::A meeting on Marine Biomedical Research, sponsored by the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health and the Smithsonian Institution Museum of Natural History, was attended by approximately 125 scientists, directors and representatives from many of the country's marine b...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.7613147

    authors: Bessey O

    更新日期:1976-02-01 00:00:00

  • The Prevalence and Use of Walking Loops in Neighborhood Parks: A National Study.

    abstract:BACKGROUND:Previous studies indicate that the design of streets and sidewalks can influence physical activity among residents. Park features also influence park use and park-based physical activity. Although individuals can walk on streets and sidewalks, walking loops in parks offer a setting to walk in nature and to a...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/EHP293

    authors: Cohen DA,Han B,Evenson KR,Nagel C,McKenzie TL,Marsh T,Williamson S,Harnik P

    更新日期:2017-02-01 00:00:00

  • Local variations in CO and particulate air pollution and adverse birth outcomes in Los Angeles County, California, USA.

    abstract::We extended our previous analyses of term low birth weight (LBW) and preterm birth to 1994-2000, a period of declining air pollution levels in the South Coast Air Basin. We speculated that the effects we observed previously for carbon monoxide, particulate matter < 10 microm in aerodynamic diameter (PM10), and traffic...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.7751

    authors: Wilhelm M,Ritz B

    更新日期:2005-09-01 00:00:00

  • Thyroid-hormone-disrupting chemicals: evidence for dose-dependent additivity or synergism.

    abstract::Endocrine disruption from environmental contaminants has been linked to a broad spectrum of adverse outcomes. One concern about endocrine-disrupting xenobiotics is the potential for additive or synergistic (i.e., greater-than-additive) effects of mixtures. A short-term dosing model to examine the effects of environmen...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.8195

    authors: Crofton KM,Craft ES,Hedge JM,Gennings C,Simmons JE,Carchman RA,Carter WH Jr,DeVito MJ

    更新日期:2005-11-01 00:00:00

  • A Bayesian hierarchical approach for relating PM(2.5) exposure to cardiovascular mortality in North Carolina.

    abstract::Considerable attention has been given to the relationship between levels of fine particulate matter (particulate matter < or = 2.5 microm in aerodynamic diameter; PM(2.5) in the atmosphere and health effects in human populations. Since the U.S. Environmental Protection Agency began widespread monitoring of PM(2.5) lev...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.6980

    authors: Holloman CH,Bortnick SM,Morara M,Strauss WJ,Calder CA

    更新日期:2004-09-01 00:00:00

  • Operant methodology in the study of learning.

    abstract::A series of experiments is described in which operant methodology is used to study the effects of drugs on "learning." Emphasis is placed on the technique of repeated acquisition as a behavioral baseline for studying this type of transition state. In this technique, each subject is required to learn a new discriminati...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.782677

    authors: Thompson DM,Moerschbaecher JM

    更新日期:1978-10-01 00:00:00

  • DNA damage-inducible genes as biomarkers for exposures to environmental agents.

    abstract::A biodosimetric approach to determine alpha-particle dose to the respiratory tract epithelium from known exposures to radon has been developed in the rat. Cytotoxicity assays have been used to obtain dose-conversion factors for cumulative exposures typical of those encountered by underground uranium miners. However, t...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.97105s4913

    authors: Johnson NF,Carpenter TR,Jaramillo RJ,Liberati TA

    更新日期:1997-06-01 00:00:00

  • The relationship between blood lead, blood pressure, stroke, and heart attacks in middle-aged British men.

    abstract::The relationship between blood lead concentration and blood pressure is examined in a survey of 7371 men aged 40 to 59 from 24 British towns. After allowance for relevant confounding variables, including town of residence and alcohol consumption, there exists a very weak but statistically significant positive associat...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.887823

    authors: Pocock SJ,Shaper AG,Ashby D,Delves HT,Clayton BE

    更新日期:1988-06-01 00:00:00

  • Criteria air pollutants and toxic air pollutants.

    abstract::This review presents a brief overview of the health effects and exposures of two criteria pollutants--ozone and particulate matter--and two toxic air pollutants--benzene and formaldehyde. These pollutants were selected from the six criteria pollutants and from the 189 toxic air pollutants on the basis of their prevale...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章,评审

    doi:10.1289/ehp.00108s4625

    authors: Suh HH,Bahadori T,Vallarino J,Spengler JD

    更新日期:2000-08-01 00:00:00

  • Residential Road Traffic Noise and High Depressive Symptoms after Five Years of Follow-up: Results from the Heinz Nixdorf Recall Study.

    abstract:BACKGROUND:Traffic noise affects a large number of people, particularly in urbanized areas. Noise causes stress and annoyance, but less is known about the relationship between noise and depression. OBJECTIVE:We investigated the association of residential road traffic noise with depressive symptoms using 5-year follow-...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.1409400

    authors: Orban E,McDonald K,Sutcliffe R,Hoffmann B,Fuks KB,Dragano N,Viehmann A,Erbel R,Jöckel KH,Pundt N,Moebus S

    更新日期:2016-05-01 00:00:00

  • Hypochlorous acid-activated carbon: an oxidizing agent capable of producing hydroxylated polychlorinated biphenyls.

    abstract::Granular activated carbon (GAC), in the presence of dilute aqueous hypochlorite solutions typical of those used in water treatment, was converted to a reagent capable of carrying out free-radical coupling reactions and other oxidations of dilute aqueous solutions of phenols. The products included biphenyls with chlori...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.866997

    authors: Voudrias EA,Larson RA,Snoeyink VL,Chen AS,Stapleton PL

    更新日期:1986-11-01 00:00:00

  • Bioavailability of biologically detoxified lead: risks arising from consumption of polluted mussels.

    abstract::The possible risk for human health arising from consumption of lead-polluted shellfish was suggested by experiments on the bioavailability for mice of a "biologically detoxified" form of the metal. In this work, young mice were fed with a mixed diet including mussels collected in a Pb-polluted area. Metal concentratio...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.94102s3335

    authors: Regoli F,Orlando E

    更新日期:1994-09-01 00:00:00