Scaling basic toxicokinetic parameters from rat to man.

Abstract:

:Scaling of the quantified dispositional parameters of xenobiotics from animals to man is of interest from the standpoint of toxicology (e.g., poisoning and risk assessment). Scaling is also important from the standpoint of therapeutics because it represents a strategy for predicting first-use-in-human doses in clinical trials of investigational new drugs. Current strategies for scaling either doses of xenobiotics or the dispositional parameters of xenobiotics from animals to man rely on models that take account principally of species differences in weight or body surface area. Interspecies scaling of dispositional parameters such as clearance or volume of distribution commonly involves the comparison of estimates of these parameters for a given xenobiotic among numerous species on the basis of weight with the resultant mathematical relationship used to predict the values of those parameters for that xenobiotic in a species weighing, on average, about 70 kg (i.e., a man). Our approach has been to ascertain whether a useful mathematical model could be developed for predicting the dispositional parameters of a xenobiotic, its half-life and volume of distribution, in humans based exclusively on estimates of those parameters in rats. Based on a data set of about 100 different xenobiotics, we found that values for half-life and volume of distribution of a xenobiotic in humans can be predicted from the estimates of those parameters in rats.

authors

Bachmann K,Pardoe D,White D

doi

10.1289/ehp.96104400

subject

Has Abstract

pub_date

1996-04-01 00:00:00

pages

400-7

issue

4

eissn

0091-6765

issn

1552-9924

journal_volume

104

pub_type

杂志文章,评审
  • A cross-sectional investigation of chronic exposure to microcystin in relationship to childhood liver damage in the Three Gorges Reservoir Region, China.

    abstract:BACKGROUND:Microcystin-producing Microcystis bloom is a severe water problem in the world. Some reports indicate that chronic exposure to microcystin may result in liver damage in adults, but information on effects in children is limited. OBJECTIVE:We investigated the relationship between microcystin exposure and live...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.1002412

    authors: Li Y,Chen JA,Zhao Q,Pu C,Qiu Z,Zhang R,Shu W

    更新日期:2011-10-01 00:00:00

  • Benzene adducts with rat nucleic acids and proteins: dose-response relationship after treatment in vivo.

    abstract::The dose-response relationship of the benzene covalent interaction with biological macromolecules from rat organs was studied. The administered dose range was 3.6 x 10(7) starting from the highest dosage employed, 486 mg/kg, which is oncogenic for rodents, and included low and very low dosages. The present study was i...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.8982259

    authors: Mazzullo M,Bartoli S,Bonora B,Colacci A,Grilli S,Lattanzi G,Niero A,Turina MP,Parodi S

    更新日期:1989-07-01 00:00:00

  • Exogenous and endogenous determinants of blood trihalomethane levels after showering.

    abstract:BACKGROUND:We previously conducted a study to assess whether household exposures to tap water increased an individual's internal dose of trihalomethanes (THMs). Increases in blood THM levels among subjects who showered or bathed were variable, with increased levels tending to cluster in two groups. OBJECTIVES:Our goal...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.10049

    authors: Backer LC,Lan Q,Blount BC,Nuckols JR,Branch R,Lyu CW,Kieszak SM,Brinkman MC,Gordon SM,Flanders WD,Romkes M,Cantor KP

    更新日期:2008-01-01 00:00:00

  • Risk of benzene-induced leukemia predicted from the Pliofilm cohort.

    abstract::This report updates the risk assessment by Crump and Allen for benzene-induced leukemia that was based on a cohort exposed to benzene in the manufacture of Pliofilm. The present study derives new risk estimates using data from follow-up through 1987 (whereas the earlier assessment only had follow-up available through ...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.961041437

    authors: Crump KS

    更新日期:1996-12-01 00:00:00

  • Penetration of chemicals into the oocyte, uterine fluid, and preimplantation blastocyst.

    abstract::Chemicals, including commonly used drugs (e.g., penicillin, meprobamate, pyridium, and mercaptomerin) penetrate and persist for some time in the ovarian follicular fluid at concentrations approximately similar to that of the serum. Information as to the penetration of chemicals into the granulosa cells and into the oo...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.782425

    authors: Fabro S

    更新日期:1978-06-01 00:00:00

  • Pavlovian conditioning and multiple chemical sensitivity.

    abstract::Pavlovian conditioning processes may contribute to some symptoms of multiple chemical sensitivity (MCS). This review summarizes the potential relevance of the literature on conditional taste and olfactory aversions, conditional sensitization, and conditional immunomodulation to understanding MCS. A conditioning-based ...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章,评审

    doi:10.1289/ehp.97105s2521

    authors: Siegel S,Kreutzer R

    更新日期:1997-03-01 00:00:00

  • Aflatoxin contamination of commercial maize products during an outbreak of acute aflatoxicosis in eastern and central Kenya.

    abstract::In April 2004, one of the largest aflatoxicosis outbreaks occurred in rural Kenya, resulting in 317 cases and 125 deaths. Aflatoxin-contaminated homegrown maize was the source of the outbreak, but the extent of regional contamination and status of maize in commercial markets (market maize) were unknown. We conducted a...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.7998

    authors: Lewis L,Onsongo M,Njapau H,Schurz-Rogers H,Luber G,Kieszak S,Nyamongo J,Backer L,Dahiye AM,Misore A,DeCock K,Rubin C,Kenya Aflatoxicosis Investigation Group.

    更新日期:2005-12-01 00:00:00

  • Role of TET Dioxygenases and DNA Hydroxymethylation in Bisphenols-Stimulated Proliferation of Breast Cancer Cells.

    abstract:BACKGROUND:Bisphenol A (BPA), a ubiquitous environmental endocrine disruptor targeting estrogen receptors (ERs), has been implicated in the promotion of breast cancer. Perinatal exposure of BPA could induce longitudinal alteration of DNA hydroxymethylation in imprinted loci of mouse blood cells. To date, no data has be...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/EHP5862

    authors: Li Z,Lyu C,Ren Y,Wang H

    更新日期:2020-02-01 00:00:00

  • Follow-up screening of lead-poisoned children near an auto battery recycling plant, Haina, Dominican Republic.

    abstract::In August 1997 we performed a follow-up survey of 146 lead-poisoned children from a community near a previously active auto battery recycling smelter in Haina near Santo Domingo, Dominican Republic. Our follow-up survey confirmed a severe incidence of elevated blood lead (BPb) and erythrocyte protoporphyrin/zinc proto...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.99107917

    authors: Kaul B,Sandhu RS,Depratt C,Reyes F

    更新日期:1999-11-01 00:00:00

  • Modification of the interleukin-6 response to air pollution by interleukin-6 and fibrinogen polymorphisms.

    abstract:BACKGROUND:Evidence suggests that cardiovascular effects of air pollution are mediated by inflammation and that air pollution can induce genetic expression of the interleukin-6 gene (IL6). OBJECTIVES:We investigated whether IL6 and fibrinogen gene variants can affect plasma IL-6 responses to air pollution in patients ...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.0800370

    authors: Ljungman P,Bellander T,Schneider A,Breitner S,Forastiere F,Hampel R,Illig T,Jacquemin B,Katsouyanni K,von Klot S,Koenig W,Lanki T,Nyberg F,Pekkanen J,Pistelli R,Pitsavos C,Rosenqvist M,Sunyer J,Peters A

    更新日期:2009-09-01 00:00:00

  • Evaluation of the effectiveness of mass screening for uterine cancer in Japan: the potential years of life lost.

    abstract::To evaluate the effectiveness of mass screening for uterine cancer in Japan, we compared the changes in the age-adjusted rates of potential years of life lost (PYLL) due to uterine cancer between 1969 and 1972 to 1973 through 1977 between the high coverage-rate (intensively screened) areas and the comparable control a...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.908751

    authors: Kuroishi T,Hirose K,Tominaga S

    更新日期:1990-07-01 00:00:00

  • Lessons from Toxicology: Developing a 21st-Century Paradigm for Medical Research.

    abstract::Biomedical developments in the 21st century provide an unprecedented opportunity to gain a dynamic systems-level and human-specific understanding of the causes and pathophysiologies of disease. This understanding is a vital need, in view of continuing failures in health research, drug discovery, and clinical translati...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.1510345

    authors: Langley G,Austin CP,Balapure AK,Birnbaum LS,Bucher JR,Fentem J,Fitzpatrick SC,Fowle JR 3rd,Kavlock RJ,Kitano H,Lidbury BA,Muotri AR,Peng SQ,Sakharov D,Seidle T,Trez T,Tonevitsky A,van de Stolpe A,Whelan M,Willett C

    更新日期:2015-11-01 00:00:00

  • Let the "A" in WASH Stand for Air: Integrating Research and Interventions to Improve Household Air Pollution (HAP) and Water, Sanitation and Hygiene (WaSH) in Low-Income Settings.

    abstract:BACKGROUND:Research often suffers from overspecialization, a practice nurtured in academia and reinforced by funders. Indeed, investigators in household air pollution (HAP) and water, sanitation and hygiene (WaSH), working in poor parts of the world, rarely interact despite having similar training and using similar met...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/EHP4752

    authors: Clasen T,Smith KR

    更新日期:2019-02-01 00:00:00

  • Long-term traffic-related exposures and asthma onset in schoolchildren in oslo, norway.

    abstract:BACKGROUND:Whether there is a causal relation between long-term exposure to traffic and asthma development is so far not clear. This may be explained by inaccurate exposure assessment. OBJECTIVE:We investigated the associations of long-term traffic-related exposures with asthma onset assessed retrospectively and respi...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.11491

    authors: Oftedal B,Nystad W,Brunekreef B,Nafstad P

    更新日期:2009-05-01 00:00:00

  • Unventilated indoor coal-fired stoves in Guizhou province, China: reduction of arsenic exposure through behavior changes resulting from mitigation and health education in populations with arsenicosis.

    abstract::We report the results of a coordinated mitigation effort aimed at reducing arsenic (As) exposure in three counties of Guizhou province, China. Mitigation occurred in 2005 and encompassed 21 villages with 47,000 inhabitants, who were exposed to high levels of As in their diet through consumption of As-contaminated chil...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.9273

    authors: An D,Li D,Liang Y,Jing Z

    更新日期:2007-04-01 00:00:00

  • Behavioral alterations in response to fear-provoking stimuli and tranylcypromine induced by perinatal exposure to bisphenol A and nonylphenol in male rats.

    abstract::The purpose of this study was to examine whether perinatal exposure to two major environmental endocrine-disrupting chemicals, bisphenol A (BPA; 0.1 mg/kg/day orally) and nonylphenol [NP; 0.1 mg/kg/day (low dose) and 10 mg/kg/day (high dose) orally] daily from gestational day 3 to postnatal day 20 (transplacental and ...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.6961

    authors: Negishi T,Kawasaki K,Suzaki S,Maeda H,Ishii Y,Kyuwa S,Kuroda Y,Yoshikawa Y

    更新日期:2004-08-01 00:00:00

  • The effect of fine and coarse particulate air pollution on mortality: a national analysis.

    abstract:BACKGROUND:Although many studies have examined the effects of air pollution on mortality, data limitations have resulted in fewer studies of both particulate matter with an aerodynamic diameter of 2.5 and < 10 mi...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.0800108

    authors: Zanobetti A,Schwartz J

    更新日期:2009-06-01 00:00:00

  • Efficient elimination of inhaled nanoparticles from the alveolar region: evidence for interstitial uptake and subsequent reentrainment onto airways epithelium.

    abstract:BACKGROUND:There is ongoing discussion that inhaled nanoparticles (NPs, < 100 nm) may translocate from epithelial deposition sites of the lungs to systemic circulation. OBJECTIVES AND METHODS:We studied the disappearance of NPs from the epithelium by sequential lung retention and clearance and bronchoalveolar lavage (...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.9685

    authors: Semmler-Behnke M,Takenaka S,Fertsch S,Wenk A,Seitz J,Mayer P,Oberdörster G,Kreyling WG

    更新日期:2007-05-01 00:00:00

  • Indications of repair of radon-induced chromosome damage in human lymphocytes: an adaptive response induced by low doses of X-rays.

    abstract::Naturally occurring radon is a relatively ubiquitous environmental carcinogen to which large numbers of people can be exposed over their lifetimes. The accumulation of radon in homes, therefore, has led to a large program to determine the effects of the densely ionizing alpha particles that are produced when radon dec...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.93101s373

    authors: Wolff S,Afzal V,Jostes RF,Wiencke JK

    更新日期:1993-10-01 00:00:00

  • Examination of the safety of pediatric vaccine schedules in a non-human primate model: assessments of neurodevelopment, learning, and social behavior.

    abstract:BACKGROUND:In the 1990s, the mercury-based preservative thimerosal was used in most pediatric vaccines. Although there are currently only two thimerosal-containing vaccines (TCVs) recommended for pediatric use, parental perceptions that vaccines pose safety concerns are affecting vaccination rates, particularly in ligh...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.1408257

    authors: Curtis B,Liberato N,Rulien M,Morrisroe K,Kenney C,Yutuc V,Ferrier C,Marti CN,Mandell D,Burbacher TM,Sackett GP,Hewitson L

    更新日期:2015-06-01 00:00:00

  • Effects of sex hormones on oncogene expression in the vagina and on development of sexual dimorphism of the pelvis and anococcygeus muscle in the mouse.

    abstract::Neonatal treatment of female mice with diethystilbestrol (DES) is known to induce ovary-independent persistent proliferation and cornification of vaginal epithelium. This irreversibly changed vaginal epithelium persistently expressed higher levels of c-jun and c-fos mRNAs, which was not altered by postpubertal estroge...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章,评审

    doi:10.1289/ehp.95103s779

    authors: Iguchi T,Fukazawa Y,Bern HA

    更新日期:1995-10-01 00:00:00

  • Association between manganese exposure through drinking water and infant mortality in Bangladesh.

    abstract:BACKGROUND:Manganese is a common natural contaminant of groundwater in Bangladesh. In this cross-sectional study we assessed the association between water manganese and all-cause infant mortality in the offspring of female participants in the Health Effects of Arsenic Longitudinal Study Cohort. METHODS:In 2001, drinki...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.10051

    authors: Hafeman D,Factor-Litvak P,Cheng Z,van Geen A,Ahsan H

    更新日期:2007-07-01 00:00:00

  • Ultramorphological sperm characteristics in the risk assessment of health effects after radiation exposure among salvage workers in Chernobyl.

    abstract::We present a pilot study of individuals (liquidators) who were engaged in clean-up operations after the disaster at the nuclear power plant at Chernobyl in Ukraine. In the 10 years since the disaster, adverse health effects among exposed individuals have not been clearly defined. There is widespread fear of damage to ...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.97105s61445

    authors: Fischbein A,Zabludovsky N,Eltes F,Grischenko V,Bartoov B

    更新日期:1997-12-01 00:00:00

  • Long isoforms of NRF1 contribute to arsenic-induced antioxidant response in human keratinocytes.

    abstract:BACKGROUND:Human exposure to inorganic arsenic (iAs), a potent oxidative stressor, causes various dermal disorders, including hyperkeratosis and skin cancer. Nuclear factor-erythroid 2-related factor 1 (NRF1, also called NFE2L1) plays a critical role in regulating the expression of many antioxidant response element (AR...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.1002304

    authors: Zhao R,Hou Y,Xue P,Woods CG,Fu J,Feng B,Guan D,Sun G,Chan JY,Waalkes MP,Andersen ME,Pi J

    更新日期:2011-01-01 00:00:00

  • Intercomparison of analytical methods for arsenic speciation in human urine.

    abstract::An intercomparison exercise was conducted for the quantification of arsenic species in spiked human urine. The primary objective of the exercise was to determine the variance among laboratories in the analysis of arsenic species such as inorganic As (As+3 and As+5), monomethylarsonic acid (MMA), and dimethylarsinic ac...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.97105650

    authors: Crecelius E,Yager J

    更新日期:1997-06-01 00:00:00

  • Myeloid leukemia after hematotoxins.

    abstract::One of the most serious consequences of cancer therapy is the development of a second cancer, especially leukemia. Several distinct subsets of therapy-related leukemia can now be distinguished. Classic therapy-related myeloid leukemia typically occurs 5 to 7 years after exposure to alkylating agents and/or irradiation...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章,评审

    doi:10.1289/ehp.961041303

    authors: Larson RA,LeBeau MM,Vardiman JW,Rowley JD

    更新日期:1996-12-01 00:00:00

  • Outdoor particulate matter exposure and lung cancer: a systematic review and meta-analysis.

    abstract:BACKGROUND:Particulate matter (PM) in outdoor air pollution was recently designated a Group I carcinogen by the International Agency for Research on Cancer (IARC). This determination was based on the evidence regarding the relationship of PM2.5 and PM10 to lung cancer risk; however, the IARC evaluation did not include ...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章,meta分析,评审

    doi:10.1289/ehp/1408092

    authors: Hamra GB,Guha N,Cohen A,Laden F,Raaschou-Nielsen O,Samet JM,Vineis P,Forastiere F,Saldiva P,Yorifuji T,Loomis D

    更新日期:2014-09-01 00:00:00

  • Exposure of remote maritime populations to coplanar PCBs.

    abstract::Two remote maritime populations were evaluated for their biological exposure to organochlorines in 1989-1990. Because of their high intake of seafood, these two populations have high biological levels. One hundred nine breast milk samples from Inuit women from Arctic Québec were analyzed to determine levels of polychl...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.94102s1205

    authors: Dewailly E,Ryan JJ,Laliberté C,Bruneau S,Weber JP,Gingras S,Carrier G

    更新日期:1994-01-01 00:00:00

  • DNA adducts in peripheral blood lymphocytes from aluminum production plant workers determined by 32P-postlabeling and enzyme-linked immunosorbent assay.

    abstract::32P-Postlabeling analysis and enzyme-linked immunosorbent assay (ELISA) have been used to detect DNA adducts in peripheral blood lymphocytes from primary aluminum production plant workers who were exposed occupationally to a mixture of polycyclic aromatic hydrocarbons (PAHs). Preliminary results reported here are from...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.9399307

    authors: Schoket B,Phillips DH,Poirier MC,Vincze I

    更新日期:1993-03-01 00:00:00

  • Impatiens pollen germination and tube growth as a bioassay for toxic substances.

    abstract::Pollen of Impatiens sultanii Hook F. germinates and forms tubes rapidly at 25 degrees C in a simple medium containing 111.0 ppm CaCl2, 13.6 ppm KH2PO4, and 1000 ppm boric acid. Calcium, potassium, and boron are essential for germination and tube growth, but sucrose is not required. Pollen tubes grow with equal rapidit...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.813795

    authors: Bilderback DE

    更新日期:1981-01-01 00:00:00