Abstract:
:We review pharmacokinetic and pharmacodynamic factors that should be considered in the design and interpretation of developmental neurotoxicity studies. Toxicologic effects on the developing nervous system depend on the delivered dose, exposure duration, and developmental stage at which exposure occurred. Several pharmacokinetic processes (absorption, distribution, metabolism, and excretion) govern chemical disposition within the dam and the nervous system of the offspring. In addition, unique physical features such as the presence or absence of a placental barrier and the gradual development of the blood--brain barrier influence chemical disposition and thus modulate developmental neurotoxicity. Neonatal exposure may depend on maternal pharmacokinetic processes and transfer of the xenobiotic through the milk, although direct exposure may occur through other routes (e.g., inhalation). Measurement of the xenobiotic in milk and evaluation of biomarkers of exposure or effect following exposure can confirm or characterize neonatal exposure. Physiologically based pharmacokinetic and pharmacodynamic models that incorporate these and other determinants can estimate tissue dose and biologic response following in utero or neonatal exposure. These models can characterize dose--response relationships and improve extrapolation of results from animal studies to humans. In addition, pharmacologic data allow an experimenter to determine whether exposure to the test chemical is adequate, whether exposure occurs during critical periods of nervous system development, whether route and duration of exposure are appropriate, and whether developmental neurotoxicity can be differentiated from direct actions of the xenobiotic.
journal_name
Environ Health Perspectjournal_title
Environmental health perspectivesauthors
Dorman DC,Allen SL,Byczkowski JZ,Claudio L,Fisher JE Jr,Fisher JW,Harry GJ,Li AA,Makris SL,Padilla S,Sultatos LG,Mileson BEdoi
10.1289/ehp.01109s1101subject
Has Abstractpub_date
2001-03-01 00:00:00pages
101-11eissn
0091-6765issn
1552-9924pii
sc271_5_1835journal_volume
109 Suppl 1pub_type
杂志文章,评审abstract:BACKGROUND:Organophosphate developmental neurotoxicity involves multiple mechanisms converging on neural cell replication and differentiation. OBJECTIVES:We evaluated mechanisms contributing to the adverse effects of chlorpyrifos (CPF) on DNA synthesis, cell number and size, and cell signaling mediated by adenylyl cyc...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.10194
更新日期:2007-09-01 00:00:00
abstract::In vivo bone lead measurement using K X-ray fluorescence (KXRF) has been used to estimate long-term lead exposure, especially in adults. Relatively few studies have been conducted on young subjects with this technique. To explore the measurement variability of KXRF bone lead measurements in young subjects, the tibiae ...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.00108239
更新日期:2000-03-01 00:00:00
abstract:BACKGROUND:Tungsten carbide nanoparticles are being explored for their use in the manufacture of hard metals. To develop nanoparticles for broad applications, potential risks to human health and the environment should be evaluated and taken into consideration. OBJECTIVE:We aimed to assess the toxicity of well-characte...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.0800121
更新日期:2009-04-01 00:00:00
abstract::This study was undertaken to explore the effects of chronic low-level cadmium ingestion in Dahl hypertension-resistant (R) and hypertension-sensitive (S) lines of rats. Groups of weanling female R and S rats were given 0 or 1 mg cadmium/1. in drinking water and fed either a low salt (0.4% NaCl) or a high salt (4% NaCl...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.7928261
更新日期:1979-02-01 00:00:00
abstract:BACKGROUND:Modern toxicology is shifting from an observational to a mechanistic science. As part of this shift, high-throughput toxicity assays are being developed using alternative, nonmammalian species to prioritize chemicals and develop prediction models of human toxicity. METHODS:The nematode Caenorhabditis elegan...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.1409645
更新日期:2016-05-01 00:00:00
abstract::Martineau et al. (2002) reported that St. Lawrence beluga (SLB) have high cancer rates. Unfortunately, errors in their interpretation of the data have led them to overstate the importance of cancer and its links to environmental sources. ...
journal_title:Environmental health perspectives
pub_type: 评论,信件
doi:10.1289/ehp.111-a77c
更新日期:2003-02-01 00:00:00
abstract::As a result of the Leadership Conference on Biomedical Research and the Environment, the Facilities Committee focused its work on the development of best environmental practices at biomedical research facilities at the university and independent research facility level as well as consideration of potential involvement...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.00108s6945
更新日期:2000-12-01 00:00:00
abstract:BACKGROUND:In a changing climate, increasing temperatures are anticipated to have profound health impacts. These impacts could be mitigated if individuals and communities adapt to changing exposures; however, little is known about the extent to which the population may be adapting. OBJECTIVE:We investigated the hypoth...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.1307392
更新日期:2014-08-01 00:00:00
abstract:BACKGROUND:Many pesticides in current use have recently been revealed as in vitro androgen receptor (AR) antagonists, but information about their combined effects is lacking. OBJECTIVE:We investigated the combined effects and the competitive AR antagonism of pesticide mixtures. METHODS:We used the MDA-kb2 assay to te...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.1205391
更新日期:2012-11-01 00:00:00
abstract::Humans are exposed to a large number of environmental chemicals: Some of these may be toxic, and many others have unknown or poorly characterized health effects. There is intense interest in determining the impact of exposure to environmental chemical mixtures on human health. As the study of mixtures continues to evo...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.1510569
更新日期:2016-01-01 00:00:00
abstract::Previously, we found that exposure of neonatal rats to chlorpyrifos (CPF) produced brain cell damage and loss, with resultant abnormalities of synaptic development. We used the same biomarkers to examine prenatal CPF treatment so as to define the critical period of vulnerability. One group of pregnant rats received CP...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.021101097
更新日期:2002-11-01 00:00:00
abstract::Impairment of any of the major components of the immune system (T-cells, B-cells phagocytes, complement) may result in clinical immunodeficiency. Immune defects can arise from intrinsic or heritable defects of lymphoid elements, failure of normal cellular differentiation, viral infection or other acquired causes. Clin...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.82439
更新日期:1982-02-01 00:00:00
abstract::Restriction-fragment-length polymorphism analysis was performed on several different types of human cancers, including carcinoma of the uterine cervix, neuroblastoma, hepatocellular carcinoma, pheochromocytoma, stomach cancer, and small-cell lung carcinoma (SCLC), to determine the chromosomal loci of putative tumor-su...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.9193121
更新日期:1991-06-01 00:00:00
abstract::The instrumentation and practical circuitry required for the detection of negative ions exiting the mass analysis section of a mass spectrometer is examined. The potentials needed to bias the electron multiplier when detecting negative ions from a low ion-energy mass spectrometer, e.g., a quadrupole, are contrasted wi...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.803697
更新日期:1980-06-01 00:00:00
abstract::Toxicity testing in AS52 cells (24-hr exposures) gave LC50 values of 2 to 130 micrograms Ni/ml for particulate nickel compounds and 45 to 60 micrograms Ni/ml for water-soluble salts (NiCl2, NiSO4, Ni(CH3COO)2). The Ni(OH)2, NiCO3, and sulfides (Ni3S2, Ni7S6, "amorphous NiS") exhibited similar toxicities (LC50's of 2 t...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.94102s369
更新日期:1994-09-01 00:00:00
abstract:BACKGROUND:Environmental heat exposure is a public health concern. The impacts of environmental heat on mortality and morbidity at the population scale are well documented, but little is known about specific exposures that individuals experience. OBJECTIVES:The first objective of this work was to catalyze discussion o...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/EHP556
更新日期:2017-08-01 00:00:00
abstract::It has been hypothesized that environmental exposure to synthetic estrogenic chemicals and related endocrine-active compounds may be responsible for a global decrease in sperm counts, decreased male reproductive capacity, and breast cancer in women. Results of recent studies show that there are large demographic varia...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.00108487
更新日期:2000-06-01 00:00:00
abstract:BACKGROUND:Environmental air pollutants are inhaled as complex mixtures, but the long dominant focus of monitoring and research on individual pollutants has provided modest insight into pollutant interactions that may be important to health. Trends toward managing multiple pollutants to maximize aggregate health gains ...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.11654
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:Cadmium is a commonly occurring toxic food contaminant, but health consequences of early-life exposure are poorly understood. OBJECTIVES:We evaluated the associations between cadmium exposure and neurobehavioral development in preschool children. METHODS:In our population-based mother-child cohort study in...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.1104431
更新日期:2012-10-01 00:00:00
abstract::Studies have shown that female mosquitofish living downstream of a paper mill located on the Fenholloway River, Florida, have masculinized secondary sex characteristics, including altered anal fin development and reproductive behavior. Masculinization can be caused by exposure to androgens in the water or from an alte...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.02110s3429
更新日期:2002-06-01 00:00:00
abstract::Ambient monitoring of acid aerosols in four U.S. cities and in a rural region of southern Ontario clearly show distinct periods of strong acidity. Measurements made in Kingston, TN, and Steubenville, OH, resulted in 24-hr H+ ion concentrations exceeding 100 nmole/m3 more than 10 times during summer months. Periods of ...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.897943
更新日期:1989-02-01 00:00:00
abstract::The types of reactive intermediates generated upon reduction of chromium(VI) by glutathione or hydrogen peroxide and the resulting DNA damage have been determined. In vitro, reaction of chromium(VI) with glutathione led to formation of two chromium(V) complexes and the glutathione thiyl radical. When chromium(VI) was ...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.919253
更新日期:1991-05-01 00:00:00
abstract::Whole blood oxygen equilibrium curves (O2 ECs), blood buffer lines, and several hematologic properties were determined for adult guinea pigs exposed to 700 ppm methyl isocyanate (MIC) for 15 min. MIC inhalation effected a significant reduction of blood O2 affinity; the half-saturation pressure (P50) at 38 degrees C in...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.877235
更新日期:1987-06-01 00:00:00
abstract::In this study we investigated the potential impact of climate change in Portugal on heat-related mortality, air pollution-related health effects, and selected vectorborne diseases. The assessment used climate scenarios from two regional climate models for a range of future time periods. The annual heat-related death r...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.8431
更新日期:2006-12-01 00:00:00
abstract::Relative advantages and disadvantages and important design criteria for various exposure methods are presented. Five types of exposures are discussed: whole-body chambers, head-only exposures, nose or mouth-only methods, lung-only exposures, and partial-lung exposures. Design considerations covered include: air cleani...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.761617
更新日期:1976-08-01 00:00:00
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
更新日期:2000-08-01 00:00:00
abstract::In this paper we report DNA binding of butadiene monoepoxide, a first metabolite of 1,3-butadiene catalyzed by monooxygenases. We prepared alkylated purines as marker compounds for 32-P-postlabeling and electrochemical analysis and developed methods to measure the corresponding products. The traditional postlabeling a...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.96104s3655
更新日期:1996-05-01 00:00:00
abstract::Recent data from deep uranium mines in Czechoslovakia indicated that mines are exposed to other mutagenic factors in addition to radon daughter products. Mycotoxins were identified as a possible source of mutagens in these mines. Mycotoxins were examined in 38 samples from mines and in throat swabs taken from 116 mine...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.101-1521117
更新日期:1993-10-01 00:00:00
abstract::Dysmenorrhea is a common gynecologic disorder in women of reproductive age. Previous studies have found an association between current cigarette smoking and prevalence of dysmenorrhea. This study investigated the association between exposure to environmental tobacco smoke (ETS) and the occurrence of dysmenorrhea among...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.001081019
更新日期:2000-11-01 00:00:00
abstract::Airway mucus is a complex airway secretion whose primary function as part of the mucociliary transport mechanism is to to serve as renewable and transportable barrier against inhaled particulates and toxic agents. The rheologic properties necessary for this function are imparted by glycoproteins, or mucins. Some respi...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.9410289
更新日期:1994-06-01 00:00:00