Abstract:
:During a 2-year chronic inhalation study on methylene chloride (2000 or 0 ppm; 6 hr/day, 5 days/week), gas-uptake pharmacokinetic studies and tissue partition coefficient determinations were conducted on female B6C3F1, mice after 1 day, 1 month, 1 year, and 2 years of exposure. Using physiologically based pharmacokinetic (PBPK) modeling coupled with Monte Carlo simulation and bootstrap resampling for data analyses, a significant induction in the mixed function oxidase (MFO) rate constant (Vmaxc) was observed at the 1-day and 1-month exposure points when compared to concurrent control mice while decreases in glutathione S-transferase (GST) rate constant (Kfc) were observed in the 1-day and 1-month exposed mice. Within exposure groups, the apparent Vmaxc maintained significant increases in the 1-month and 2-year control groups. Although the same initial increase exists in the exposed group, the 2-year Vmaxc is significantly smaller than the 1-month group (p < 0.001). Within group differences in median Kfc values show a significant decrease in both 1-month and 2-year groups among control and exposed mice (p < 0.001). Although no changes in methylene chloride solubility as a result of prior exposure were observed in blood, muscle, liver, or lung, a marginal decrease in the fat:air partition coefficient was found in the exposed mice at p = 0.053. Age related solubility differences were found in muscle:air, liver:air, lung:air, and fat:air partition coefficients at p < 0.001, while the solubility of methylene chloride in blood was not affected by age (p = 0.461). As a result of this study, we conclude that age and prior exposure to methylene chloride can produce notable changes in disposition and metabolism and may represent important factors in the interpretation for toxicologic data and its application to risk assessment.
journal_name
Environ Health Perspectjournal_title
Environmental health perspectivesauthors
Thomas RS,Yang RS,Morgan DG,Moorman MP,Kermani HR,Sloane RA,O'Connor RW,Adkins B Jr,Gargas ML,Andersen MEdoi
10.1289/ehp.96104858subject
Has Abstractpub_date
1996-08-01 00:00:00pages
858-65issue
8eissn
0091-6765issn
1552-9924journal_volume
104pub_type
杂志文章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::Repeated inhalation of silica dust can lead to inflammation and fibrosis in human lung and in experimental animal models. The alveolar macrophage is believed to play a pivotal role in this process. Numerous macrophage-derived growth factors, cytokines, and arachidonic acid metabolites have been shown to contribute to ...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.929777
更新日期:1992-07-01 00:00:00
abstract::It is generally agreed that estrogens, and possibly androgens, are important in the etiology of breast cancer, but no consensus exists as to the precise estrogenic or androgenic environment that characterizes risk, or the exogenous factors that influence the hormonal milieu. Nearly all the epidemiological studies cond...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.97105s3587
更新日期:1997-04-01 00:00:00
abstract::This paper summarizes the themes and recommendations that emerge from the papers presented by the Working Group on Tropospheric Ozone. In terms of current knowledge, the following are considered of particular importance: a) lack of clear evidence for a human analogue of the terminal bronchiolar and proximal acinar cha...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.93101s4237
更新日期:1993-12-01 00:00:00
abstract::In the aquatic environment, diet is an important route of exposure for the common contaminant and procarcinogen benzo(a)pyrene (BaP). Dietary organisms vary in their BaP content and in contaminated areas often contain other xenobiotics including cytochrome P4501A inducers. This study examined the effect of dose and pr...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.98106155
更新日期:1998-03-01 00:00:00
abstract::The metabolism of polybrominated biphenyls (PBBs) was studied in vitro by using rat liver microsomes in the presence of NADPH and atmospheric O2. Quantitative recoveries of all PBBs were obtained after incubations with control or 3-methylcholanthrene (MC) induced microsomes. Of the twelve major components, losses of o...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.782351
更新日期:1978-04-01 00:00:00
abstract::Fish and shellfish caught in polluted waters contain potentially dangerous amounts of toxic and carcinogenic chemicals. Public concern was heightened when a large percentage of winter flounder taken from Boston Harbor was found to have visible cancer of the liver; winter flounder outside the estuary area had no liver ...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.90-1519487
更新日期:1991-01-01 00:00:00
abstract::To examine the effects of dibutyl phthalate (DBP) on gonadal sex differentiation, genetically male tadpoles of Rana rugosa were exposed to dilute solutions of DBP at concentrations of 0.1, 1, or 10 microM during days 19-23 after fertilization, which is the critical period of gonadal sex differentiation in R. rugosa. T...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.001081189
更新日期:2000-12-01 00:00:00
abstract:BACKGROUND:Few studies have examined the relationship between long-term exposure to ambient fine particulate matter (PM2.5) and nonaccidental mortality in rural populations. OBJECTIVE:We examined the relationship between PM2.5 and nonaccidental and cardiovascular mortality in the U.S. Agricultural Health Study cohort....
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.1307277
更新日期:2014-06-01 00:00:00
abstract::Until recently, mutagenicity testing was done on preselected compounds in a manner in which the testing laboratories knew the identity of the substances under test and the "expected" results, i.e., positive for compounds selected because of their carcinogenicity and negative for food additives. There is no completed s...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.7720253
更新日期:1977-10-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to assess whether the joint effects of three androgen receptor antagonists (vinclozolin, flutamide, procymidone) on male sexual differentiation after in utero and postnatal exposures can be predicted based on dose-response data of the individual chemicals. METHODS:Test chemicals and...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.9360
更新日期:2007-12-01 00:00:00
abstract::In the National Toxicology Program 2-year inhalation study of dichloromethane (DCM), there was a significant increase in pulmonary neoplasms in female B6C3F1 mice exposed to 2000 ppm (overall rates of 30/48 versus 5/50 in control). Replicative DNA synthesis was examined to evaluate the potential role of treatment-indu...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.93101s5271
更新日期:1993-12-01 00:00:00
abstract::Organophosphate (OP) pesticides are commonly used in the United States, and farmworkers are at risk for chronic exposure. Using a sample of 218 farmworkers in 24 communities and labor camps in eastern Washington State, we examined the association between agricultural crop and OP pesticide metabolite concentrations in ...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.8620
更新日期:2006-07-01 00:00:00
abstract::Previously, we showed that diesel exhaust particles (DEPs) suppressed pulmonary clearance of Listeria monocytogenes (Listeria) and inhibited the phagocytosis of alveolar macrophages and their response to Listeria in the secretion of interleukin (IL)-1 beta, tumor necrosis factor alpha, and IL-12. In this report we exa...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.5709
更新日期:2003-04-01 00:00:00
abstract::This report reviews the recent literature on the adverse effects of occupational factors on fertility and related reproductive outcomes. Few studies fulfill the criteria of good study design because of small sample size, insensitive measures of effect, selection, recall, and observation bias, weak if any control of co...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.93101s281
更新日期:1993-07-01 00:00:00
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
更新日期:2003-05-01 00:00:00
abstract:BACKGROUND:Microcystin-LR, a cyclic heptapeptide, possesses the ability to inhibit the serine/threonine protein phosphatases PP1 and PP2A and, consequently, exhibits acute hepatocytotoxicity. Moreover, microcystin-LR induces cellular proliferation, resulting in tumor-promoting activity in hepatocytes. However, mechanis...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.1001899
更新日期:2010-09-01 00:00:00
abstract::Human health and aquatic animal health are organically related at three distinct interfaces. Aquatic animals serve as important contributors to the nutritional protein, lipid, and vitamin requirements of humans; as carriers and transmitters of many infectious and parasitic diseases to which humans are susceptible; and...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.9086245
更新日期:1990-06-01 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::Molecular epidemiology has significant potential in preventing cancer and other diseases caused by environmental exposures (related to lifestyle, occupation, or ambient pollution). This approach attempts to prevent cancer by incorporating laboratory methods to document the molecular dose and preclinical effects of car...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.96104s3441
更新日期:1996-05-01 00:00:00
abstract::Human exposure to carcinogenic Cr(VI) compounds is found among workers in a large number of professional groups, and it can also occur through environmental pollution. A significant number of toxic waste sites contain Cr as a major contaminant. In this paper we summarize our efforts to apply measurements of DNA-protei...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.98106s4969
更新日期:1998-08-01 00:00:00
abstract::In this paper we give some examples of using databases of genotoxicity and carcinogenicity for quantitative and qualitative correlation studies between short-term tests and carcinogenicity. The quality of the databases is obviously important, but one of the major deficiencies of present databases is that they are too ...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.919661
更新日期:1991-12-01 00:00:00
abstract::Many substances are active in in vitro tests for estrogenic activity, but data from multigenerational and other toxicity studies are not available for many of those substances. Controversy has arisen, therefore, concerning the likelihood of adverse health effects. Based on a toxic equivalence factor risk assessment ap...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.97105s3655
更新日期:1997-04-01 00:00:00
abstract::In this study, we explored the efficacy of upper-room ultraviolet germicidal irradiation (UVGI) in reducing the concentration of Serratia marcescens and Mycobacterium bovis bacille Calmette-Guérin (BCG) aerosols in enclosed places. We constructed a facility (4.5 m x 3 m x 2.9 m) in which both ceiling- and wall-mounted...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.0211095
更新日期:2002-01-01 00:00:00
abstract::The spatial and temporal regulation of intracellular free Ca2+ serves as a modulator of signal transduction pathways involved in cell growth and differentiation. Thus, interference of metals with intracellular Ca2+ homeostasis has been considered as a target of toxic action. We used the fluorescence indicator fura-2 t...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.94102s3265
更新日期:1994-09-01 00:00:00
abstract::Between 1966 and 1986, the childhood leukemia rate in Woburn, Massachusetts, was 4-fold higher than the national average. A multidisciplinary research team from MIT, which is being supported by the NIEHS Superfund Basic Research Program, has explored the possible importance of a temporal correlation between the period...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.95103s693
更新日期:1995-09-01 00:00:00
abstract::This subject concerns the complex interrelationship of a genetically determined protein deficiency, enzymes which are inhibited by that protein, environmental challenges such as cigarette smoke and industrial pollutants, and the occurrence of obstructive lung disease (Fig. 1). Unequivocal establishment of an etiologic...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.792957
更新日期:1979-04-01 00:00:00
abstract::There is concern about the human health effects of inhalation of acid compounds found in urban air pollution. It was the purpose of this study to investigate three of these acid compounds, sulfur dioxide (SO2), sulfuric acid (H2SO4), and nitric acid (HNO3) in a group of allergic adolescent subjects. Subjects were expo...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.8979173
更新日期:1989-02-01 00:00:00
abstract::The many anatomical, physiological, and biochemical differences among various mammalian species make it difficult to extrapolate carcinogenic potency data from animals to humans. The process is further complicated by the multistep origin of most malignant tumors in animals and humans due to the interaction of target c...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.887773
更新日期:1988-04-01 00:00:00
abstract:BACKGROUND:Associations between airborne particles and health outcomes have been documented worldwide; however, there is limited information regarding health effects associated with different particle sizes. OBJECTIVES:We explored the association between size-fractionated particle number concentrations (PNCs) and dail...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.1206398
更新日期:2013-10-01 00:00:00