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DCM (Dichloromethane) (Final, 2011)

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  • 1.
    Book/Book Chapter
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    The Merck index: An encyclopedia of chemicals, drugs, and biologicals
    (2001)
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  • 2.
    Book/Book Chapter
    Book/Book
    Chapter
    Dichloromethane
    ACGIH (2001) In Documentation of the threshold limit values and biological exposure indices (pp. D1). Cincinnati, OH: American Conference of Governmental Industrial Hygienists.
    Minus Sign. Click to see only selected choices. A TLV-TWA of 50 ppm (174 mg/m3) is recommended for occupational exposure to dichloromethane is part . . . Plus Sign. Click to expand choices. A TLV-TWA of 50 ppm (174 mg/m3) is recommended for occupational exposure to dichloromethane is part by analogy to the TLVs for trichloroethylene and the more potent CNS depressant, tetrachloroethylene. This value is intended to minimize the potential for elevation of carboxyhemoglobin and central nervous system (CNS) depression. Dichloromethane is considered a weak animal carcinogen based on liver and lung cancer in mice and benign mammary gland tumors in rats after chronic inhalation at high concentrations ( > = 1000 ppm). Accordingly, an A3, Confirmed Animal Carcinogen with Unknown Relevance to Humans, is assigned. Sufficient data were not available to recommend Skin or SEN notations or a TLV-STEL. Dichloromethane is a substance for which Biological Exposure Indices (BEIs) have been recommended (see BEI Documentation for Dichloromethane)
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  • 3.
    The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
    Peer
    Reviewed
    Journal
    Article
    Learning impairment in mice following acute exposure to dichloromethane and carbon tetrachloride
    Alexeeff, GV; Kilgore, WW (1983) Journal of Toxicology and Environmental Health 11:569-581.
    Minus Sign. Click to see only selected choices. Mice were exposed via inhalation to high concentrations of either dichloromethane (168 mg/l) or carbon . . . Plus Sign. Click to expand choices. Mice were exposed via inhalation to high concentrations of either dichloromethane (168 mg/l) or carbon tetrachloride (134.3 mg/l). The mice were tested for learning ability using a passive-avoidance conditioning task. Exposed animals were found to have a significantly decreased ability to learn when compared with controls. The 3-wk-old mice were more affected than the 5-wk-old and the 8-wk-old mice. The exposed animals were indistinguishable from controls in terms of motor activity, weight gain, and absence of analgesia.
  • 4.
    The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
    Peer
    Reviewed
    Journal
    Article
    Cytogenetic analyses of mice exposed to dichloromethane
    Allen, J; Kligerman, A; Campbell, J; Westbrook-Collins, B; Erexson, G; Kari, F; Zeiger, E (1990) Environmental and Molecular Mutagenesis 15:221-228.
    Minus Sign. Click to see only selected choices. Chromosome damage was studied in female B6C3F1 mice exposed to dichloromethane (DCM) by subcutaneous . . . Plus Sign. Click to expand choices. Chromosome damage was studied in female B6C3F1 mice exposed to dichloromethane (DCM) by subcutaneous or inhalation treatments. No increase in the frequency of either sister chromatid exchanges (SCEs) or chromosome aberrations (CAs) in bone marrow cells was observed after a single subcutaneous injection of 2,500 or 5,000 mg/kg DCM. Inhalation exposure to DCM for 10 days at concentrations of 4,000 or 8,000 ppm resulted in significant increases in frequencies of SCEs in lung cells and peripheral blood lymphocytes, CAs in lung and bone marrow cells, and micronuclei (MN) in peripheral blood erythrocytes. Lung cell CAs and blood erythrocyte MN reached frequencies of approximately two times control levels. Following a 3-month inhalation exposure to 2,000 ppm DCM, mice showed small but significant increases in lung cell SCEs and peripheral blood erythrocyte MN. These findings suggest that genotoxicity may play a role in the carcinogenicity of DCM in the lungs of B6C3F1 female mice.
  • 5.
    The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
    Peer
    Reviewed
    Journal
    Article
    Physiologically based pharmacokinetic modeling with dichloromethane, its metabolite, carbon monoxide, and blood carboxyhemoglobin in rats and humans
    Andersen, ME; Clewell, HJ, III; Gargas, ML; MacNaughton, MG; Reitz, RH; Nolan, RJ; McKenna, MJ (1991) Toxicology and Applied Pharmacology 108:14-27.
    Minus Sign. Click to see only selected choices. Dichloromethane (methylene chloride, DCM) and other dihalomethanes are metabolized to carbon monoxide . . . Plus Sign. Click to expand choices. Dichloromethane (methylene chloride, DCM) and other dihalomethanes are metabolized to carbon monoxide (CO) which reversibly binds hemoglobin and is eliminated by exhalation. We have developed a physiologically based pharmacokinetic (PB-PK) model which describes the kinetics of CO, carboxyhemoglobin (HbCO), and parent dihalomethane, and have applied this model to examine the inhalation kinetics of CO and of DCM in rats and humans. The portion of the model describing CO and HbCO kinetics was adapted from the Coburn-Forster-Kane equation, after modification to include production of CO by DCM oxidation. DCM kinetics and metabolism were described by a generic PB-PK model for volatile chemicals (RAMSEY AND ANDERSEN, Toxicol. Appl. Pharmacol. 73, 159-175, 1984). Physiological and biochemical constants for CO were first estimated by exposing rats to 200 ppm CO for 2 hr and examining the time course of HbCO after cessation of CO exposure. These CO inhalation studies provided estimates of CO diffusing capacity under free breathing and for the Haldane coefficient, the relative equilibrium distribution ratio for hemoglobin between CO and O2. The CO model was then coupled to a PB-PK model for DCM to predict HbCO time course behavior during and after DCM exposures in rats. By coupling the models it was possible to estimate the yield of CO from oxidation of DCM. In rats only about 0.7 mol of CO are produced from 1 mol of DCM during oxidation. The combined model adequately represented HbCO and DCM behavior following 4-hr exposures to 200 or 1000 ppm DCM, and HbCO behavior following 1/2-hr exposure to 5160 ppm DCM or 5000 ppm bromochloromethane. The rat PB-PK model was scaled to predict DCM, HbCO, and CO kinetics in humans exposed either to DCM or to CO. Three human data sets from the literature were examined: (1) inhalation of CO at 50, 100, 250, and 500 ppm; (2) seven 1/2-hr inhalation exposures to 50, 100, 250, and 500 ppm DCM; and (3) 2-hr inhalation exposures to 986 ppm DCM. An additional data set from human volunteers exposed to 100 or 350 ppm DCM for 6 hr is reported here for the first time. Endogenous CO production rates and the initial amount of CO in the blood compartment were varied in each study as necessary to give the baseline HbCO value, which varied from less than 0.5% to greater than 2% HbCO. The combined PB-PK model gave a good representation of the observed behavior in all four human studies.(ABSTRACT TRUNCATED AT 400 WORDS)
  • 6.
    The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
    Peer
    Reviewed
    Journal
    Article
    Physiologically based pharmacokinetics and the risk assessment process for methylene chloride
    Andersen, ME; Clewell, HJ III; Gargas, ML; Smith, FA; Reitz, RH (1987) Toxicology and Applied Pharmacology 87:185-205.
    Minus Sign. Click to see only selected choices. Methylene chloride (dichloromethane, DCM) is metabolized by two pathways: one dependent on oxidation . . . Plus Sign. Click to expand choices. Methylene chloride (dichloromethane, DCM) is metabolized by two pathways: one dependent on oxidation by mixed function oxidases (MFO) and the other dependent on glutathione S-transferases (GST). A physiologically based pharmacokinetic (PB-PK) model based on knowledge of these pathways was used to describe the metabolism of DCM in four mammalian species (mouse, rat, hamster, and humans). Kinetic constants for the model were derived from in vivo experiments or the literature. The model was constructed to distinguish contributions from the two pathways of metabolism in lung and liver tissue, and to permit extrapolation from rodents to humans. Model validation was conducted by comparing predicted blood concentration time-course data in rats, mice, and humans with experimental data from these species. The tumor incidence in two chronic studies of DCM toxicity in mice was correlated with various measures of target tissue dose calculated with the PB-PK model. Tumor incidence correlated well with tissue AUC (area under the concentration/time curve) and amount of DCM metabolized by the GST pathway. However, tumor incidence did not correlate with the amount of DCM metabolized by the MFO pathway. Because of its low chemical reactivity, DCM is unlikely to be directly involved in carcinogenesis. Consequently, metabolism of DCM by GST appears to be important in carcinogenesis. The PB-PK model was used to estimate target doses of presumed toxic chemical species in humans exposed to DCM by inhalation or by drinking water. Target tissue doses in humans exposed to low concentrations of DCM are 140- to 170-fold lower (inhalation) or 50- to 210-fold lower (drinking water) than would be expected from the linear extrapolation and body surface area factors which have been used in conventional risk assessment methods (D. V. Singh, H. L. Spitzer, and P. D. White (1985). Addendum to the Health Assessment Document for Dichloromethane (Methylene Chloride). EPA/600/8-82/004F). The PB-BK analysis thus suggests that conventional risk analyses greatly overestimate the risk in humans exposed to low concentrations of DCM. PB-PK considerations provide a scientific basis for risk assessment, improve experimental design in chronic studies, and structure collection of quantitative metabolic constants required for risk assessment.
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  • 7.
    The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
    Peer
    Reviewed
    Journal
    Article
    Transplacental passage of dichloromethane and carbon monoxide
    Anders, MW; Sunram, JM (1982) Toxicology Letters 12:231-234.
    Minus Sign. Click to see only selected choices. Maternal blood dichloromethane concentrations were higher than fetal blood dichloromethane concentrations . . . Plus Sign. Click to expand choices. Maternal blood dichloromethane concentrations were higher than fetal blood dichloromethane concentrations and maternal and fetal blood carbon monoxide concentrations were the same in pregnant rats exposed to 500 ppm of dichloromethane. Fetal blood carbon monoxide concentrations were higher than maternal blood carbon monoxide concentrations in pregnant rats exposed to 20 ppm of carbon monoxide. These results show that maternal exposure to dichloromethane is accompanied by fetal exposure to both dichloromethane and carbon monoxide.
    Tag:
  • 8.
    The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
    Peer
    Reviewed
    Journal
    Article
    Dichloromethane is not genotoxic in isolated rat hepatocytes
    Andrae, U; Wolff, T (1983) Archives of Toxicology 52:287-290.
  • 9.
    The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
    Peer
    Reviewed
    Journal
    Article
    The pharmacokinetics of dichloromethane. I. Disposition in B6C3F1 mice following intravenous and oral administration
    Angelo, MJ; Pritchard, AB; Hawkins, DR; Waller, AR; Roberts, A (1986) Food and Chemical Toxicology 24:965-974.
    Minus Sign. Click to see only selected choices. The tissue distribution and metabolism of dichloromethane (DCM; CH2Cl2) was investigated in B6C3F1 mice . . . Plus Sign. Click to expand choices. The tissue distribution and metabolism of dichloromethane (DCM; CH2Cl2) was investigated in B6C3F1 mice following iv or oral administration. The route of exposure and the composition of the dosing solution were found to have a significant effect on the pharmacokinetics. Following single iv doses of 10 or 50 mg [14C]DCM/kg dose-dependent metabolism to 14CO2 and 14CO and rapid pulmonary clearance of unchanged 14CH2Cl2 characterized the elimination of DCM from the body. The highest concentrations of 14CH2Cl2 were found in the liver, lung and kidney, with more than 50% of the total radioactivity in these tissues represented by the parent compound. When DCM was administered orally in single gavage doses for 14 consecutive days at treatment levels of 50 mg/kg in water or 500 and 1000 mg/kg in corn oil, rapid absorption and elimination of DCM characterized the treatment in water while distinctly slower trends were found for the doses in corn oil. No observable pharmacokinetic or metabolic effect resulted from repeated oral dosing over the 2-wk treatment period.
  • 10.
    The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
    Peer
    Reviewed
    Journal
    Article
    The pharmacokinetics of dichloromethane. II. Disposition in Fischer 344 rats following intravenous and oral administration
    Angelo, MJ; Pritchard, AB; Hawkins, DR; Waller, AR; Roberts, A (1986) Food and Chemical Toxicology 24:975-980.
    Minus Sign. Click to see only selected choices. The tissue distribution and metabolism of dichloromethane (DCM; CH2Cl2) was investigated in Fischer . . . Plus Sign. Click to expand choices. The tissue distribution and metabolism of dichloromethane (DCM; CH2Cl2) was investigated in Fischer 344 rats following iv or oral administration. The route and level of exposure were found to have a significant effect on the disposition characteristics. A two-compartment model was used to describe the elimination of DCM from blood following single iv doses. The estimates of t1/2,beta were 11.9 and 23.5 min for doses of 10 and 50 mg/kg, respectively, and the disposition rate constants, beta were found to differ significantly at P less than 0.05. When DCM was administered orally (by gavage) in a daily dose of 50 or 200 mg/kg for 14 consecutive days, rapid absorption and distribution to the tissues characterized the disposition. Dose-dependent metabolism to 14CO2 and 14CO and rapid pulmonary clearance of unchanged 14CH2Cl2 were the dominant routes of elimination of DCM from the body following both iv and oral doses. No observable pharmacokinetic or metabolic effect resulted from repeated oral dosing.
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