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Results for “METHYLENE CHLORIDE”

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PubMed1975

Exposure to methylene chloride. II. Psychological functions.

The effect of the solvent methylene chloride on psychological functions such as reaction time, short-term memory, and numerical ability was studied in 14 healthy male subjects. Each subject was tested repeatedly during exposure to 870, 1,740, 2,600, and 3,470 mg/m3 of methylene choride in inspiratory air and during control conditions. Samples of sub ject alveolar air were taken every third minute during the experiments. No statistically significant impairement in the performance of examined functions could be observed during exposure to methylene choride as compared to control conditions. Inexposure to the highest concentration a greater irregularity of response was obtained for subject reaction time than under control conditions.

Adult↗

PubMed1988

Long-term carcinogenicity bioassays on methylene chloride administered by ingestion to Sprague-Dawley rats and Swiss mice and by inhalation to Sprague-Dawley rats.

Methylene chloride was administered to Sprague-Dawley rats and Swiss mice by ingestion (stomach tube), in olive oil, at the doses of 500, 100 and 0 mg/kg body weight, once daily, 4-5 days weekly, for 64 weeks, and to Sprague-Dawley rats by inhalation, at the concentration of 100 and 0 ppm, 7 hours daily, for 5 days weekly. The inhalatory treatment was started on 13-week-old breeders, and male and female offspring (12-day embryos). The breeders and part of the offspring were exposed for 104 weeks; the other part of the offspring was exposed for 15 weeks only. The most important findings were: (1) the increased incidence of pulmonary tumors in male mice treated by ingestion at 500 mg/kg body weight; (2) a not-significant increase in total malignant tumors in rats exposed by inhalation at 100 ppm for 104 weeks; and (3) a not-significant increase in total malignant mammary tumors in female rats given methylene chloride by ingestion at 500 mg/kg body weight.

Administration, Inhalation↗

PubMed1980

Blood pressure reduced by methylene chloride. A study in spontaneously hypertensive rats.

Effects of methylene chloride (CH2Cl2) on blood pressure (BP), body weight, plasma renin activity, hepatic histological structure of spontaneously hypertensive rats (SHRs) and normotensive control rats (NCRs) were studied. Administration of 0.15 mL/100 g/day CH2Cl2 to SHRs for five days reduced the BP from 172 +/- 7 mm Hg (mean +/- SEM) to 155 +/- 6 mm Hg without changing the plasma renin activity. The same regimen did not change the BP of NCRs. A weekly injection of 0.15 mL/100 g/day of CH2Cl2 for five consecutive weeks failed to significantly alter the BP of either SHRs or NCRs. The polyhalogen, whether administered daily or weekly, did not affect the body weight of either SHRs or NCRs. Administration of CH2Cl2 daily for five days produced an extensive but reversible hepatic centrolobular loss of glycogen in both SHRs and NCRs. No other changes were observed in the livers.

Angiotensin I↗

PubMed1996

Mouse liver glutathione S-transferase mediated metabolism of methylene chloride to a mutagen in the CHO/HPRT assay.

Although methylene chloride (MC) is readily detectable as a bacterial mutagen, published studies in mammalian cells have been inconclusive. We have previously shown (Graves et al., 1995) that glutathione S-transferase (GST)-mediated metabolism of MC by mouse liver cytosol (S100 fraction) causes DNA single-strand (ss) breaks in CHO cells. In this study, MC GST metabolites were shown to cause mutations at the HPRT locus of CHO cells. The mutagenicity of MC was enhanced by exposing the cells in suspension rather than as attached cultures. The MC GST metabolite formaldehyde was mutagenic in independent experiments, although the number of mutants induced was lower than with the MC. CHO HPRT mutations were also induced by the reference genotoxin 1,2-dibromoethane (1,2-DBE), which is activated to a mutagen by GST-mediated metabolism. Assay of DNA ss breaks and DNA-protein cross-links at mutagenic concentrations of MC, formaldehyde or 1,2-DBE, showed that all three compounds induced DNA ss breaks, but only formaldehyde induced significant DNA-protein cross-linking. These results suggest that whilst formaldehyde may play a role in MC mutagenesis, its weak mutagenicity and the absence of significant DNA-protein cross-linking after MC exposure, leads to the conclusion that the MC DNA damage and resulting mutations are induced by the glutathione conjugate of MC, S-chloromethylglutathione.

Animals↗

PubMed2001

Effects of the aqueous and methylene chloride extracts of Bidens pilosa leaf on fructose-hypertensive rats.

We investigated the effects of the aqueous (150-350 mg/kg) and methylene chloride (150-300 mg/kg) extracts of Bidens pilosa on fructose-induced hypertension in rats. Food and liquid intake were measured as well as systolic blood pressure and plasma levels of glucose, insulin, cholesterol, triglycerides and creatinine. Fructose feeding for 6 weeks induced hypertension, hyperinsulinemia and increased plasma triglyceride levels in male Wistar rats. The aqueous and methylene chloride extracts of B. pilosa reversed the high blood pressure and hypertriglyceridemia developed due to fructose feeding but did not have any effects on plasma levels of insulin and glucose. High doses of the extracts reduced plasma creatinine levels and tended to increase plasma cholesterol. These results suggest that the extracts of B. pilosa possess hypotensive effects whose mechanism of action is not related to insulin sensitivity.

Animals↗

PubMedDate not supplied

A comparative study of the effects of carbon monoxide and methylene chloride on human performance.

The purpose of this investigation was to determine whether similar carboxyhemoglobin (COHb) values obtained from inhaling carbon monoxide or methylene chloride have the same behavioral effects. The effects were assessed by the performance of 12 humans on a visual-manual, dual-task, and an auditory vigilance task. The results indicated that both substances in concentrations sufficient to produce 5-percent COHb significantly impaired human performance under difficult or demanding task conditions. The conclusion was that carbon monoxide, the main metabolite of methylene chloride, was responsible for the observed performance decrements.

Adolescent↗

PubMed1983

Comparative renal and hepatotoxicity of halomethanes: bromodichloromethane, bromoform, chloroform, dibromochloromethane and methylene chloride.

The renal and hepatotoxicities of five selected halomethanes, which are drinking water contaminants, were evaluated following a 14-day exposure. Bromodichloromethane, bromoform, chloroform, dibromochloromethane and methylene chloride were administered at three dose levels. Toxicity was evaluated by measuring changes in total body weight, uptake of p-aminohippurate into renal cortical slices, blood urea nitrogen, serum creatinine, and serum glutamate-pyruvate transaminase levels and by performing a histopathologic examination of liver and kidney tissues. Dose-related effects on the liver and kidney were detected with the uptake of p-aminohippurate into kidney slices and with the histopathologic evaluation of tissues. Treatment-related effects seen in the methylene chloride exposed mice were less pronounced as compared to the other halomethane treatment groups. In general, histopathological changes were the most sensitive indicators of both liver and kidney damage.

Animals↗

PubMed1991

Neurotoxic effects of methylene chloride: are they long lasting in humans?

The neurotoxicity of methylene chloride (MC) is of special interest because of its acute effects on the central nervous system (CNS) and its metabolic conversion to carbon monoxide. A cohort study of retired airline mechanics was conducted to examine the hypothesis that long term exposure to MC results in lasting effects on the CNS. Retirees were studied to eliminate effects of current occupational exposures. The total retiree population (n = 1758) was surveyed to identify mechanics who met specific occupational, demographic, and medical criteria. A group of eligible retirees having long term exposure to MC and another group with low probability of exposure to solvents were given a comprehensive battery of physiological and psychological tests. The exposure groups were similar for all potential confounders that were measured. No statistically significant differences between groups were detected on outcome measures, although subtle differences in attention and memory were identified. Thus no firm evidence was found to support the hypothesis of lasting CNS effects in retired mechanics with long term exposure to MC.

Aged↗

PubMed1979

Whole-body autoradiography and allied tracer techniques in distribution and elimination studies of some organic solvents: benzene, toluene, xylene, styrene, methylene chloride, chloroform, carbon tetrachloride and trichloroethylene.

Whole-body autoradiography has been used to study the distribution and fate of 14C-labeled benzene, toluene, xylene, styrene, methylene chloride, chloroform, carbon tetrachloride and trichloroethylene in mice after inhalational exposure. Total radioactivity, including the volatile part of the solvents were registered by autoradiography of dried, evaporated tape-fastened sections. In addition, dried, evaporated tape-fastened sections were extracted with water, trichloroacetic acid and a series of organic solvents and autoradiographed to register organs where metabolites were firmly bound. In another facet of the study, the quantitative elimination of the solvents and their metabolites via various routes was investigated. The expiration of unchanged solvents was subject to mathematical and computerized compartmental pharmacokinetic analysis. All solvents were rapidly taken up in fatty and nervous tissues where they were retained for different periods of time largely dependent on their fat solubility. Unexpectedly long retention times were noted for the chlorinated solvents, particularly for chloroforn, which showed a specific long-term retention in the cerebellum, meninges and spinal nerves, indicating interactions with specific nervous tissue receptors. Solvent metabolites appeared rapidly in several organs, mainly the liver and kidney, and were excreted both via urine and bile. Toluene and xylene metabolites were completely extractable whereas firmly bound metabolites were registered after inhalation of benzene, styrene and all chlorinated solvents, notably in the liver and kidney but also in the bronchi of the lung. Three-compartment pharmacokinetics were observed for the majority of the solvents selected for study although a two-compartment model was found to fit the elimination rate curves for styrene, methylene chloride and chloroform in the exhaled air. The fat solubility of the solvents was found to influence their pharmacokinetics since lower rate constants were generally obtained for the expiration of more fat soluble solvents.

Adipose Tissue↗

PubMed1999

Mortality study of two overlapping cohorts of photographic film base manufacturing employees exposed to methylene chloride.

The mortality experience of two overlapping cohorts of employees engaged in the manufacture of photographic film support was evaluated to assess the potential chronic health effects of methylene chloride exposure. In the first analysis, we examined causes of death among 1311 men initially employed between 1946 (when the solvent was first used) and 1970; in the second, we updated mortality in a 1964 to 1970 employed cohort of 1013 men. Follow-up was through 1994. The mean exposure among members of the 1946 to 1970 cohort was 39 ppm (8-hour time-weighted average) for 17 years, and the median length of follow-up from first exposure was 34 years. Members of the 1964 to 1970 cohort received an average exposure of 26 ppm for 24 years; median time from first exposure was 35 years. Compared with general population vital statistics, mortality in both cohorts was below expectation for all causes of death, ischemic heart disease, and cancer, including such sites as the lung and liver, which were target organs identified in animal toxicology studies. No statistically significant increases were observed for any cause of death. The combined results of this study and three others in the photographic film and textile fibers industries (approximately 7300 subjects) show that long-term exposure to methylene chloride does not increase the risk of death from any cause including specific diagnoses that have been associated with this widely used solvent.

Adult↗

PubMed1995

Incorporating biological information in quantitative risk assessment: an example with methylene chloride.

The interplay between chemical risk assessment and scientific research is discussed in the context of recent attempts to improve the scientific basis for estimates of the human carcinogenic risk from methylene chloride. A combination of basic biochemical research and risk assessment oriented research, both mechanistic and pharmacokinetic, provided the initial impetus for re-evaluating the use of the default risk estimation approach. Resulting efforts to incorporate the new scientific information into the risk assessment process in turn identified specific additional research needed to reduce uncertainty in the estimated risk. This healthy interchange between the two disciplines has served both to refine the human risk estimates for methylene chloride and to more clearly identify key scientific issues for chemical risk assessment in general.

Animals↗

PubMed2000

Effects of methanol, cyclohexane and methylene chloride extracts of Bidens pilosa on various gastric ulcer models in rats.

Ethnobotanical studies have revealed that Bidens pilosa is used in the traditional management of wounds and chronic gastro-duodenal ulcers. This led us to screen the methanol, cyclohexane and methylene chloride extracts of the plant for anti-ulcerogenic activity using the HCl/ethanol gastric necrotizing solution. The methylene chloride extract, which showed the highest activity (100% inhibition) at a dose of 750 mg/kg compared with the methanol and cyclohexane extracts (41 and 46% inhibition, respectively), was further tested using the indomethacin-HCl/ethanol-, absolute ethanol- and pylorus ligation-induced ulcer methods. Pre-treatment with indomethacin significantly reduced the protective effect of the extract against HCl/ethanol solution to 31%. The extract had very little gastric mucosal protection against absolute ethanol (9.8% inhibition at 750 mg/kg) compared with the controls and neither reduced gastric acid secretion in vivo nor the acidity of gastric juice following in vitro incubation.

Animals↗

PubMed2006

Diffusive sampling of methylene chloride with solid phase microextraction.

This study examined the characteristics of a solid phase microextraction (SPME) assembly as a passive sampler to determine the short-term exposure level (STEL) of methylene chloride. Two types of SPME fibers and six sampling-related factors were chosen and nested in an L(18) Taguchi's orthogonal array. Samples were thermally desorpted and analyzed by gas chromatograph equipped with an electron capture detector (GC/ECD). The use of 85-mum Carboxen/polydimethylsiloxane (Car/PDMS) fibers resulted in greater adsorbed mass, which was highly correlated with the product of concentration and sampling time (r>0.99, p<0.0001), than 85-microm polyacrylate fibers. The sampling rate (SR) of the 85-microm Carboxen/polydimethylsiloxane fibers was not significantly affected by variations in relative humidity (0-80%) and coexistent toluene (none to 100 ppm). Variance of sampling rate was predominantly attributed to the diffusive path length (86.4%) and sampling time (5.7%). With diffusive paths of 3, 10 and 15 mm, the sampling rates of 85-microm Carboxen/polydimethylsiloxane fibers for methylene chloride were 1.4 x 10(-2), 7.7 x 10(-3) and 5.1 x1 0(-3)mL min(-1), respectively. The measured sampling rates were greater than the theoretical values, and decreased with increment of sampling time until they came to constant.

Chromatography, Gas↗

PubMed1975

Determination of methylene chloride, ethylene dichloride, and trichloroethylene as solvent residues in spice oleoresins, using vacuum distillation and electron capture gas chromatography.

A quantitative gas chromatographic (GC) method is described for the determination of residual methylene chloride, ethylene dichloride, and trichloroethylene in spice oleoresins. The proposed method involves vacuum distillation in a closed system with toluene as a carrier solvent. Quantitation by electron capture GC on Porapak Q is facilitated by water extraction and by the addition of trans-1,2-dichloroethylene as an internal standard. Recoveries from oleoresins spiked at 30, 15, and 6 ppm ranged from 93 to 102%. To assess the possibility of interference from spice volatiles, the procedure was applied to 17 different spice oleoresins from 3 different manufacturers. No interferences were found, but methylene chloride levels up to 83 ppm and ethylene dichloride levels up to 23 ppm were detected. Trichloroethylene was not detected in any of the oleoresins.

Chromatography, Gas↗

PubMed1976

Use of breath analysis to monitor methylene chloride exposure.

Twenty male and female subjects were exposed repetitively to methylene chloride (CH2Cl2) vapor, 50, 100, 250, and 500 ppm, for 1,3, or 7.5 h in a controlled-environment chamber. Postexposure alveolar breath samples were collected in small glass breath tubes and analyzed for CH2Cl2 by gas chromatography. From these data is a series of breath CH2Cl2 excretion curves were constructed that can be used to estimate the magnitude of a recent exposure. The CH2CL2 breath concentration in the immediate postexposure period accurately reflected the vapor concentration to which the subjects had been exposed most recently. Breath samples collected 1--2 h following exposure were accurate indicators of the time-weighted average vapor exposure experienced by the subjects during the previous 8 h of occupational exposure. Breath analysis offers a practical, noninvasive method for monitoring occupational exposure to CH2Cl2.

Adult↗

PubMed1994

Sensitivity of physiologically based pharmacokinetic models to variation in model parameters: methylene chloride.

The parameters in a physiologically based pharmacokinetic (PBPK) model of methylene chloride were varied systematically, and the resulting variation in a number of model outputs was determined as a function of time for mice and humans at several exposure concentrations. The importance of the various parameters in the model was highly dependent on the conditions (concentration, species) for which the simulation was performed and the model output (dose surrogate) being considered. Model structure also had a significant impact on the results. For sensitivity analysis, particular attention must be paid to conservation equations to ensure that the variational calculations do not alter mass balance, introducing extraneous effects into the model. All of the normalized sensitivity coefficients calculated in this study ranged between -1.12 and 1, and most were much less than 1 in absolute value, indicating that individual input errors are not greatly amplified in the outputs. In addition to ranking parameters in terms of their impact on model predictions, time-dependent sensitivity analysis can also be used as an aid in the design of experiments to estimate parameters by predicting the experimental conditions and sampling points which will maximize parameter identifiability.

Animals↗

PubMed1984

A physiological model for the pharmacokinetics of methylene chloride in B6C3F1 mice following i.v. administrations.

A physiologic mathematical model was developed to describe the time course of 14C-methylene chloride (14CH2Cl2) distribution and elimination in mice following single i.v. administrations of 10 and 50 mg/kg. A whole-body model was used to simulate 14CH2Cl2 concentrations in blood and tissues, pulmonary clearance of unchanged 14CH2Cl2, and metabolic conversion to 14CO2 and 14CO as monitored by the appearances of these metabolites in expired breath. This diffusion-limited model was identified via a sequential optimization scheme using hybrid models for each compartment. Pulmonary elimination of unchanged 14CH2Cl2 was modeled as a linear process while hepatic metabolism of 14CH2Cl2 to the compounds 14CO2 and 14CO was described by a saturable metabolic rate term. The model adequately described the dose dependence in methylene chloride distribution and metabolism when simulations were compared to experimental data.

Animals↗

PubMedDate not supplied

Chemical characterization of sanding dust and methylene chloride usage in automotive refinishing: implications for occupational and environmental health.

Surface preparation activities conducted during automotive refinishing present several potential human health and environmental risks. This study examines the chemical composition of vehicle sanding dust and the prevalence of methylene chloride use as a basis for evaluating potential chemical exposures in the work environment, fugitive environmental releases, and take-home toxics. This article reports on the findings of (1) a statewide technology and work practices survey of 353 licensed auto body shops and (2) laboratory analyses of sanding dust representing more than 200 vehicles, 10 commercial body filler compounds, and work shirts worn during vehicle sanding while using nonventilated equipment. Survey data revealed that the majority of shops (78%) do not use ventilated sanding equipment, that most workers (55%) take their work clothes and shoes home at the end of the workday, and that 17% of the respondents used a methylene chloride-based paint stripper as an adjunct to mechanical sanding. Laboratory results showed that Pb, As, Cr, Mn, and Ni were present in the sanding dust at every facility tested. Lead concentrations in sanding dust were found to be highest at facilities that performed complete vehicle refinishing (range 770 to 7300 ppm) and at a collision repair shop that used a high-lead content body filler compound (1800 ppm). Hexavalent chromium also was found in two vocational high school paint dust samples at concentrations of 54 and 710 ppm. When total lead and chromium concentrations reached 7300 and 2300 ppm, respectively, facility sanding dust samples failed the U.S. Environmental Protection Agency's Toxicity Characteristic Leaching Procedure for hazardous waste. Metals found in the sanding dust also were present on the work shirts of technicians-ranging from 0.06 (Cd) to 81 (Mg) microg/inch2 of cloth-who sanded on paint without ventilated equipment. Results suggest that sanding dust and methylene chloride paint strippers used in vehicle resurfacing operations pose a potential hazard to human health and the environment.

Automobiles↗