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At least 73 records · Page 4Linked to original sources
PubMed1986

Inhibition of methyl chloride toxicity in male F-344 rats by the anti-inflammatory agent BW755C.

This study examined the effectiveness of the cyclooxygenase/lipoxygenase inhibitor 3-amino-1-[m-(trifluoromethyl)phenyl]-2-pyrazoline (BW755C) in preventing the toxicity induced in male F-344 rats by methyl chloride (MeCl). BW755C (10 mg/kg ip, 1 hr pre and postexposure) prevented both lethality (0/6 vs 8/12 in controls) and epididymal granuloma formation (0/6 vs 4/4 in controls) in rats exposed to 7500 ppm MeCl 6 hr/day for 2 days. Additional rats (n = 5 per group) were exposed to 5000 ppm MeCl 6 hr/day for 5 days, with and without BW755C treatment as described above. The rats were killed on Day 5 and tissues processed for light microscopic examination. MeCl-exposed rats showed hepatocellular cloudy swelling, degeneration of renal proximal convoluted tubules, vacuolar degeneration in the adrenal cortex, necrosis of the internal granular layer of the cerebellum, and degenerative changes in the testis and epididymis, including formation of epididymal sperm granulomas. With the exception of the adrenal, tissues examined in rats of the MeCl/BW755C treatment group showed virtually no histologic evidence of lesions. BW755C did not significantly alter metabolism of [14C]MeCl to 14CO2 or 14C in urine, nor did it affect the distribution to various organs of radioactivity derived from [14C]MeCl. Therefore, BW755C protection against MeCl toxicity did not appear to result from altered MeCl metabolism or disposition. Instead, the protection was apparently related to the pharmacologic activity of BW755C as an inhibitor of leukotriene and prostaglandin synthesis.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1972

Inhibition of Sterol Biosynthesis by 2-Isopropyl-4-dimethylamino-5-methylphenyl-1-piperidine Carboxylate Methyl Chloride in Tobacco and Rat Liver Preparations.

2-Isopropyl-4-dimethylamino-5-methylphenyl-1-piperidine carboxylate methyl chloride, 90%, applied to rootless tobacco (Nicotiana tabacum cv. Samson) seedlings inhibits the incorporation of (14)C-mevalonate into sterols. Concomitantly, the retardant causes the accumulation of squalene-2,3-epoxide, an intermediate in sterol biosynthesis. The results with tobacco are identical to those produced by the retardant in cell-free rat liver preparations.

Journal Article↗
PubMed1986

Unscheduled DNA synthesis in rat tracheal epithelial cells, hepatocytes and spermatocytes following exposure to methyl chloride in vitro and in vivo.

Measurement of DNA repair as unscheduled DNA synthesis (UDS) in vitro following exposure in vivo in multiple tissues from the same treated animal can provide valuable information relating to the tissue- and organ-specificity of chemically induced DNA damage. UDS was evaluated in primary cultures of rat tracheal epithelial cells, hepatocytes and pachytene spermatocytes after exposure in vitro to methyl chloride (MeCl), and after isolation from the same treated animal following inhalation exposure in vivo. Concentrations of 1-10% MeCl in vitro induced UDS in hepatocytes and spermatocytes, but not in tracheal epithelial cells. Inhalation exposure to MeCl in vivo (3000-3500 ppm 6 h/day for 5 successive days) failed to induce DNA repair in any cell type. In vivo exposure to 15 000 ppm MeCl for 3 h also failed to induce UDS in tracheal epithelial cells and spermatocytes, but did cause a marginal increase in UDS in hepatocytes. Thus, MeCl appears to be a weak, direct-acting genotoxicant. While activity could be measured in hepatocytes and spermatocytes directly in vitro, only extremely high concentrations of MeCl elicited a response in the whole animal, and then only in hepatocytes.

Animals↗
PubMed1998

Methyl Chloride nu5 Region Lineshape Parameters and Rotational Constants for the nu2, nu5, and 2nu3 Vibrational Bands.

Fourier spectra of methyl chloride have been obtained at ambient laboratory temperature under self-broadening conditions. Five thousand two hundred and sixty rovibrational transitions of the (nu2, nu5, 2nu3)-vibrational-band triad have been assigned, and new ground and excited state rotational constants for CH335Cl and CH327Cl have been determined. The nu5 and nu2 vibrational-band intensities are determined to be, respectively, 42(1.2) and 31.7(0.9) cm-2 atm-1. Self-broadening coefficients of individual rovibrational lines are determined for the nu5 band of CH335Cl and CH337Cl at 296 K. The self-broadening coefficients peak broadly close to the maximum in the Boltzmann rotational population; no specific trends of the broadening coefficients are observed with the rotational quantum number K. With the exception of the RQ(J, 0) branch, the 1260-1650 cm-1 spectral region can be well modeled by the superposition of overlapping Voigt line profiles. To adequately model the densely packed RQ(J, 0) branch, however, we included collisional line mixing with A+ to A- in addition to A- to A- and A+ to A+ |DeltaJ| >/= 1, DeltaK = 0 collisional transitions allowed. Copyright 1998 Academic Press.

Journal Article↗
PubMed2005

Photodynamic therapy with PhotoPoint photosensitiser MV6401, indium chloride methyl pyropheophorbide, achieves selective closure of rat corneal neovascularisation and rabbit choriocapillaris.

AIM: The new photosensitiser PhotoPoint MV6401, indium chloride methyl pyropheophorbide, was assessed as a possible ocular photodynamic therapy agent in a rat model of experimentally induced corneal neovascularisation and in choriocapillaris closure in the rabbit. Optimal drug and light activation parameters were determined. METHODS: MV6401 (Miravant Pharmaceuticals, Inc, Santa Barbara, CA, USA) was activated at 664 nm using a DD3-0665 (Miravant Systems Inc) 0.5 W diode laser. Corneal neovascularisation in rats was induced using an N-heptanol technique. The evaluated drug dosages, light dosages, and post-injection activation times ranged from 0.01-0.1 micromol/kg, 5-25 J/cm(2), and 10-60 minutes, respectively. The efficacy of MV6401 on normal choriocapillaris and choroidal vessels was evaluated in rabbits with indirect ophthalmoscopy, fundus photography, fluorescein angiography, and histology. In rabbits, the evaluated drug dosages, light dosages, and post-injection activation times ranged from 0.025-0.25 micromol/kg, 3.3-20 J/cm(2), and 10 minutes, respectively. RESULTS: In the rat corneal neovascularisation model, an optimal intravenous drug dosage of 0.075 micromol/kg was activated by a 20 J/cm(2) light dose at 10 minutes after drug administration, the results of which demonstrated early evidence of efficacy in ocular neovascularisation. In rabbits, closure of the normal choriocapillaris was selectively achieved at a drug dosage of 0.15 micromol/kg using light doses from 3.3 to 20 J/cm(2). CONCLUSION: PhotoPoint MV6401 is a potent photosensitiser that demonstrates both efficacy and selectivity in experimental ocular models.

Animals↗
PubMed1998

Species differences in the glutathione transferase GSTT1-1 activity towards the model substrates methyl chloride and dichloromethane in liver and kidney.

Glutathione transferase (GST) GSTT1-1 is involved in the biotransformation of several chemicals widely used in industry, such as butadiene and dichloro methane DCM. The polymorphic hGSTT1-1 may well play a role in the development of kidney tumours after high and long-term occupational exposure against trichloroethylene. Although several studies have investigated the association of this polymorphism with malignant diseases little is known about its enzyme activity in potential extrahepatic target tissues. The known theta-specific substrates methyl chloride (MC) dichloromethane and 1,2-epoxy-3-(p-nitrophenoxy)propane (EPNP) were used to assay GSTT1-1 activity in liver and kidney of rats, mice, hamsters and humans differentiating the three phenotypes (non-conjugators, low conjugators, high conjugators) seen in humans. In addition GSTT1-1 activity towards MC and DCM was determined in human erythrocytes. No GSTT1-1 activity was found in any tissue of non-conjugators (NC). In all organs high conjugators (HC) showed twofold higher activity towards MC and DCM than low conjugators (LC). The activity in human samples towards EPNP was too close to the detection limit to differentiate between the three conjugator phenotypes. GSTT1-1 activity towards MC was two to seven-times higher in liver cytosol than in kidney cytosol. The relation for MC between species was identical in both organs: mouse > HC > rat > LC > hamster > NC. In rats, mice and hamsters GSTT1-1 activity in liver cytosol towards DCM was also two to seven-times higher than in the kidney cytosol. In humans this activity was twice as high in kidney cytosol than in liver cytosol. The relation between species was mouse > rat > HC > LC > hamster > NC for liver, but mouse > HC > LC/rat > hamster/NC for kidney cytosol. The importance to heed the specific environment at potential target sites in risk assessment is emphasized by these results.

Animals↗
PubMed2005

Formation of CH3TiX, CH2=TiHX, and (CH3)2TiX2 by reaction of methyl chloride and bromide with laser-ablated titanium atoms: photoreversible alpha-hydrogen migration.

The simple methylidene (CH2=TiHX) and Grignard-type (CH3TiX) complexes are produced by reaction of methyl chloride and bromide with laser-ablated Ti atoms and isolated in a solid Ar matrix, and they form a persistent photoreversible system via alpha-hydrogen migration between the carbon and titanium atoms. The Grignard-type product is transformed to the methylidene complex upon UV (240 nm < lambda < 380 nm) irradiation and vice versa with visible (lambda > 530 nm) irradiation. More stable dimethyl dihalide complexes [(CH3)2TiX2] are also identified, whose relative concentration increases upon annealing and at high methyl halide concentration. The reaction products are identified with three different groups of absorptions on the basis of the behaviors upon broadband photolysis and annealing, and the vibrational characteristics are in a good agreement with DFT computation results.

Journal Article↗