Lung cancer mortality and iron oxide exposure in a French steel-producing factory.

OBJECTIVE: To study the possible association between iron oxide exposures and lung cancer risk among workers in a French carbon steel-producing factory. METHODS: 16 742 males and 959 females ever employed for at least 1 year between 1959 and 1997 were followed up for mortality from January 1968 to December 1998. Causes of death were ascertained from death certificates. Job histories and smoking habits were available for 99.7% and 72.3% of subjects, respectively. Occupational exposures were assessed by a factory-specific job-exposure matrix (JEM) validated with atmospheric measurements. Standardised mortality ratios (SMRs) were computed using local death rates (external references). Poisson regressions were used to estimate the relative risks (RRs) for occupational exposures (internal references), adjusted on potential confounding factors. RESULTS: Among males, observed mortality was lower than expected for lung cancer compared to the local population (233 deaths, SMR 0.89, 95% CI 0.78 to 1.01) and higher than expected compared to the French population (SMR 1.30, 95% CI 1.15 to 1.48) No lung cancer excess was observed for exposure to iron oxides (RR 0.80, 95% CI 0.55 to 1.17) and no dose-response relationship with intensity, duration of exposure or cumulative index was found. A significant bladder cancer excess was observed among workers exposed to oil mist (RR 2.44, 95% CI 1.06 to 5.60), increasing significantly with intensity, duration of exposure and cumulative index. CONCLUSION: This study did not detect any relationship between exposure to iron oxides and lung cancer mortality. An excess of mortality from bladder cancer was found among workers exposed to oil mist.

Effective adsorption of oil droplets from oil-in-water emulsion using metal ions encapsulated biopolymers: Role of metal ions and their mechanism in oil removal.

Herein, synthesized and compared the three different kinds of hybrid bio-polymeric composites viz., lanthanum embedded chitosan/gelatin (La@CS-GEL), zirconium embedded chitosan/gelatin (Zr@CS-GEL) and cerium embedded chitosan/gelatin (Ce@CS-GEL) in terms of their oil uptake efficiency. The adsorption efficiency was studied under various optimized parameters like contact time, pH, dose, initial oil concentration and temperature. The oil adsorption capacity was found to be 91, 82 and 45% for La@CS-GEL, Zr@CS-GEL and Ce@CS-GEL composites respectively. The metals were used as a bridging material to connect both CS and GEL using the hydrophilic groups to enhance the oil recovery by hydrophobic interaction. Also, the introduction of metal ions on the surface of biopolymers would modify the oil/water properties which in turn, decrease the interfacial tension between oil and water phases. The mechanism of oil uptake was explained using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscope (SEM), energy dispersive X-ray (EDAX) and heat of combustion. The experimental data confirmed Langmuir isotherm as the best fit for oil adsorption process. Thermodynamic parameters such as standard free energy (ΔG°), standard enthalpy (ΔH°) and standard entropy (ΔS°) indicated that the oil adsorption was spontaneous and endothermic. The oil adsorption mechanism was established based on isotherm and thermodynamic models.

The effect of oil components on the physicochemical properties and drug delivery of emulsions: tocol emulsion versus lipid emulsion.

An emulsion system composed of vitamin E, coconut oil, soybean phosphatidylcholine, non-ionic surfactants, and polyethylene glycol (PEG) derivatives (referred to as the tocol emulsion) was characterized in terms of its physicochemical properties, drug release, in vivo efficacy, toxicity, and stability. Systems without vitamin E (referred to as the lipid emulsion) and without any oils (referred to as the aqueous micelle system) were prepared for comparison. A lipophilic antioxidant, resveratrol, was used as the model drug for emulsion loading. The incorporation of Brij 35 and PEG derivatives reduced the vesicle diameter to <100nm. The inclusion of resveratrol into the emulsions and aqueous micelles retarded the drug release. The in vitro release rate showed a decrease in the order of aqueous micelle system>tocol emulsion>lipid emulsion. Treatment of resveratrol dramatically reduced the intimal hyperplasia of the injured vascular wall in rats. There was no significant difference in this reduction when resveratrol was delivered by either emulsion or the aqueous micelle system. The percentages of erythrocyte hemolysis by the emulsions and aqueous micelle system were approximately 0 and approximately 10%, respectively. Vitamin E prevented the aggregation of emulsion vesicles. The mean vesicle size of the tocol emulsion remained unchanged during 30 days at 37 degrees C. The lipid emulsion and aqueous micelle system, respectively, showed 11- and 16-fold increases in vesicle size after 30 days of storage.

Induction of plasmacytomas in genetically susceptible mice with silicone gels.

Silicone gels injected intraperitoneally into strains of mice related to BALB/c develop plasmacytomas in approximately the same numbers and with similar phenotypes as previously obtained with pristane. Silicone gels produce few side effects and are well tolerated for long periods. Silicone gels contain several components that are potentially biologically active: residual vinyl groups and platinum. Microscopic and histological evidence suggests the silicone gel is degraded over a long period of time. Preliminary studies with long chain liquid dimethylpolysiloxanes with viscosities of 1000 cSt and 12,500 cSt have not produced plasmacytomas as yet. The plasmacytomagenic action of the gel appears to be due to the release of liquids from the gel matrix.

Further development of rodent whole embryo culture: solvent toxicity and water insoluble compound delivery system.

In order to study the in vitro embryotoxicity and dysmorphogenesis of water insoluble compounds, solvents or chemical delivery systems of low toxicity and teratogenicity to the developing embryo must be found. Therefore, day 10.5 rat embryos were cultured for 2 days in whole rat serum containing 0.1, 0.5 and 2.5 vol.% of ethyl alcohol, dimethylsulfoxide, acetone, Tween 80, corn oil and 10% acetone/90% corn oil. No adverse effects occurred with any of the solvents at the 0.1% concentration level. At 0.5% ethyl alcohol and Tween 80 significantly reduced embryonic growth and increased the incidence of embryonic abnormalities. With the exception of corn oil and acetone/corn oil, embryos cultured in media containing 2.5% of various solvents failed to grow, did not differentiate, and died during the culture period. Corn oil suspended in rat serum by use of ultrasound was non-toxic even at concentrations of 2.5% and 10%. Growth parameters of embryos cultured in serum containing corn oil were indistinguishable from controls and overall morphogenesis was good (particularly at 2.5%). The order of increasing embryotoxicity and dysmorphogenesis of the studied liquids was corn oil less than acetone/corn oil less than dimethylsulfoxide less than ethyl alcohol, acetone less than Tween 80. Any of the 4 water miscible solvents (at 0.1%) or a sonicated suspension of corn oil in serum (up to 2.5%) met the criteria of a non-toxic and non-teratogenic water insoluble compound delivery system for in vitro embryo culture.

Toxicological evaluation of mixtures of nonionic surfactants, alone and in combination with oil.

The toxicity to human bronchial (16-HBE14o-) epithelium cells of nonionic surfactants, polyoxyethylene-10-oleyl ether (C(18:1)E(10)), polyoxyethylene-10-dodecyl ether (C(12)E(10)), and N,N-dimethyl-dodecylamine-N-oxide (C(12)AO) alone or in combination with a range of pharmaceutically acceptable oils (namely, ethyl esters and triglyceride oils), was determined with the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Regardless of the presence of oil, all C(12)E(10)- and C(12)AO-containing systems were toxic at concentrations around or below their critical aggregation concentrations (as determined by surface tension measurements), suggesting that surfactant toxicity was due to the disruption caused by the partitioning of monomeric surfactant into the cell membrane. Systems prepared from C(18:1)E(10) alone or in combination with a low-molecular-weight oil, such as ethyl butyrate or tributyrin, were toxic above their critical aggregation concentration. In contrast, systems prepared from C(18:1)E(10) in combination with a high-molecular-volume oil (e.g., ethyl oleate, Miglyol 812, or soybean oil) were toxic only at concentrations significantly greater than their critical aggregation concentration, suggesting that in these cases surfactant toxicity was mediated by the aggregated form of the surfactant solubilizing components of the cell membrane. In the C(18:1)E(10)-stabilized system, it is proposed that toxicity was significantly reduced on incorporation of high-molecular-volume oils because these oils cause formation of a distinct oil core in the aggregates that leads to a reduction in the ability of the system to solubilize components of the cell membrane.

[Environmental chemicals: their clinical significance in rheumatology]. / Umweltchemikalien: ihre klinische Bedeutung in der Rheumatologie.

Over the past years, various illnesses including features of connective tissue disorders (e.g. systemic sclerosis, systemic lupus erythematosus, mixed connective tissue disease), and rheumatoid arthritis, seemingly related to exposure to environmental materials have been reported. This paper presents some typical case reports and review major environmental associations seen in rheumatology, along with their epidemiology, clinical and laboratory features, possible pathogenesis, prognosis, and potential therapy.

Embryotoxic effects of phtalic acid derivatives, phosphates and aromatic oils used in the manufacturing of rubber on three day chicken embryos.

Several chemicals that are used for manufacturing of rubber were tested for embryotoxicity on three day chicken embryos. Cyclohexylthiophtalimide was the most potent of the chemicals, with an ED50 value for the total embryotoxic effect 0.04 mumol (10 micrograms) per egg. Phtalic anhydride was about ten times less potent, having the total ED50 for total embryotoxicity 0.38 mumol (56 micrograms) per egg. Two esters of phtalic acid, dibutylphtalate and butylbenzylphtalate, instead, were relatively impotent, with ED50 values of about 33 mumoles and 27 mumoles per egg, respectively. Two phosphates, tricresylphosphate and synthetic arylphosphate, were not potent embryotoxic agents in the chick embryos. They had ED50 values of 7.0 mumoles (2.6 mg) per egg and 9.5 mg per egg, respectively. Sodium phosphate (NaH2PO4) had the ED50 11 mumoles per egg. Three types of oils were tested, too. A mixture known as "highly aromatic oils" was the most potent, with the ED50 31 micrograms per egg. "Low aromatic, paraffin base oils" was the next potent, with the ED50 87 micrograms per egg, while "naphtenic oils" had the ED50 480 micrograms per egg. Cyclohexylthiophtalimide and phtalic anhydride caused malformations at high frequency. The oils and tricresylphosphate appeared to be efficient teratogens under the experimental conditions used.

Cremophor and Emulphor induced alterations of serum lipids and lipoprotein electrophoretic patterns of dogs.

The effects of Cremophor and Emulphor, two polyethoxylated castor oil vehicles, on serum lipids and lipoproteins electrophoretic patterns were examined in beagle dogs. The vehicles were given as daily intravenous (i.v.) infusions of 0.5 ml/kg. Flushing of the skin, edematous wrinkling of the skin above the eyes and shaking of the head were observed during or shortly after each infusion of either vehicle. Thrombocytopenia occurred in Emulphor-treated dogs but increased platelet counts occurred in Cremophor-treated dogs. The spleen, lymph nodes, livers and kidneys all had excessive amounts of lipid present. There were increased serum levels of triglycerides, lipids, cholesterol and lipoproteins. Electrophoresis of sera revealed decreased alpha-lipoprotein fraction and the appearance of a new, as yet unidentified, peak near the origin. The lipid and lipoprotein changes were more marked in dogs treated with Cremophor. It appears that daily infusion with either vehicle results in changes in serum lipids, lipoprotein patterns and tissue lipid content.

18 month skin painting study of a mercapto-functional silicone oil in mice.

Thrice weekly application of lambda-mercapto-polydimethylsiloxane to the shaven backs of Swiss mice over an 18 month period did not have an obvious effect on weight gain nor did this material produce systemic toxicity. Lung adenomas and lymphosarcomas were observed upon histopathological examination in both untreated and treated group. Other lesions observed were not thought to be treatment related.

90-day sub-chronic inhalation toxicity of a mercapto-functional silicone oil in rats.

A mercapto-functional poly(dimethylsiloxane) silicone oil vapor (0.15 and 0.45 mg/l) was generated by passage of air through the heated oil and rats were subjected to these vapors over a 90-day period. An extensive pathological, clinical and hematological workup failed to demonstrate any significant effects of this exposure. In addition, weight gains over the experimental period were comparable to controls.

Effect of silicone oil on the cornea.

Silicone oil can dissolve about seven times more oxygen that can water. Placed in a depot between a rigid scleral lens and the corneal surface, silicone oil might thus be useful for treating severe dry-eye patients and for preventing exposure keratitis. To explore this possibility, generic (300, 500, 1000, and 12,500 cs) and medical-grade (1000 cs) silicone oils were tested on rabbit eyes. When oxygenated silicone oil was placed in a cup formed by the lids and hanging sutures and allowed to remain for 3 h on the eyes of anesthetized rabbits, the immediate reaction was mild epithelial edema. By 3 to 6 days later, the thickness of the epithelium and of the entire cornea had increased irregularly. The most common histologic finding was intracellular epithelial edema, particularly in the basal cell layer. The reaction was most intense for the generic oils of the lowest viscosities. The medical-grade oil was the best tolerated, but it too affected epithelial and corneal thickness. Ultrastructural studies of treated eyes showed abnormal epithelial surfaces but no major changes within the epithelial cells. Biochemical analysis showed some decrease of glycogen in the corneal epithelium of eyes kept under oxygenated medical-grade silicone oil. A smaller decrease of glycogen level persisted after 2 days exposure of the treated eye to air, suggesting that the corneal epithelium was injured by a mechanism other than hypoxia.

The comparative toxicity of operational Air Force hydraulic fluids.

The subchronic (26 day) oral toxicities of two AF hydraulic fluids (MIL-H-5606 [H5], MIL-H-83282 [H8]), a commercial phosphate ester (PE), and two candidate hydraulic fluids (low temperature version of MIL-H-83282 [LT] and chlorotrifluorethylene oligomers [polyCTFE]) were compared in male F-344 rats. Oral dosing was used in order to quickly compare these fluids to PolyCTFE, the only fluid at the time to have been tested in a 90-day inhalation study. Rats were initially dosed with 1.0 g/kg/day of each fluid. H8 increased alkaline phosphatase (ALKP) while LT produced an anemia and leukocytosis. Exposure to H5 fluid resulted in lymphocytopenia and persistent diuresis. Due to their greater toxicity, resulting in lethality in the first dosing study, only 0.5 g/kg/day of PE and PolyCTFE were administered in the second study. Exposure to PE (0.5 g/kg) resulted in an anemia and decreases in BW (day 10 until day 25), spleen/BW ratio, blood urea nitrogen (BUN), and creatinine (CREAT). PolyCREAT (0.5 g/kg) decreased BW (day 11 to the end of the study) and testicular weight. PolyCTFE (0.5 g/kg) increased relative spleen weights, various clinical chemistry parameters, and triggered a reversible diuresis. PolyCTFE (0.5 g/kg), PE (0.5 g/kg), and H5 produced an increase in absolute and relative liver weights compared to control livers. Peroxisomal beta oxidation, an indicator of peroxisomal proliferation, was significantly increased above control levels in the livers of all rats except the PE (0.5 g/kg) group, where the increase was not significant. Hydrocarbon nephropathy, indicated by increased levels of hyaline droplets in kidney tubules, was severe in H5, mild in H8, LT, and PolyCTFE (0.5 g/kg), and minimal in PE (0.5 g/kg). The MIL-H-83282 fluids (H8 and LT) were the least toxic hydraulic fluids. PolyCTFE and PE were the most toxic, with H5 intermediate.