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Toxicity of vinyl chloride and polyvinyl chloride as seen through epidemiologic observations.

In 1974, vinyl chloride (VC) was first reported in the scientific literature to induce angiosarcoma of the liver in animals and humans. Further research has now demonstrated the carcinogenicity of this agent to other organs. Target organs for VC now include the liver, brain, and lung, and probably the lymphohematopoietic system. The carcinogenic risk has been extended to jobs associated with polyvinyl chloride (PVC) exposure. This is evidenced by cases of liver angiosarcoma reported among individuals employed in or residing near PVC fabrication facilities and by epidemiologic study demonstrating a significant association between lung cancer and exposure to PVC dust. An association between PVC dust and pneumoconiosis has been demonstrated. On the basis of these findings, experimental bioassays and epidemiologic studies of the carcinogenicity of PVC are clearly in order. Prudent control of PVC in the industrial setting is also clearly indicated.

Brain Neoplasms↗

Calcium chloride inhibits stimulation of replicative DNA synthesis by sodium chloride in the pyloric mucosa of rat stomach.

Calcium chloride (CaCl2) inhibits stimulation of replicative DNA synthesis (RDS) induced in the pyloric mucosa of male Fischer 344 rats by sodium chloride (NaCl), which is a tumor promoter in the glandular stomach. Administration of 1 ml of 3.3 M NaCl by gastric intubation induced a maximal 15-fold increase in RDS in the pyloric mucosa by 17 h; this had returned to the control level by 48 h. Administration of 1 ml of 20-400 mM CaCl2 1 h before administration of NaCl resulted in a 60-100% inhibition of the increase in RDS within 4-48 h; the inhibition was dose-dependent. The 400 mM level of CaCl2 also decreased the histological damage to surface epithelial cells induced by NaCl. These results suggest that calcium ion acts as an anti-tumor promoter in stomach carcinogenesis.

Animals↗

Effects of vasoconstrictors on isolated rabbit coronary arteries exposed to isotonic iohexol. Potassium chloride-, histamine-, endothelin-, and prostaglandin-F2 alpha-induced contractions on arteries exposed to iohexol without and with osmotic additions (sodium chloride or glucose).

RATIONALE AND OBJECTIVES: A major effect of contrast media (CM) on coronary vessels is vasodilatation, but occasionally, both ionic and nonionic media may cause coronary artery spasm. The influence of CM on the actions of vasoactive substances is not well known. To investigate the effects on rabbit coronary arteries of an iso-osmolar nonionic CM, iohexol (140 mg I/mL) the vasoconstrictors potassium chloride (KCl), histamine, endothelin, and prostaglandin-F2 alpha (PGF2 alpha) were used. The effects of iohexol with 30 to 150 mM sodium chloride (NaCl) or with 25-50 g/L glucose also were investigated. METHODS: Coronary artery segments were mounted between two L-shaped prongs in tissue baths with buffer solution. Before each investigation, buffer was exchanged with iohexol solution. Increasing concentrations of a vasoconstrictor were added, and the constriction of the vessels was recorded. RESULTS: Iohexol caused a comparatively small inhibition of the contractile effects of histamine and endothelin. This meant little reduction in maximal contraction (Emax), and the concentration of constrictory substance resulting in half maximal contraction (EC50) compared with buffer solution. Iohexol also caused a small reduction in Emax of KCl, but EC50 was significantly lower. Adding NaCl or glucose to iohexol decreased Emax and increased EC50. Iohexol inhibited most of the contractile effect of PGF2 alpha, but adding NaCl increased Emax slightly. CONCLUSIONS: The effects caused by a nonionic CM on coronary arteries cannot be attributed to osmolality alone. The CM influenced the effects of vasoconstrictors to differing degrees, but the inhibition of the CM per se was usually small.

Animals↗

Control of Alternaria alternata by cassia oil in combination with potassium chloride or sodium chloride.

AIMS: To compare antifungal effects of cassia oil alone and in combination with potassium chloride (KCl) or sodium chloride (NaCl) against Alternaria alternata in vitro and in vivo. METHODS AND RESULTS: The inhibitory effect of cassia oil alone, or in combination with KCl and NaCl were tested in vitro. The spore germination and germ tube elongation of the pathogen was evaluated in potato dextrose broth with light microscopy analysis. The inhibitory effect of cassia oil alone, or in combination with KCl and NaCl, was determined on cherry tomatoes in vivo. The cassia oil in combination with KCl and NaCl exhibited strong antifungal effect in vivo and in vitro. CONCLUSIONS: The antifungal effect of cassia oil against Alt. alternata was enhanced significantly by combining with KCl and NaCl both in vitro and in vivo. SIGNIFICANCE AND IMPACT OF THE STUDY: The combination of cassia oil and KCl or NaCl may enhance antifungal effect of cassia oil and reduce cost.

Alternaria↗

Changes in pulmonary function in workers exposed to vinyl chloride and polyvinyl chloride.

To determine whether occupational exposure to vinyl chloride gas and polyvinyl chloride dust is associated with changes in pulmonary function, spirometry and maximum expiratory flow-volume curves were obtained in 348 workers in a VC polymerization plant. The major finding was diminution in air flow in 200 workers (57.5 percent). This abnormality correlated with age and duration of exposure. A relationship with smoking was noted only in younger workers with exposures of less than 10 years. When age exceeded 40 years or exposure 20 years, prevalence of this impairment was similar in smokers and nonsmokers, suggesting that occupational or other environmental factors were operative.

Adult↗

Pathology of angiosarcoma of the liver among vinyl chloride-polyvinyl chloride workers.

We described the histologic features of 13 hepatic angiosarcomas which developed in workers engaged in the polymerization of vinyl chloride to polyvinyl chloride. Although the histologic features varied considerably in different portions of the angiosarcoma in the same liver and in the angiosarcomas of the liver from different patients, many features were similar such as sinusoidal, papillary, and cavernous growth patterns coincident with the precursor lesions of proliferation and atypia of sinusoidal lining cells.

Hemangiosarcoma↗

Sodium chloride, potassium chloride, and virulence in Listeria monocytogenes.

Virulence, as determined in a mouse model, and the virulence factor activities of catalase, superoxide dismutase, and listeriolysin O were examined in a parental strain (10403S) and in a nonhemolytic mutant strain (DP-L224) of Listeria monocytogenes. The cells were propagated in media containing various concentrations of sodium chloride or potassium chloride. Strains 10403S and DP-L224 exhibited significant increases in catalase activity and listeriolysin O activity when grown in medium containing either salt at 428 mM. The superoxide dismutase activities for both strains increased when they were grown in medium containing either salt. The superoxide dismutase activity was significantly increased only when cells were propagated in medium containing no salt compared with that when they were propagated in medium containing either salt at 1,112 mM. In addition, the listeriolysin O activity was highest for cells propagated in medium containing KCl at 428 mM, while the activity was significantly less for cells propagated in medium containing NaCl at an equal concentration. Virulence was examined in mouse livers and spleens after intravenous infection, and approximate 50% lethal doses were determined after intragastric and intraperitoneal infection. Each method of infection indicated that listeriolysin O is required for virulence, while growth in salt-containing medium or the production of higher levels of catalase, superoxide dismutase, and listeriolysin O do not appear to enhance the virulence of L. monocytogenes.

Animals↗

Occupational asthma due to soft corrosive soldering fluxes containing zinc chloride and ammonium chloride.

Two cases of occupational asthma due to soft corrosive soldering fluxes used in metal jointing are described in which the diagnosis was based on work related deterioration in daily peak expiratory flow rate and positive responses in bronchial provocation tests. Both fluxes contained ammonium chloride and zinc chloride. Occupational asthma provoked by these agents has not previously been reported.

Adolescent↗

Worker exposure to vinyl chloride and poly(vinyl chloride).

The National Institute for Occupational Safety and Health (NIOSH) in early 1974 began industrial hygiene studies of vinyl chloride exposed workers. Three VC monomer plants, three VC polymerization plants, and seven PVC fabrication plants were surveyed. V polymerization plant workers and workers in one job category in VC monomer plants were exposed to average levels above 1 ppm. The highest average exposure was 22 ppm. NIOSH health hazard evaluation studies since these initial surveys have primarily shown nondetectable levels of vinyl chloride. A NIOSH control technology study in 1977 showed that exposure levels in VC polymerization plants had been drastically reduced but exposure levels above 1 ppm were still found in several cases.

Air Pollutants↗

Review of pulmonary effects of poly(vinyl chloride) and vinyl chloride exposure.

The contributions of several recent reports to the definition of pulmonary effects of PVC dust inhalation are reviewed. Granulomatous reaction, with inclusion of PVC particles in macrophages and histocytes, and associated interstitial pulmonary fibrosis have been found to lead to exertional dyspnoea, diffuse micronodular chest radiographic opacities and restrictive pulmonary dysfunction. The effects of vinyl chloride (VC) monomer (gas) on proteins and the immunologic mechanisms triggered by the altered protein are possible mechanisms for the development in some cases of interstitial pulmonary fibrosis secondary to VC exposure. Vinyl chloride, a confirmed carcinogen, has been associated with, among other malignant tumors, a significant increase in the incidence of lung cancer. The magnitude of this effect has not yet been completely evaluated.

Dust↗

Effects of postexsanguination vascular infusion of cattle with a solution of saccharides, sodium chloride, and phosphates or with calcium chloride on quality and sensory traits of steaks and ground beef.

Grain-finished Hereford x Angus steers (n = 36) were assigned to one of three treatmentgroups. Immediately after jugular exsanguination, 12 steers were infused at 10% of live weight via the left carotid artery with a solution developed by MPSC, Inc. (St. Paul, MN) consisting of 98.52% water, 0.97% saccharides, 0.23% sodium chloride, and 0.28% phosphate blend (MPSC); 12 steers were infused at 10% of live weight with 0.30 M CaCl2 (CaCl2); and 12 steers were exsanguinated conventionally and served as noninfused controls (CON). Declines in pH for three muscles were measured. CaCl2-infused carcasses exhibited extensive muscle contraction at the time of cooler entry. Carcasses were graded at 24 h postmortem and fabricated at 48 h postmortem. Longissimus lumborum (LL), semitendinosus (ST), and quadriceps femoris (QF) muscles were removed, vacuum packaged, and stored at 2 degrees C until 14 d postmortem. Then, 2.54-cm-thick steaks were cut from the LL and ST for shear force and sensory evaluations. Ground beef was formulated from the QF to contain 20% fat. Steers infused with MPSC and CaCl2 had 4.0 and 2.3% higher dressing percentage points, respectively, than CON steers. Calcium concentrations of the LL muscle for CaCl2- and MPSC-infused carcasses, as well as the CON carcasses, were 892.0, 158.9, and 216.6 ppm, respectively. For the TB and longissimus thoracis muscles, pH decline was more rapid for CaCl2- and MPSC-infused carcasses than for CON carcasses, but there were no differences in 24-h pH. Warner-Bratzler shear force values were much higher (P < 0.05), and descriptive attribute sensory panel tenderness scores much lower (P < 0.05), for the LL from CaCl2-infused carcasses than for MPSC-infused and CON carcasses. Flavor intensity of the LL of CaCl2-infused carcasses was reduced (P < 0.05); however, overall tenderness and flavor of the ST were unaffected (P > 0.05) by CaCl2 infusion. Beef flavor identification, brown-roasted flavor, and bloody/serumy flavor were lowest and soapy/chemical flavor was highest (P < 0.05) for both freshly cooked and warmed-over LL from CaCl2-infused carcasses. There were no distinct meat quality advantages for infusing cattle with a solution of saccharides, sodium chloride, and phosphates. Infusion with 0.30 M CaCl2 increased dressing percentage, but caused severe muscle contraction early postmortem, decreased LL tenderness markedly, and reduced flavor of LL steaks and ground beef.

Animals↗

High chronic ambient temperature stress effects on broiler acid-base balance and their response to supplemental ammonium chloride, potassium chloride, and potassium carbonate.

Four experiments were conducted to evaluate the effect of heat stress on acid-base status and the birds' response to supplemental KCl and KCO3. The corn-soybean meal fish-meal basal ration (.73% K+) contained more K+ and Cl- than is recommended by the National Academy of Sciences for chicks reared under near optimal conditions (24 C and 55% relative humidity). Chicks reared under continuous thermostress (35 C, 70% relative humidity) exhibited panting phase blood alkalosis (pH of 7.46). Supplementing drinking water with .2% NH4Cl reduced panting phase blood pH to normal values and increased live weight gain (23%) and feed efficiency (7.7%). Supplementing drinking water with .15% KCl also increased (P less than .05) live weight gain (46%) and feed efficiency (15.4%) but did not affect (P less than .46) blood pH. A significant (P less than .01) interaction existed between NH4Cl and KCl for body weight gain. Adding .2% NH4Cl to broiler drinking water reduced the level of KCl required in drinking water to optimize weight gain to .1% KCl. Potassium chloride alone, or with NH4Cl, can alleviate some consequences of heat stress, but supplementing drinking water with a high level of NH4Cl (.5%) decreased (P less than .05) blood pH to acidotic levels and reduced body weight gain. Potassium chloride supplementation exacerbated NH4Cl toxicity. Potassium carbonate reduced (P less than .05) body weight gain indicating that the response may not be attributed to K+ alone. Beneficial effects of NH4Cl therapy for heat stressed broilers are speculative.

Acid-Base Equilibrium↗

Gas-liquid chromatographic determination of vinyl chloride in vinyl chloride polymers, food-simulating solvents, and other samples.

The determination of vinyl chloride (VC) in polyvinyl chloride (PVC), vegetable oils, food-simulating solvents, mouthwashes, and blood anticoagulant solutions by gas-liquid chromatography is described. PVC polymers are disolved in either tetrahydrofuran or dimethyl acetamide. Vegetable oils are diluted with an equal volume of tetrahydrofuran. The resulting solutions are injected into a gas-liquid chromatograph equipped with a flame ionization detector. Mouthwashes, blood anticoagulant solutions, and 3 food-simulating solvents, 3% acetic acid, 50% ethanol, and heptane, are analyzed by direct injection into a chromatograph. Sensitivities are such that 0.05 ppm VC in solution or 1 ppm VC in PVC can be quantitated.

Anticoagulants↗

[Respiratory function study of workers engaged in vinyl chloride and polyvinyl chloride manufacture].

A hygienic evaluation is made on the work conditions in the production of vinyl chloride and polyvinyl chloride. Studies were carried out on 516 workers after the following indices: vital capacity /VC/, forced expiratory volume per sec. /FEV1/, peak expiratory capacity /PEC/, maximum expiratory capacity 75 /MEC75/, maximum expiratory capacity 50 /MEC50/ and maximum expiratory capacity 25 /MEC25/. It was established that 33.13% of the workers were with ventilation disturbances. The most frequently met was the obstructive syndrome of ventilation insufficiency. The infringements were most often in workers with length of service up to 1 year.

Adult↗

[Antiarrhythmic action of 3-carbethoxyamino-5-dimethylaminoacetyl-iminodibenzyl hydrochloride (Bonnecor, AWD 19-166, GS -15) on experimental arrhythmia induced by aconitin, ouabain, calcium chloride and barium chloride].

In comparison with detajmium, prajmalium, ajmaline, quinidine, lidocaine, disopyramide, propranolol, and Ethmozin the substance GS 015 is tested on the aconitin-induced arrhythmia of the rat, the auricular fibrillation by aconitin of the dog, the ventricular arrhythmia induced by ouabaine of the dog, the arrhythmia caused by calcium chloride of the rat, and the arrhythmia induced by barium chloride of the rabbit. The particular qualities of effect in the special forms of arrhythmia are discussed in connection with the study of the antiarrhythmic action in case of coronary occlusion, with the increase of the electric fibrillatory threshold, and with the electrophysiologic tests.

Aconitine↗

Headspace sampling and gas-solid chromatographic determination and confirmation of greater than or equal to 1 ppb vinyl chloride residues in polyvinyl chloride food packaging.

The determination and confirmation of residual vinyl chloride (VC) in polyvinyl chloride (PVC) food packaging materials are described. PVC packaging materials are dissolved in dimethylacetamide (DMAC). VC is sparged from solution with helium gas and collected in sealed vials of ethanol. VC is detected and quantitated by using a headspace sampling technique and standard gas-solid chromatography (GSC) with flame ionization detection. GSC peak heights of about 5% full scale deflection are obtained for samples of PVC containing 1 ppb VC. Polymer samples taken from tubing, blood bags, food packaging films, bottles, and unprocessed resin were analyzed. Residual VC levels ranged from 0.3 to 913 ppb. VC was confirmed by GSC-mass spectrometry, using selected ion recording of m/z 62 and 64 in conjunction with full mass scans to identify components eluting near VC.

Chromatography, Gas↗

Dose-dependent promotion effects of potassium chloride on glandular stomach carcinogenesis in rats after initiation with N-methyl-N'-nitro-N-nitrosoguanidine and the synergistic influence with sodium chloride.

The modifying effects of potassium chloride (KCl) ingestion on glandular stomach carcinogenesis were investigated in male Wistar rats induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and were compared with those of sodium chloride (NaCl). A total of 120 male 6-week-old Wistar rats were divided into six groups, each consisting of 20 animals. After initiation of treatment with a MNNG solution (100 parts/million) as their drinking water for 10 weeks, rats were fed a diet supplemented with 5% NaCl, 2.5% NaCl, 2.5% NaCl plus 2.5% KCl, 5% KCl, 2.5% KCl, or a basal diet alone for the following 62 weeks. Under this experimental condition, there were no statistical differences in the final body weights between groups. The incidences of adenocarcinomas in the glandular stomachs were significantly higher in the 5% NaCl and combined 2.5% NaCl-plus-2.5% KCl groups (P < 0.05 and 0.01) than in the MNNG alone (control) group. The incidences of atypical or precancerous hyperplasias in the glandular stomachs were increased significantly by the 5% NaCl, 2.5% NaCl-plus-2.5% KCl, and 5% KCl treatments (P < 0.05 or 0.01). The multiplicities of adenocarcinomas were significantly greater in the 5% NaCl, 2.5% NaCl, and combined NaCl-plus-KCl groups (P < 0.05 or 0.01) compared with the control value. The multiplicity data for atypical hyperplasias were most striking; namely, their multiplicities were increased significantly by the treatments of NaCl or KCl (P , 0.01) in a clear dose-dependent manner and enhanced synergistically by the combined treatment of NaCl and KCl. Because the concentrations of KCl used in this study were about 1.3 times lower than those of NaCl on a molar basis, although the doses of each chemical were exactly the same on a weight-percent basis, it is suggested that the enhancing effects of KCl might not be much different from those of NaCl. The results in the present study thus indicate that, similarly to NaCl, KCl ingestion exerts dose-dependent promoting effects and a synergistic influence with NaCl when given during the postinitiation phase of two-stage glandular stomach carcinogenesis in rats.

Animals↗

Mortality and cancer morbidity in workers exposed to low levels of vinyl chloride monomer at a polyvinyl chloride processing plant.

To study whether exposure to low levels of vinyl chloride monomer (VCM) causes increased risk for cancer morbidity and death from ischemic heart disease, a cohort study was performed among 2,031 male workers at a polyvinyl chloride (PVC) processing plant who had been employed for at least 3 months during the period 1945-1980. An almost significantly increased total mortality (SMR = 116, 95% CI 99-136) was found. Deaths caused by violence or intoxication were significantly increased (SMR = 153, 95% CI 109-213), but not deaths from ischemic heart disease (SMR = 100, 95% CI 73-135). A significant increase in total cancer morbidity was observed (SMR = 128, 95% CI 101-161). Respiratory cancers were significantly increased (SMR = 213, 95% CI 127-346). Furthermore, six brain tumors (vs. 2.6 expected) were observed. This increase, however, was not significant (SMR = 229, 95% CI 84-498). No liver hemangiosarcoma was observed. Applying a latency period of greater than or equal to 10 years from start of employment did not change the risk patterns. There were no significant exposure-response associations between exposure estimates for VCM, asbestos, and plasticizers and cancer morbidity.

Adult↗