Spectral evidence for the cytochrome P450 nature of prostacyclin synthetase.
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Biomedical subjects
Publications and source records attributed to L Castle.
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Hypotension with lightheadedness and near syncope occurred in three patients during effective ventricular pacing. Hemodynamic studies demonstrated a decrease in cardiac output ranging from almost no decrease to 15 percent, presumably related to the loss of effective atrial contraction. The decrease in output was too small to explain by itself the reduced blood pressure, which resulted from paradoxic reduction of total peripheral resistance in one patient and from failure of resistance to increase in two. Baroceptor reflexes (Valsalva response) were normal in all three patients; hence it is suggested that the failure of compensatory increases in total peripheral resistance may be due to a reflex from the sudden atrial distension that occurs during atrioventricular (A-V) dissociation. The fluctuations in arterial pressure during ventricular pacing were synchronous with the appearance of cannon waves in the right atrial pressure tracing. Arterial pressure during A-V dissociation thus appears to be balanced by two opposite reflexes: the baroceptor reflex, which attempts to compensate for reduction in output, and atrial distension, which reduces peripheral resistance.
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Migration of di-(2-ethylhexyl)adipate (DEHA) into a diverse range of foods arising from the domestic use of plasticized PVC films has been determined using a stable isotope dilution GC/MS procedure. Aspects of home use reported in this study include the wrapping and covering of foods such as cheese, cooked meats, sandwiches, cakes, fresh fruit and vegetables; the use of films during food preparation such as marinading; covering during microwave reheating of previously prepared foods, and covering during microwave cooking. Contact between film and foods was for differing temperatures and times, representative of the range of conditions likely to be experienced in practice in the home. Migration increased with both the length of contact time and temperature of exposure, with the highest levels observed where there was a direct contact between the film and food, and where the latter had a high fat content on the contact surface. Highest levels of migration were observed for cheese, cooked meats, cakes and for microwave-cooked foods, whilst lower levels were observed for wrapping of unfilled sandwiches, fruit and vegetables (except avocado), and for food preparation including microwave reheating where there was covering of the food in a container but little or no direct contact.
A UK survey of di-(2-ethylhexyl)adipate (DEHA) levels in retail foods (83 samples) wrapped in plasticized PVC film has been carried out, examining a wide range of different food types obtained from retail and take-away outlets. Foodstuffs analysed included fresh meat and poultry, ready-cooked poultry, cheese, fruit, vegetables and baked goods such as cakes, bread rolls and sandwiches. Analysis by stable isotope dilution GC/MS showed DEHA levels ranging from 1.0 to 72.8 mg/kg in uncooked meat and poultry, 9.4 to 48.6 mg/kg in cooked chicken portions, 27.8 to 135.0 mg/kg in cheese, less than 2.0 mg/kg in fruit and vegetables and 11 to 212 mg/kg in baked goods and sandwiches. The level of DEHA migration correlated with the extent of contact between the film and exposed fatty portions of the food, whether that was the mayonnaise filling of a sandwich or the surface fat from a joint of uncooked meat. The level of DEHA in meat exposed to plasticized film was not reduced significantly by volatilization or chemical transformation on subsequent cooking by grilling or frying.
A UK survey of plasticizer levels in retail foods (73 samples) wrapped in plasticized films or materials with plasticized coatings has been carried out. A wide range of different food-types packaged in vinylidene chloride copolymers (PVDC), nitrocellulose-coated regenerated cellulose film (RCF) and cellulose acetate were purchased from retail and 'take-away' outlets. Plasticizers found in these films were dibutyl sebacate (DBS) and acetyl tributyl citrate (ATBC) in PVDC, dibutyl phthalate (DBP), dicyclohexyl phthalate (DCHP), butylbenzyl phthalate (BBP), and diphenyl 2-ethylhexyl phosphate (DPOP) in RCF coatings, and diethyl phthlate (DEP) in cellulose acetate. Foodstuffs analysed included cheese, pate, chocolate and confectionery products, meat pies, cake, quiches and sandwiches. Analysis was by stable isotope dilution GC/MS for DBP, DCHP and DEP, GC/MS (selected ion monitoring) for BBP and DPOP, and GC with flame ionization detection for DBS and ATBC, but with mass spectrometric confirmation. Levels of plasticizers found in foods were in the following ranges: ATBC in cheese, 2-8 mg/kg; DBS in processed cheese and cooked meats, 76-137 mg/kg; 76-137 mg/kg; DBP, DCHP, BBP, and DPOP found individually or in combination in confectionery, meat pies, cake and sandwiches, total levels from 0.5 to 53 mg/kg; and DEP in quiches, 2-4 mg/kg.
It has been demonstrated that on storage of a tightly wound reel of polypropylene packaging film, specially printed for experimental purposes, transfer can occur of components from the ink on the outer surface of the film on to the inner food contact surface. For dicyclohexyl phthalate this transfer amounted to 6% of the total amount of plasticizer available in the printing ink system. It was subsequently shown for confectionery and snack food products wrapped in commercially printed polypropylene films that plasticizers only present in the printing ink migrated into the foods. The migration of plasticizer increased with storage time of the wrapped product; for dibutyl phthalate, for example, levels increased from 0.2 to 6.7 mg/kg over the period from 0 to 180 days storage of a chocolate-coated confectionery product. A small retail survey (47 samples) of confectionery, snack products and biscuits wrapped in printed polypropylene film showed the presence of one or more plasticizers at levels from 0.02 to 14.1 mg/kg for dibutyl phthalate, from less than 0.01 to 18.6 mg/kg for dicyclohexyl phthalate and from less than 0.01 to 1.8 mg/kg for di(2-ethylhexyl) phthalate. In all cases there was a good correlation between the plasticizers found in the printing ink from the film and those in the food. Wide variations were found, however, in the amounts and types of plasticizers used in printed packaging of the same brand of retail food product purchased from different regions of the country.
Epoxidised soya bean oil (ESBO) is used as a plasticiser and heat stabiliser in a number of feed contact materials, in particular in poly(vinyl chloride) (PVC) films and gaskets. The level of ESBO migration into foods has been determined using a combined gas chromatographic/mass spectrometric (GC/MS) analytical procedure. The study has included both the use of ESBO-containing materials for retail packaged foods and the domestic use of plasticised PVC films for applications such as wrapping food and covering food for re-heating in a microwave oven. Levels of ESBO in fresh retail meat samples wrapped in film ranged from less than 1 to 4 mg/kg, but were higher (max. 22 mg/kg) in retail cooked meat. Migration into sandwiches and rolls from 'take-away' outlets ranged from less than 1 to 27 mg/kg depending on factors such as the type of filling and the length of the contact time prior to analysis. The levels of migration of ESBO into cheese and cakes were consistent with previous experience with plasticiser migration--direct contact with fatty surfaces leading to the highest levels. When the film was used for microwave cooking in direct contact with food, levels of ESBO from 5 to 85 mg/kg were observed, whereas when the film was employed only as a splash cover for re-heating foods, ESBO levels ranged from 0.1 to 16 mg/kg. For a variety of baby foods there was no significant difference in ESBO levels between foods packaged in glass jars with PVC gaskets and foods in cans containing ESBO in the can lacquer. In both cases ESBO levels were low, ranging from less than 0.1 to 7.6 mg/kg. It is not clear for these retail samples, if the low levels observed (average 1.9 mg/kg) result solely from migration or contain some contribution from naturally occurring epoxides.
Concentrations of benzene of 29 and 64 mg/kg were found in two samples of thermoset polyester compounded for the manufacture of plastic cookware. In collaboration with the suppliers of the materials, it was established that the benzene originated from the use of t-butyl perbenzoate used as an initiator in the manufacture of the polymer. Samples of thermoset polyester made to the original formulations and thus contaminated with benzene showed migration levels of 1.9 and 5.6 mg/kg in olive oil after extraction for 1 hour at 175 degrees C. Migration levels into olive oil at 175 degrees C for samples produced with non-aromatic initiator were less than 0.1 mg/kg. Concentrations of benzene in thermoset polyester cookware purchased from retail outlets were 0.3 to 84.7 mg/kg. Low amounts of benzene (less than 0.01 to 0.09 mg/kg) were detected in foods when the articles were used for cooking in microwave or conventional ovens. Other plastics used for retail food packaging, such as polystyrene and PVC, which might utilise t-butyl perbenzoate catalyst, were also analysed for benzene. Levels were mostly below 0.1 mg/kg, with the highest amounts detected being from 0.2 to 1.7 mg/kg, predominantly in articles of expanded polystyrene.
The diffusion coefficient of the plasticizer di-(2-ethylhexyl)adipate (DEHA) in Cheddar cheese (Df) was determined by measuring the extent to which DEHA penetrated cheese that was placed in intimate contact with artificially DEHA-contaminated cheese. Slices (20 microns) of cheese from the boundary layer, into which DEHA had migrated, were microtomed at -40 degrees C, and analyzed for DEHA by gas chromatography (GC). Mean values of Df determined by graph fitting experimental and calculated data were 1.5 x 10(-9) cm2 s-1 at 5 degrees C and 3.0 x 10(-8) cm2 s-1 at 25 degrees C. The partition coefficient (K) of DEHA between cheese and PVC film was derived from the partition coefficients of DEHA between acetonitrile (ACN) and cheese lipid, ACN and cheese solid, and ACN and PVC film. The mean values of K between cheese and PVC film were estimated to be 0.70 at 5 degrees C and 0.58 at 25 degrees C. The estimated values of Df and K were then used in a mathematical model (Till et al. 1982) to predict migration levels of DEHA into cheese. Good agreement with previously published experimental data was obtained. Extrapolation of the prediction of DEHA migration into fatty foods, such as salami and avocado, was also successful (ratio of experimental to predicted results within a factor of two). The values of Df and K for cheese are, however, inappropriate for modelling non-fatty foods such as meat, cakes, fruit and vegetables. Predicted values for these foods were typically 3-10-fold too high. More accurate predictions would probably be obtained if values of Df more relevant to these foods are used. The predictions were relatively insensitive to the value of K.
Milk samples were collected from a dairy in Norway at various stages of the milking process in order to assess the extent of migration of di(2-ethyl hexyl)phthalate (DEHP) from plasticized tubing used in commercial milking equipment. In control milk samples obtained by hand milking, DEHP contamination was below 5 micrograms/kg, whilst for machine milking, concentrations in the milking chamber for each individual cow averaged 30 micrograms/kg and rose to 50 micrograms/kg in the central collecting tank. Retail pasteurized skimmed milk samples from Norway were found to contain 20 micrograms/kg DEHP, and two retail cream samples contained 1200 and 1400 micrograms/kg of DEHP, reflecting the association of plasticizer with the fat phase. Retail whole milks from the UK contained 35 micrograms/kg of DEHP. This contamination is believed to originate from environmental sources as DEHP plasticizer was not used in the milking equipment.
Temperatures have been measured using a fluoro-optic probe at the food/container or food/packaging interfaces as appropriate, for a range of foods heated in either a microwave or a conventional oven. Reheating ready-prepared foods packaged in plastics pouches, trays or dishes in the microwave oven, according to the manufacturers' instructions, resulted in temperatures in the range 61-121 degrees C. Microwave-active materials (susceptors) in contact with ready-prepared foods frequently reached local spot temperatures above 200 degrees C. For foods cooked in a microwave oven according to published recipes, temperatures from 91 degrees C to 200 degrees C were recorded, whilst similar temperatures (92-194 degrees C) were attained in a conventional oven, but over longer periods of time. These measurements form the basis for examining compliance with specific and overall migration limits for plastics materials. The testing conditions proposed depend on the intended use of the plastic - for microwave oven use for aqueous foods, for all lidding materials, and for reheating of foods, testing would only be required with aqueous simulants for 1 h at 100 degrees C; for unspecified microwave oven use, testing with olive oil would be required for 30 min at 150 degrees C; and for unspecified use in a conventional oven testing with olive oil would be required for 2 h at 175 degrees C. For microwave-active materials, it is proposed that testing is carried out in the microwave oven using a novel semi-solid simulant comprising olive oil and water absorbed onto an inert support of diatomaceous earth. The testing in this instance is carried out with the simulant instead of food in a package and heating in the microwave oven at 600 W for 4 min for every 100 g of simulant employed. There is an option in every case to test for migration using real foods rather than simulants if it can be demonstrated that results using simulants are unrepresentative of those for foods. The proposed testing conditions were validated as being realistic by measurement of the specific migration of various components from different plastics into foods under actual conditions of use and comparing with migration into simulants. Migration of plasticizers from PVC and VC/VDC copolymer films was monitored for both microwave reheating and cooking of foods. Total oligomer concentrations were measured from poly(ethylene terephthalate) (PET) trays, and volatile aromatics from thermoset polyester trays, using both types of container in microwave and conventional ovens.(ABSTRACT TRUNCATED AT 400 WORDS)
To assess the significance of migration of polymeric plasticizers into foods, chemical characterization and quantification of individual oligomeric species is required. This paper reports the identification of seven individual oligomers isolated from a poly(butylene adipate) plasticizer. Based on mass spectrometry, NMR and chemical degradation, the oligomers were identified as a series of diol-terminated units ranging from a trimer up to an 11-monomer unit, along with a cyclic tetramer, all in the molecular weight range of 300-1100. A study of the migration of polymeric plasticizer from PVC film into olive oil indicated preferential migration of low molecular weight species. These oligomers which comprised 24% of the parent plasticizer contributed more than 90% of the plasticizer migration with the smallest oligomers migrating 90-fold more readily than the bulk of the plasticizer. From a knowledge of total polymeric plasticizer migration from PVC films under actual conditions of food-use, the abundance of individual oligomers in the foods has been estimated.
Mineral hydrocarbons are used as processing aids at levels between 0.3 and 3% by weight in crystal polystyrene articles, the food contact uses of which include the dispensing of hot and cold beverages from automatic machines as well as in 'fast-food' and catering establishments. The levels of migration of mineral hydrocarbons from polystyrene cups and glasses have been measured into aqueous food simulants as well as lager, beer, cola, sparkling apple juice, lemon barley water, coffee, hot chocolate, tea, lemon tea and chicken soup. For the cold beverages and simulants, no migration above 0.1 mg/kg was observed, and for the hot beverages and simulants no result greater than 0.5 mg/kg. Analysis was by capillary gas chromatography, using hydrocarbon internal standards calibrated against mineral hydrocarbon reference standards.
Karl Fischer titration has been used to eliminate the need to humidity-condition food contact plastics under test for overall migration into olive oil. The water content of the oil is measured before and after the migration test. This direct measure of the loss (or uptake) of water by the test plastic is then used in calculations of the overall migration. The use of Karl Fischer titration gives faster analysis with reduced labour input. The time savings varied from a few days to several weeks depending on the type of plastic. Karl Fischer titration is particularly useful in the high temperature testing of polar plastics where incomplete humidity conditioning can lead to erroneous results. The technique should be equally valuable when employing sunflower oil or the triglyceride HB307 in place of olive oil.
Experiments have been carried out with (a) microwave treatment of plastics followed by migration testing using the food simulant, olive oil, and (b) microwave treatment of plastics in direct contact with an organic extractant (iso-octane). In neither of these complementary approaches was there evidence of any difference in migration from plastics that had been microwave-treated compared with plastics that had received an equivalent thermal treatment. Five plastics commonly employed in microwave applications were tested and oligomers, plasticizer, antioxidant and volatile contaminants were monitored as representatives of typical migration species.
Migration of polyisobutylene from polyethylene/polyisobutylene film into foods has been studied in domestic applications such as wrapping of foods and reheating in a microwave oven. The results of these migration studies were obtained by direct measurement using newly developed analytical methods utilizing nuclear magnetic resonance (NMR) and infra-red (IR) spectroscopy as well as predictively from assessment of loss of polyisobutylene from the film. Total levels of polyisobutylene migration into cheese were found to be 8-10 mg/kg, into cake 1-5 mg/kg, and into sandwiches ranged from < 1 to 4 mg/kg. Reheating foods covered with film in the microwave oven, gave migration levels ranging from < 0.01 mg/kg for contact with steam only, up to 0.5 mg/kg for severe splashing of food onto the film and 4 mg/kg for reheated pizza. Migration of polyisobutylene was shown to be skewed towards the low molecular weight fraction of the additive. In typical films, the molecular weight range of polyisobutylene was shown to be 300-6000 daltons (95% limits) centred on 1300 daltons, whereas the additive that had migrated into cheese was found to range from 130-2200 daltons, centred on 520 daltons.