Biomedical subjects
Publications and source records attributed to G Ellen.
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The contents of cadmium, lead mercury, copper, manganese and zinc in 242 samples of 37 different species of domestic and imported fruits have been determined. Also contents of the same heavy metals, except mercury, have been determined in 205 samples of 7 species of domestic vegetables (lettuce, spinach, endive, beetroots, onions, celeriac and Swedish turnips). The median contents (in mg/kg fresh mass of the edible part) found for fruits are: Cd 0.002; Pb 0.017; Hg 0.002; Cu 0.61; Mn 0.52 and Zn 0.99. In the vegetables median levels have been found (mg/kg) of 0.009-0.073 for Cd, 0.01-0.03 for Pb, less than 0.2-0.3 for Cu, 0.69-1.41 for Mn and 0.95-5.5 for Zn. The contribution of fruits to the tolerable daily intakes of Cd, Pb and Hg is, for an average consumption pattern, less than 1%. On the other hand, the contribution to the recommended amounts of the essential elements Cu, Mn, and Zn is no more than 1%-3%. From the vegetables an average portion of spinach contains 19% and 2.6% of the tolerable daily amounts of Cd and Pb, respectively. For the other species of vegetables these figures are less than 5% for Cd (except for endive, 6.8%) and for lead less than 1%. Spinach contributes considerably to the need for Cu, Mn and Zn, in general more than 10% of the recommended daily amounts. The other species of vegetables contribute only from less than 1% to less than few percents.
A two-year-old male Barsoi dog was presented after a two-week period of muscle twitching and convulsions during exercise, which worsened to a state of tetraparesis and coma. Removal of a gastric foreign body, containing aluminium, resolved the presenting signs. Parallel with this clinical recovery the elevated serum levels of aluminium decreased to values of two normal control dogs, suggesting that the neurological signs were due to A1 intoxication.
Kidneys of cattle, pigs and sheep and chicken livers have been analyzed for contents of copper, chromium, manganese, nickel and zinc. Mean levels found for copper, manganese and zinc correspond well with results of earlier studies as well as with literature data. Contents measured for chromium and nickel are very low: for nickel in porcine kidneys and sheep kidneys median values of 0.045 and 0.022 mg/kg were found. Average contents for nickel in the other tissues and for chromium in all tissues investigated are below 0.01 mg/kg fresh mass. These results for chromium and nickel correspond well with recent results from Sweden, but are lower than most published values.
In 1983 and 1985, rubber teats and pacifiers from the Dutch market were analysed for N-nitrosamines (NA) and nitrosatable compounds (NC) by extraction with an artificial saliva test solution (24 h, 40 degrees C). NC were determined as NA (gas chromatography-thermal energy analysis) after nitrosation. In 1983, the total content of NA and NC varied from 4-40 micrograms/kg and 50-3700 micrograms/kg, respectively (18 samples). In 1985, NA and NC varied from 3-94 micrograms/kg and 26-5100 micrograms/kg, respectively (20 samples). According to Dutch legislation, teats may contain no more than 1 microgram/kg and 20 microgram/kg NA and NC. Of other rubber and plastic commodities analysed, balloons contained levels of up to 120 micrograms/kg and 2800 micrograms/kg NA and NC.
A large number of organs of slaughtered animals were examined for heavy metals, arsenic and selenium during the period from 1970 to 1980. In the present paper, the arsenic, cadmium, mercury, lead and selenium levels determined in porcine and bovine kidneys and livers as well as in porcine brain are reviewed. The following median levels (in mg/kg of fresh product) of the various elements were determined: (table; see text) In a number of cases, organs and meat from the same animal were studied; the levels in meat were much lower than those in organs in every case. A constant ratio between the levels of the elements in meat and those in organs was not observed.
A total of 140 samples of 16 kinds of cured meats were analyzed for contents of residual nitrite and N-nitrosamines. Nitrite was determined by reaction with sulfanilamide/naphthylethylenediamine and colorimetric measurement. N-nitrosamines were isolated from the samples by vacuum distillation and determined by gas-chromatography with chemiluminescence detection (GC-TEA). In six samples no nitrite was detectable (less than 1 mg NaNO2/kg), the remaining samples contained 1-140 mg NaNO2/kg, median value 6.8 mg/kg. In 46 samples (33%) no N-nitrosamines were detected, i.e. less than 0.1-0.5 microgram/kg of the individual nitrosamines, depending upon their structure. N-nitrosodimethylamine (NDMA) was the nitrosamine present most frequently, in 75 samples, contents were 0.1-0.9 microgram/kg, mean 0.3 microgram/kg. Other N-nitrosamines found were: N-nitrosopiperidine (NPIP), 10 times, 0.3-25 micrograms/kg; N-nitrosodiethylamine (NDEA), three times, 0.2-0.9 microgram/kg; N-nitrosopyrrolidine (NPYR), three times, 1.3-4.2 micrograms/kg; N-nitrosomorpholine, once, 0.7 microgram/kg and N-nitrosothiazolidine (NTHZ), 36 times, 0.5-91 micrograms/kg, mean 5.7 micrograms/kg. NTHZ was found most often and with the highest contents in smoked products. Frying of bacon and cured, smoked pork bellies led to substantially increased levels of NPYR in both products, and for the pork bellies also of NTHZ. In five samples of cured, smoked pork bellies after frying NTHZ-contents of 3.6-490 micrograms/kg (mean 179) were found. No correlation between residual nitrite levels and N-nitrosamine contents could be established. Investigations during the nineteen seventies gave much higher levels for NDMA, NDEA, NPIP and NPYR in Dutch cured meats than now found; at that time NTHZ was not measured.
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Urines from 12 healthy volunteers, sampled from 0-24 h after the volunteers had been administered 9.5 g sodium nitrate intravenously or up to 10.5 g ammonium nitrate orally, were analysed for N-nitrosoproline (NPRO). The mean NPRO content in urines voided just before administration of nitrate was 4.1 micrograms/L. Mean NPRO levels remained low until 6 h after nitrate intake. Mean NPRO contents in urines voided 6-8 h, 8-10 h, 10-15 h and 15-24 h after nitrate administration were 10, 40, 74 and 53 micrograms/L. respectively. The highest NPRO content found was 320 micrograms/L. These findings demonstrate that intake of one large dose of nitrate leads to enhanced nitrosation in the body, which lasts at least one day. Surprisingly, in urine from 21 patients who had been ingesting 2.5-9 g ammonium nitrate daily for several months to prevent the redevelopment of calcium phosphate renal stones, only slightly enhanced NPRO levels were found: less than 1-32 micrograms/L; mean value, 6.2 micrograms/L. In most of the urines, from the healthy volunteers as well as from the patients, N-nitrosothiazolidine-4-carboxylic acid was also detected. Results from the volunteers indicated that urinary excretion of this compound also increases several hours after intake of one large dose of nitrate.
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Whole blood and urine from 23 patients ingesting ammonium nitrate daily in amounts varying from 2 . 5-9 g were analysed for volatile N-nitrosamines. By contrast with reports in the literature N-nitrosodimethylamine and N-nitrosodiethylamine were not found in blood (limit of detection 0 . 1 micrograms/kg) but a trace of N-nitrosopyrrolidine was found in the blood of one subject. Small amounts of N-nitrosomorpholine in some blood samples and in one blank were believed to be formed during the analysis since morpholine had been added to the samples to indicate artefactual nitrosamine formation. Traces of N-nitrosodimethylamine (0 . 1 microgram/kg) were found in six of the 23 urine samples.
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The GLC/TEA method for N-nitrosodimethylamine (NDMA) in beer was studied collaboratively by 13 laboratories from 7 countries. Collaborators were asked to analyze a total of 10 randomly labeled samples of beer consisting of the following duplicates: a naturally contaminated commercial beer; a beer extremely low (ca 0.1 ppb) in NDMA; and the low NDMA beer spiked with 0.5, 1.9, and 5.0 ppb NDMA. The pooled repeatability and reproducibility coefficients of variation (CV) for all samples were 17% and 27%, respectively. However, when data from 2 laboratories (outliers) were omitted, the corresponding CV values improved considerably (11% and 15%, respectively). Variance analysis showed the presence of a significant laboratory-sample interaction when all data were used for analysis, but this interaction disappeared when data from the 2 outlying laboratories were excluded. The pooled percent recovery of the overall method (omitting outliers) was 101.4 +/- 3.5. All the laboratories detected NDMA in the low NDMA beer. The method was adopted official first action.
Twelve healthy volunteers ingested orally 7-10.5 g of NH4NO3 in a single dose and 12 others received 9.5 g of NaNO3 intravenously in about 60 min. Samples of blood, saliva and urine were collected just before administration of nitrate and at various times afterwards during a 24 h period. Saliva and urine were analysed for volatile NA, nitrate and nitrite. Blood was analysed for nitrate. Neither in urine nor in saliva were NA other than NDMA detected. Of the 188 urine samples, only 13% contained more than 0.1 microgram NDMA/kg, the highest level being 0.5 microgram/kg. In 92% of the 179 saliva samples, less than 0.5 microgram NDMA/1 was found. The saliva of 1 person contained 0.7-8.9 microgram NDMA/1. Nitrate levels in blood rose sharply during the first hour after intravenous nitrate administration and 2 hours after oral intake, reaching peak values of ca. 6 mmol/1. Peak values for NO-3 + NO-2 in saliva, which were reached 2-6 hours after intake, varied strongly between individuals, ranging from 4 to 43 mmol/1. Nitrite was detected in 26% of the urine samples. There was no correlation between NDMA contents and nitrite in urine. An average of 75% of administered nitrate was excreted in urine in 24 h. However, nitrate contents in blood, urine and saliva after 24 h were still higher than before the nitrate intake.
The nickel content of 260 samples from various types of foods available in the Netherlands was measured by means of flameless atomic absorption spectrometry. In most samples the nickel content was found to be less than 0.5 mg/kg. Two products contained considerably more nickel than all the other foodstuffs, viz. nuts and cacao products, in which nickel concentrations up to 5.1 and 9.8 mg/kg, respectively, were measured. Occasionally nickel contents above 1 mg/kg were found in margarine and sauces.
Duplicate portions of 24-hour diets of 110 adults have been analyzed for aluminium, cadmium, copper, lead, manganese, mercury, zinc, nitrate, nitrite and volatile N-nitrosamines. The mean daily intake of copper (1.2 mg) is only about 50% of recommended values; mean daily intakes for manganese (3.3 mg) and zinc (8.4 mg) are adequate and marginal respectively with respect to recommended amounts. For the non-essential elements Al, Cd, Hg and Pb, mean daily intakes of 3.1 mg, 0.01 mg, 0.002 mg and 0.034 mg were found, respectively. For Cd this amounts to 17% of the acceptable daily amount, for Al, Hg and Pb 5%, 5% and 8%, respectively. Since 1976-1978 the dietary intake of lead has been reduced by a factor three; for the other six elements daily dietary intakes are almost the same as in 1976-1978. Average nitrate intake was 52 mg NO3-/day, about 25% of the ADI. Only 16 diets contained a measurable amount of nitrite. The highest daily intake (0.7 mg NO2-) is less than 10% of the ADI. Volatile N-nitrosamines were detectable in two duplicate diets (NDMA and NPIP). It is estimated that the daily dietary intake of volatile N-nitrosamines is around 0.1 microgram or less.