Dioxins, dioxin-like PCBs and non-dioxin-like PCBs in foodstuffs: occurrence and dietary intake in The Netherlands.

Data on occurrence of dioxins (polychlorinated dibenzo-p-dioxins [PCDDs] and dibenzofurans [PCDFs]), dioxin-like PCBs (polychlorinated non-ortho and mono-ortho biphenyls) and non-dioxin-like PCBs (as represented by the so-called indicator-PCBs: congeners 28, 52, 101, 118, 138, 153 and 180) in food products consumed in The Netherlands that were collected in measurement programs carried out during 1998 and 1999, and combined with food consumption data to assess the dietary intake of these persistent food contaminants. The estimated median life-long-averaged intake of the sum of dioxins and dioxin-like PCBs in the population is 1.2 pg WHO-TEQ (toxic equivalents) per kg body weight (bw) per day, while the estimated median life-long-averaged intake of indicator-PCBs is 5.6 ng per kg bw per day. The contribution of different food groups to the total intake of both dioxins + dioxin-like PCBs and non-dioxin-like PCBs is fairly uniformly distributed over the foods consumed: meat products (23% and 27%, respectively), dairy products (27% and 17%, respectively), fish (16% and 26%, respectively), eggs (4% and 5%, respectively), vegetable products (13% and 7%, respectively), and industrial oils and fats (17% and 18%, respectively). Compared with earlier intake estimations the present estimation shows a continued reduction in the intake of dioxins as well as PCBs. This reduction is related to the decrease in the concentration of these substances in the majority of foodstuffs. Nevertheless, a small part of the population still has a rather high life-long averaged intake: 8% of the population is exposed to intake levels above the tolerable weekly intake for dioxins and dioxin-like PCBs of 14 pg WHO-TEQ per kg bw per week, as recently derived by the Scientific Committee on Food of the European Commission. For the non-dioxin-like PCBs an internationally accepted maximum intake level is still lacking. However, to provide risk managers with a health-based guideline to prevent health effects of exposure to non-dioxin-like PCBs, the (international) derivation of a tolerable daily intake is recommended. Monitoring the dietary intake of PCBs is just as important as monitoring the intake of dioxins and dioxin-like PCBs, and attempts to decrease the exposure to both compound classes need continuous attention.

Acrylamide exposure from foods of the Dutch population and an assessment of the consequent risks.

At the end of April 2002, the Swedish Food Administration reported the presence of acrylamide in heat treated food products. Acrylamide has been shown to be toxic and carcinogenic in animals, and has been classified by the WHO/IARC among others as 'probably carcinogenic for humans'. The purposes of this study were firstly to analyse acrylamide contents of the most important foods contributing to such exposure, secondly, to estimate the acrylamide exposure in a representative sample of the Dutch population, and thirdly to estimate the public health risks of this consumption. We analysed the acrylamide content of foods with an LC-MS-MS method. The results were then used to estimate the acrylamide exposure of consumers who participated in the National Food Consumption Survey (NFCS) in 1998 (n=6250). The exposure was estimated using the probabilistic approach for the total Dutch population and several age groups. For 344 food products, acrylamide amounts ranged from <30 to 3100 microg/kg. Foods with the highest mean acrylamide amounts were potato crisps (1249 microg/kg), chips (deep-fried) (351 microg/kg), cocktail snacks (1060 microg/kg), and gingerbread (890 microg/kg). The mean acrylamide exposure of the NFCS participants was 0.48 microg/kg bw/day. Risk of neurotoxicity is negligible. From exposure estimations it appears that the additional cancer risk might not be negligible.

Biomonitoring heavy metals using the barn owl (Tyto alba guttata): sources of variation especially relating to body condition.

The feasibility of using the Barn Owl (Tyto alba guttata) to monitor environmental quality in the Netherlands was investigated, using Cd, Cu, Pb, Mn, and Fe as indicators for environmental contamination. Throughout 1992, bird-watchers, volunteers, and officials submitted 53 birds. The age and geographical distribution of these birds, formed a representative sample of the population. The following interrelationships were investigated: cause of death, nutrient reserve, age, time of death, place of death, body measurements, sex, condition, and heavy metal concentration in kidney, liver, and tibia. Twenty-eight animals had died after collisions. Fifteen Barn Owls died of exhaustion. In total, twenty-four birds were exhausted, with coccidiosis or other parasitic gastrointestinal infections. The condition of the birds showed that as the birds' condition worsened, fat reserves were depleted before protein reserves. Significant linear relationships were found between decreasing protein reserves and decreasing dry weights of the liver, kidney, flight muscle and heart, but not of the tibia. An asymptotic, nonlinear relation was observed between dry organ weight and fat reserve. This suggested that fat reserves were only found when protein reserves exceeded 15% of the body mass at starvation. Concentrations of Cu and Fe in liver and kidney rose as protein reserves fell; the total content of Cu and Fe per organ, however, remained constant. The Mn concentration of these organs remained constant; Mn content increased with increasing organ sizes. Neither Cd nor Pb showed a clear relationship with parameters of body condition. The ratio between the organ content of Pb or Cd and the dry organ weight, however, revealed some birds from contaminated habitats. The findings suggested that concentrations of environmental contaminants should be measured on a dry weight basis. Furthermore, depending on the pharmacokinetic characteristics of a contaminant, the total content of that contaminant per organ can be more informative than the concentration. In this one year sample of Barn Owls, no indications were found of toxic levels of Cd, Cu, Pb, Mn, or Fe in the Netherlands. It is concluded that the Barn Owl is a suitable biomonitor. Furthermore, a network of volunteers can produce an informative sample of the Barn Owl population without interfering with the population.

Effects of feed additives and veterinary drugs on aldosterone production and release by porcine adrenal cells in vitro.

The preparation of suspensions of porcine adrenocortical cells is described. Within the conditions adopted, the cell suspension responded to various agents as expected. It was possible to screen drugs (standard range 0.3-100 microM, incubation period 1 h) for actions on the production/release of aldosterone by the cortical cells using 1 microM deoxycorticosterone as substrate. Progesterone, pregnenolone or corticosterone were also used as substrates. Feed additives of the quinoxaline type induced a slowly developing inhibition of aldosterone production/release by the cell suspension, which was virtually irreversible. During the standard 1 h incubation period inhibitions of up to 22 +/- 2% of control were observed, which increased upon prolongation of the incubation by 2 h. With 100 microM cyadox the inhibition increased from 19 +/- 2% to 35 +/- 2% with prolonged incubation. Ten nitrofuran compounds exerted a more rapidly developing inhibition (by up to 79 +/- 1% of control) of aldosterone production/release, which was reversible. A submaximal inhibition with 10 microM furazolidone of 21 +/- 5% increased to 40 +/- 1% with longer incubation. The concentrations at which these compounds exerted this effect in vitro were well below the peak blood plasma concentrations encountered after administration of the drugs in therapeutic doses. Polyether-antibacterials/ionophores rapidly inhibited aldosterone production/release (to 26 +/- 1% of control) and this effect was completely reversible. The nitroimidazole compounds tested did not affect aldosterone production/release when deoxycorticosterone or progesterone were used as substrates. With use of corticosterone and to a lesser extent with pregnenolone as substrates a clear inhibition (to 73 +/- 3% of control) of aldosterone production was obtained. Amprolium in concentrations up to 100 microM, with deoxycorticosterone as substrate, did not induce a significant change in aldosterone production/release by the suspension of adrenocortical cells. In the same dose range tylosin and roxarsone induced a small but significant inhibition (by up to 10 +/- 3% of control) of aldosterone production/release, which was not dose-dependent. It is concluded that a wide range of growth-promoting drugs may be able to change aldosterone production/release in the animal.

Lead intoxication in cattle: a case report.

During the autumn of 1989 a feed contamination induced a widespread lead intoxication of cattle in the northern provinces of The Netherlands (Groningen and Friesland). Over 300 farms were involved, affecting about 15,500 animals (mostly dairy cattle). For a period of one to four weeks these animals took up a thousand kg of lead. This resulted in lead levels in milk, livers, and kidneys above the regulatory safety limits. Due to the chelating therapy, which was rapidly applied by the local veterinarians, only about 30 animals died of an acute lead intoxication. A joint action of the governmental and private authorities prevented exposure of consumers to lead-contaminated animal products. Based on observations, measurements and literature data, predictions were made of the lead levels to be expected in animal products and the time needed for depletion of these levels. The appropriate animals were ear-tagged to ensure their identification, and the decline in time of the lead levels in milk and offals was conscientiously monitored. In the second week of 1990 the lead concentrations were decreased to levels well below the regulatory limits, and hence the tags were removed. The present paper reports our observations and conclusions, especially regarding treatment, predictions and outcome of this incident.

Increased metallothionein in the liver and kidney of patients with amyotrophic lateral sclerosis.

To evaluate the putative role of metals and trace elements in the pathogenesis of classic amyotrophic lateral sclerosis, we studied the metallothionein levels in liver and kidney samples obtained at autopsy from 24 patients with amyotrophic lateral sclerosis and 18 controls. To assay metallothioneins and copper, cadmium, and zinc bound to metallothioneins, we used high-performance liquid chromatography directly coupled to flame atomic absorption spectrometry. Total cadmium, zinc, and copper concentrations were determined separately with the use of graphite furnace atomic absorption spectrometry with Zeeman background correction. The median liver metallothionein level was 60.3 mg/kg (range, 9 to 318 mg/kg) in the patients with amyotrophic lateral sclerosis and 12.6 mg/kg (range, 0 to 104.5 mg/kg) in the controls. In the kidney, median metallothionein levels were 126.9 mg/kg (range, 44 to 387 mg/kg) in the patients with amyotrophic lateral sclerosis and 64 mg/kg (range, 13.1 to 187 mg/kg) in the controls. Total zinc, cadmium, and copper concentrations, as measured by atomic absorption spectrometry, were not significantly different in patients vs controls. Our finding of elevated metallothionein levels in organs from patients with amyotrophic lateral sclerosis may indicate an increased exposure to metals.

[Lead poisoning in cattle in Northern Netherlands. Follow-up study of 2 farms]. / Loodintoxicatie bij rundvee in Noord-Nederland. Vervolgonderzoek bij twee bedrijven.

The after-effects of a serious lead intoxication were studied. This intoxication was caused by contaminated feed. Calves and cows of two dairy farms were examined up to half a year after the incident with the contaminated feed in October 1989. Clinical signs were observed and blood samples were taken. Blood parameters like zinc-protoporphyrin (ZPP), haemoglobin, RBC, WBC, MCV, haematocrit, MCHC, and the blood lead levels were analysed. Cattle of one of the most afflicted farms showed severe effects of lead intoxication: blindness, muscle twitching and hyperirritability. Two animals died. Forty percent of the affected cows had to be slaughtered. The ZPP levels in calves of this farm were still elevated after six months. The zinc-protoporphyrin level in blood seemed to coincide better with the clinical signs than the blood lead level. Animals with less than 3 mg ZPP/l RBC showed no irreversible effects of the lead intoxication. It is suggested that ZPP could be a useful predictor for the after-effects of lead intoxication.

[Lead poisoning in cattle in north Netherlands. October 1989-January 1990]. / Loodintoxicatie bij rundvee in Noord-Nederland. Oktober 1989-januari 1990.

By the end of 1989 a serious lead intoxication of cattle occurred in the northern part of the Netherlands (provinces Groningen and Friesland). This intoxication appeared to be caused by contaminated feed. Over 300 farms were stricken, with about 15,500 animals (mostly dairy cattle). In a period of one to four weeks these animals consumed about 1,000 kg of lead. This resulted in lead levels in milk, livers, and kidneys above the regulatory safety limits. Thanks to the chelating therapy that was rapidly applied by the local veterinarians, only about 30 animals died of an acute lead intoxication. The cooperating governmental and private authorities took action to prevent exposure of consumers to lead-contaminated animal products. Based on careful estimations, predictions were made of the lead levels to be expected in animals products and the time needed for depletion of these levels. The appropriate animals were marked to ensure their identification, and the decline in time of the lead levels in milk and offals was conscientiously monitored. In the second week of 1990 the lead concentrations were decreased to levels well below the regulatory limits, and hence the marks were removed from the animals.

[Abuse of pesticides: effects on farm animals and birds]. / Verkeerd gebruik van bestrijdingsmiddelen: effecten op landbouwhuisdieren en vogels.

Pesticides are unique toxic compounds, as they have to comply with two requirements: A high degree of toxicity as well as being highly specific. These requirements are difficult to combine. In the past, risk assessment was limited to the danger to human health, but today ecological risks are also taken into account. Consequently, modern pesticides would seem to be relatively safe. However, research in this particular field is scarce. Injurious effects on domestic animals due to pesticides is almost always caused by abuse or accidents, having their origin in human failure. Injury to birds (the only species thoroughly monitored) is also rarely attributable to any type of side-effect of legal pesticide usage. However, cases of deliberate misuse or abuse, intended to kill birds, are very common.

Comparative study of the effect of the effect of carbadox, olaquindox and cyadox on aldosterone, sodium and potassium plasma levels in weaned pigs.

To study the effects of olaquindox and cyadox on aldosterone, sodium and potassium in the blood in comparison with the effects of carbadox, weaned pigs were fed these compounds in different doses. Pigs treated with 100 and 200 ppm carbadox showed a significant decline of aldosterone after five and three weeks, respectively, compared with control values. In the 200 ppm group treatment was interrupted at week 4. With olaquindox a continuous, significant decline was found from 50 ppm and above after five weeks, and from 25 ppm and above (but excluding the 100 ppm group), after six weeks. In the cyadox groups a significant decline was measured after six weeks in the 50, 200 and 400 ppm groups. Only the 200 ppm group had an earlier response at three and five weeks. A decrease of sodium to hyponatraemic levels in the carbadox groups was seen after three weeks in the 200, and after five weeks in the 100 ppm group. In the olaquindox groups only the 200 ppm dosage showed a consistent decrease to hyponatraemic levels from four weeks treatment. In the cyadox groups the 200 ppm dosage reached a hyponatraemic level after six weeks. An increase of potassium to hyperkalaemic levels occurred at 100 and 200 ppm carbadox dosage after four and three weeks, respectively, and at 200 ppm olaquindox dosage after four weeks. No hyperkalaemic levels were seen in the cyadox groups. It is concluded that the toxic effect of olaquindox, despite minor differences, is comparable with that of carbadox but that cyadox is less toxic.

Persistence of carbadox-induced adrenal lesions in pigs following drug withdrawal and recovery of aldosterone plasma concentrations.

This study was performed to investigate the persistence of carbadox-induced adrenal lesions in pigs after withdrawal of the drug. Six groups (N = 13) received 0 (control group), 25, 50, 100 and 200 ppm carbadox. After 10 weeks, carbadox was withdrawn from the feed. Five and 11 weeks after withdrawal, two pigs per group were necropsied and the adrenals were examined histologically. Five weeks after withdrawal, recovery of lesions was seen in the 25 and 50 ppm groups. In the 100 and 150 ppm groups, adrenal changes were still present. After 11 weeks an incomplete recovery occurred in the 100 ppm group and in one of the pigs from the 150 ppm group; the second pig of this group still demonstrated moderate changes. Pigs from the 200 ppm group showed severe changes and absence of a clear zonal differentiation. Plasma aldosterone values started to recover 2 weeks after withdrawal of carbadox. Histological examination suggested stimulation of the aldosterone-producing glomerular zone, eventually resulting in regressive changes. The mechanisms that possibly induced this continuous stimulation are discussed.

[A case of common salt poisoning in slaughtering pigs]. / Een geval van keukenzoutintoxicatie bij mestvarkens.

Poisoning with common salt is one of the most frequent forms of poisoning in finishing pigs. As a rule, this is due to too much salt in the feed, in combination with a limited supply of drinking water. When a diagnosis of common salt poisoning is established, the animals will have to be rehydrated by degrees. Animals showing clinical symptoms have a bad prognosis. A case of sodium chloride poisoning is reported in the following paper.

Isolation and quantitation of cadmium-, zinc- and copper-metallothioneins by high-performance liquid chromatography-atomic absorption spectrometry.

Metallothioneins (MTs) were separated and quantitated by reversed-phase high-performance liquid chromatography (RP-HPLC), in direct combination with atomic absorption spectrometry (AAS) for quantitation of the metal contents in MTs. MTs were eluted from an RP-8 column with a gradient of Tris buffer pH 7.0 and methanol, and were detected by UV absorbance (220 nm). Commercially available purified MTs from horse kidney and rabbit liver were analyzed for purity and metal composition. One lot of horse kidney yielded only 50% of the estimated value. In some cases, the certified metal content differed considerably from the values found. The method was also tested with rat liver and fetal bovine liver. The metal contents found in MTs by use of graphite-furnace atomic absorption spectrometry corresponded well with the values found by RP-HPLC-AAS. Molar ratios of cadmium, zinc and copper were calculated in MT-1, MT-2 and total MT.

[A case of selenium poisoning in piglets]. / Een geval van seleniumvergiftiging bij biggen.

Acute paralysis was observed in suckling piglets and weaner piglets on a pig breeding farm. Pathomorphological investigations revealed characteristic lesions in the central nervous system. These lesions were indicative of selenium poisoning. This was verified by chemical-toxicological analysis of organs and tissues of the affected pigs. Poisoning was shown to have been caused by the feed: one feed preparation contained an extremely large amount of selenium, which was due to human failure.

Environmental contamination by heavy metals and fluoride in the Saeftinge salt marsh (The Netherlands) and its effect on sheep.

The Saeftinge salt marsh in the Westerschelde estuary (southwestern part of the Netherlands) represents one of the very few tidal brackish marsh ecosystems in Western Europe. From May 1983 to May 1985 the local pollution of this marsh with metals and fluoride was investigated. Samples from soil and vegetation were analysed monthly for cadmium, lead, copper, zinc, manganese, iron, and fluoride. The amount of these substances in the soil appeared to be related to both the percentage of clay particles and organic matter in the soil and to the frequency of tidal submergences. In vegetation, the pollutants clearly showed a seasonal variation. Adherent clay, deposited on the plants during submergences, contributed considerably to the total amount of these elements. Sheep grazing in the marsh were investigated for renal and faecal excretion of these elements, but no relation between these samples and the seasonal variation in vegetation was found. Presumably sheep consumed vegetation selectively, avoiding the more contaminated plants. Regular clinical inspections of the sheep revealed no signs of acute or chronic intoxication. The organs of sheep that died during the investigation showed increased levels of cadmium in the liver and kidney, and iron in the liver, but not enough to cause alarm. Fluoride found in the rib material, although slightly increased, did not indicate fluorosis. In conclusion, contamination with metals and fluoride, as observed in the salt marsh, apparently does not impair the health of locally grazing sheep. This may be due to selective consumption behaviour of the sheep, their stabling during the winter, limited biological availability of the elements studied, and a sheep management adapted to the local circumstances.

Some pharmacokinetic observations of carbadox medication in pigs.

Concentrations of carbadox and a first metabolite, desoxycarbadox, were measured in contents of the porcine gastrointestinal tract after in-feed administration of carbadox in therapeutic dosages (100-150 ppm). The levels of carbadox in the relevant parts of the gastrointestinal tract were found to be lower than the MIC-values reported for enteropathogenic microorganisms at their sites of action. The presented observations do not provide a pharmacological rationale for the therapeutic use of carbadox in the treatment of dysentery and diarrhoea in swine. The carbadox levels encountered in the proximal part of the gut (stomach, duodenum) however, seem to indicate that in-feed administration of 50 ppm carbadox can provide an effective prophylaxis against Treponema hyodysenteriae, a causative agent in swine dysentery. The timecourse of the blood levels of carbadox and desoxycarbadox after in-feed administration of carbadox (50 ppm) and the concentration profiles in the gastrointestinal tract are discussed with regard to the disposition of this drug in pigs.