Food Additives & Contaminants
ISSN: 0265-203X (Print) (Online) Journal homepage: http://www.tandfonline.com/loi/tfac19
Lead intoxication in cattle: A case report A. J. Baars , H. Van Beek , I. J. R. Visser , G. Vos , W. Van Delft , G. Fennema , G. W. Lieben , K. Lautenbag , J. H. M. Nieuwenhijs , P. A. De Lezenne Coulander , F. H. Pluimers , G. Van De Haar , T.J. Jorna , L. G. M. Th. Tuinstra , P. Zandstra & B. Bruins Jzn To cite this article: A. J. Baars , H. Van Beek , I. J. R. Visser , G. Vos , W. Van Delft , G. Fennema , G. W. Lieben , K. Lautenbag , J. H. M. Nieuwenhijs , P. A. De Lezenne Coulander , F. H. Pluimers , G. Van De Haar , T.J. Jorna , L. G. M. Th. Tuinstra , P. Zandstra & B. Bruins Jzn (1992) Lead intoxication in cattle: A case report, Food Additives & Contaminants, 9:4, 357-364, DOI: 10.1080/02652039209374082 To link to this article: http://dx.doi.org/10.1080/02652039209374082
Published online: 10 Jan 2009.
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FOOD ADDITIVES AND CONTAMINANTS, 1992, VOL. 9, NO. 4, 3 5 7 - 3 6 4
Lead intoxication in cattle: a case report
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A. J. BAARS†, ‡‡‡ H. VAN BEEK†, I. J. R. VISSER ‡, G. VOS§, W. VAN DELFT¶ G. FENNEMA||, G. W. LIEBEN‡, K. LAUTENBAG††, J. H. M. NIEUWENHUUS‡‡, P. A. DE LEZENNE COULANDER§§, F. H. PLUIMERS¶¶, G. VAN DE HAAR||||, TJ. JORNA‡,§§§ L. G. M. TH. TUINSTRA¶, P. ZANDSTRA‡ and B. BRUINS JZN††† †DLO-Central Veterinary Institute, Lelystad; ‡ Animal Health Service in NorthNetherlands, Drachten; § Ministry of Agriculture, Nature Management and Fisheries, Dept for the Environment, Quality & Nutrition, 's-Gravenhage; ¶ DLO-State Institute for Quality Control of Agricultural Products, Wageningen; || Ministry of Agriculture, Nature Management and Fisheries, Veterinary Service, 's-Gravenhage; †† Ministry of Agriculture, Nature Management and Fisheries, General Inspectorate, Division East, Zwolle; †† Ministry of Welfare, Public Health and Cultural Affairs, Central Veterinary Public Health Chief Inspectorate, Rijswijk; §§ Ministry of Welfare, Public Health and Cultural Affairs, Regional Public Health Inspectorate, Leeuwarden; ¶¶ State Service for Cattle and Meat Inspection, 's-Gravenhage; || || Ministry of Welfare, Public Health and Cultural Affairs, Central Public Health Inspectorate, Rijswijk; ††† Ministry of Welfare, Public Health and Cultural Affairs, Regional Veterinary Inspectorate, Groningen; The Netherlands (Received 16 February 1992; accepted 3 June 1992) 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. Keywords: cattle, feed, lead, liver, kidney
Abbreviations AID CDI-DLO EDTA GDNN
General Inspectorate, MLNV DLO-Central Veterinary Institute Ethylenediaminetetraacetate (Na-Ca salt) Animal Health Service in North-Netherlands
‡‡‡ Please address correspondence to A. J. Baars, at: RIKILT-DLO, PO Box 230, NL-6700 AE Wageningen, The Netherlands. §§§ Present address: Royal Netherlands Veterinary Association, Utrecht, The Netherlands. 0265-203X/92 $3.00 © 1992 Taylor & Francis Ltd.
358
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IGB MLNV MWVC PVV RIKILT-DLO RVV SEM
A. J. Baars et al. Public Health Inspectorate at Leeuwarden Ministry of Agriculture, Nature Management and Fisheries Ministry of Welfare, Public Health and Cultural Affairs Cattle and Meat Board DLO-State Institute for Quality Control of Agricultural Products State Service for Cattle and Meat Inspection Standard error of the mean
Introduction During October 1989, seemingly unrelated health problems were observed at several dairy farms in the provinces Groningen and Friesland. The symptoms observed in a number of animals were: bad appetite, slowness, nervous ear twitching. Other animals showed nervous symptoms such as pushing, gnashing of teeth, and refusing to lie down. Based on differential diagnosis, lead poisoning seemed a possible cause. This suspicion was confirmed by blood analysis, showing high lead levels. Affected animals were treated with EDTA and, wherever possible, given a hay ration. The source of the intoxication remained unclear, until the veterinary practice at Winsum (Groningen) was consulted about a calf with nervous symptoms. This animal was fed with milk, hay, and concentrate. The concentrate was sent to the GDNN for lead analysis. On 27 October an extremely high lead amount was established in this concentrate: 1280 mg per kg. The concentrate contained protopec as one of its components, and this contained 5159 mg lead per kg dry matter. This identified the cause of the intoxication. The relevant authorities were alerted, and the MLNV started to coordinate the necessary measures. Soon the incident appeared to be very extensive: some 330 farms, counting about 15 500 animals in total, were involved. The IGB, in cooperation with the dairy factories, analysed milk samples from the farms involved. The levels found were well above the limit for lead in milk (0-05 mg per kg [Nederlandse Staatscourant 1985, 1988]) as regulated in the Food and Drugs Act (Rijkskeuringsdienst van Waren 1989). The lead contamination of the feed was confirmed on 1 November by the RIKILT-DLO. The lead levels found in feed are summarized in table 1. The contaminated feed had been delivered since the beginning of October. It showed an inhomogeneous and lumpy structure, sometimes with brownish discolouration, which appeared to be caused by the contaminating substances. With the source, the extent and the severity of the intoxication known, several measures had to be implemented with due haste. The feed mill recalled the feed. This operation was controlled by the AID, and completed in the first week of November. Milk unsuited for consumption was collected separately and processed into powder to facilitate storage. Later on, the lead content of this milk powder was found to permit its usage as cattle feed (Rijkskeuringsdienst van Waren 1989). Investigations of the AID revealed that the contamination originated from a batch of rice bran. This batch constituted an element of the protopec used in the feed mill, and was heavily contaminated with lead and zinc, while arsenic, cadmium, copper, and mercury also were present (see table 1). The case is now before court.
Lead intoxication in cattle
359
Table 1. Observed and permitted amounts of metals in cattle feed (in mg per kg feed). Metal
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Lead Arsenic Cadmium Zinc Copper Mercury
Observed amount (range)a
Permitted amount1"
300-2300 10-35
5 2 1 250 35C 0-1
0-5
100-900 0-200 0-0-35
Since identical components were used to prepare different kinds of cattle feed, considerable differences in metal amounts were seen. The levels presented here illustrate some representative batches of feed for dairy cattle. a Analytical data: DLO-State Institute for Quality Control of Agricultural Products (RIKILT-DLO), and General Inspectorate of the Ministry of Food, Nature Management and Fisheries (AID). b Cattle Feed Regulations 1986 and 1988. c For calves 50mg/kg is permitted.
Toxicology From the viewpoint of animal health (lead toxicity) as well as from the viewpoint of public health (lead levels in animal products above residue limits) the current intoxication was an extremely serious one. From the data collected by the AID (the difference between the amounts of feed delivered and recalled), an estimated thousand tons of lead-contaminated feed was actually consumed by the animals. These animals consumed about 1000 kg lead, over a period of one to four weeks. Naturally, enormous variations occurred between the various farms: based on the data obtained, the actual uptake varied between 1 and 370 g of lead per animal (averaged per farm). The mean uptake for all farms involved was 65 g of lead per animal. This amount, if administered in one (oral) dose, is lethal: the acute lethal dose for an adult cow is 6-60 g (Hapke 1988, Humphreys 1988). Heavy metals administered during a period of time are accumulated in the organs involved in their excretion: liver and kidney (Hoskam 1958, Sharma et al. 1982, Cheville 1988, Hapke 1988, Humphreys 1988). Furthermore, increased uptake will produce increased levels in milk and meat (Sharma et al. 1982, Hapke 1988, Humphreys 1988). Hence all bovine products from the farms involved had to be controlled scrupulously regarding the public health aspects. Marking of cattle In consultation with the MLNV, the MWVC, and the PVV, it was decided on 1 November that marking of the affected animals was necessary in order to be able to trace and identify them. Based on the observed levels of lead in feed and milk, lead levels well above the regulatory limits in liver and kidney (Nederlandse Staatscourant 1985, 1988) were expected, which prohibited consumption of these products. Also meat lead levels above that limit seemed likely. These limits are set by the Food and Drugs Act, and are presented in table 2. Criteria for the marking of animals were drafted by the CDI-DLO and the MLNV on 2 November. The starting point was the consideration that the use of
360
A. J. Baars et al. Table 2. Regulatory limits (Food and Drugs Act) for heavy metals in bovine products (in mg per kg fresh weight).
Lead Cadmium Mercury Arsenica
Milk
Meat
Liver
Kidney
0-05 0-005 0-01
0-4
0-05 0-05
1-0 1-0
0-05
0-1
0-5
1-5 3-0 0-1 0-5
—
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a Action limits (the Food and Drugs Act does not regulate arsenic limits).
contaminated feed was terminated on 30 October at the latest. The risk of lead levels above the limits in meat and/or organs from animals of a particular farm was considered negligible if the feed used on that farm had contained less than 10 mg lead per kg, and milk samples from that farm after 31 October showed lead concentrations of less than 0 • 025 mg per kg milk (or alternatively, if concentrations were less than 0-05 mg per kg milk in two consecutive samples taken on different days after 1 November). In that case marking of animals on that farm was considered unnecessary. Marking was deemed necessary if these criteria were not met. The PVV tagged over 15 000 animals (about 300 farms) along these lines in week 45 (4th-10th November, 1989). Almost identical criteria were applied regarding the milk. Milk from farms sampled in week 45 or thereafter was released for human consumption if it contained less than 0-026 mg lead per kg milk, or less than 0-051 mg per kg milk in two consecutive samples (Rijkskeuringsdienst van Waren 1989).
Predictions
The results of experiments by Vreman et al. (1986) were used to predict the lead levels in the animal products surviving the intoxication. These authors studied the carry-over of some heavy metals in dairy cattle; their findings, and the carryover factors calculated from their data are presented in table 3. The uncertainty of these carry-over factors, however, needs to be stressed: Vreman et al. (1986) administered a dose of 0-2 g lead per animal per day during several months, while cattle affected by the current intoxication consumed roughly 9 g lead per animal per day during one to four weeks (table 3). The carry-over factors calculated from Vreman et al. (1986), applied to the current intoxication, resulted in expected lead levels which are also presented in table 3. Obviously, lead levels well above the regulatory limits seemed very likely. Once the uptake of lead is terminated, the biological half-life of lead determines its decrease in animal organs (including milk). Reported values (Sharma et al. 1982, Tsuchiya 1986, Humphreys 1988) for this parameter vary from 18 days to 2 months. Hence, based on a worst case approximation it seemed possible that the cattle markings needed to be maintained for a period up to one year. On the basis of the levels of the other contaminating metals in the feed, problems were to be expected for cadmium only. Levels above regulatory limits for the other metals seemed very unlikely.
Lead intoxication in cattle
361
Table 3. Literature data, lead levels to feed and bovine products as per 1 November 1989, calculated carry-over factors, and predicted product levels. Product levels:*
Feed
Milk
Meat
Liver
Kidney
2-5 10 100-450
0-005 0-011 0-200
0-03 0-04 —
0-16 0-52 —
0-46 1-05 —
Milk
Meat
Liver
Kidney
Control Experiment1"
0-002 0-001
0-012 0-004
0-064 0-052
0-184 0-105
Predicted product levels:"
Milk
Meat
Liver
Kidney
Control15 Experiment1' Incident0 Carry-over factors:1* b
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At 100 mg lead per kg feed At 450 mg lead per kg feed
e
0-10 0-45'
0-4 1-8"
e
5 23 c
10e 45 e
a
mg lead per kg fresh weight. •"Control' and 'Experiment' are from Vreman et al. (1986) (see text). c 'Incident' represents the current intoxication as caused by lead-contaminated feed. d The carry-over factor is defined as 'lead level in bovine product' divided by 'lead level in feed'. 'Above regulatory limits (table2). Starting point for calculations is a feed uptake of 20 kg (dry material) per animal per day. On the basis of a mean uptake of 65 g lead per animal during a period of intoxication of one to four weeks (see text), the theoretial lead level in feed must have been 450 mg/kg for a feeding period of one week, and 100 mg/kg for a feeding period of one month.
Results Lead in meat and offals of cattle slaughtered in the period during which this cattle was marked, was measured by the RIKILT-DLO. Indeed levels well above the regulatory limits for liver and kidney were established. Only in meat were the levels measured below the regulatory limit. Significant concentrations of cadmium were not found, and it could be concluded that levels above the cadmium limits did not occur. Milk lead levels were continuously monitored, and revealed a rapid decrease as illustrated in figure 1. Already in week 45 the mean concentration was below the regulatory limit. Blood samples taken in weeks 49 and 50 allowed a first approximation of the kinetics of lead in the affected animals. Assuming a first-order elimination process, a biological half-time of 10-5 days was derived, with an SEM of 1-1 days. Hence a half-life for lead of 23 days should apply to 99% of the animals involved. The scarce data of offals available by that time were generally in agreement with the estimation. Also Tsuchiya (1986) reported no difference between the half-life of lead in blood and in soft tissues. Therefore the cattle-marking was terminated around 10 January 1990. About ten farms, however, were excepted from this. In their cattle very high amounts of lead were observed, indicating a risk that even on 10 January the levels in offals would be above the regulatory limits. Ongoing analyses carried out with blood and organ samples from these animals warranted their release by the end of January.
362
A.
J. Baars et al.
Lead in milk Average concentration per day 0.14 0.12
^ °- 10 I 1 0.08
£
0.06 0.04 0.02 0
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Day Figure 1. The decline of the mean lead level in milk (in mgPb per litre) during the first weeks of the incident. The regulatory limit is represented by a dashed line. Data: Regional Public Health Inspectorate at Leeuwarden (IGB), and the Association of Cooperating Dairy Factories, Friesland (Leeuwarden).
Lead in livers and kidneys Average content per week Liver
46 47 48 49 50 51 52
44
45
46
47
48
49 50 Week
51
52
1
2
1
Figure 2. The decline of the mean lead levels in livers and kidneys (in mg per kg dry material) during the incident (week 44—1989 to week 2—1990). On this dry-weight basis, levels of 3-5 mgPb per kg dry liver, and 7-0 mgPb per kg dry kidney can be taken as the regulatory limits. Number of samples Week no.
Farms Livers Kidneys
44
45
46
47
48
49
50
51
52
01
02
19 22 27
18 11 21
17 12 22
18 25 22
14 23 25
27 48 48
26 40 40
19 33 33
15 20 20
13 21 21
6 7 7
Data: State Service for Cattle and Meat Inspection (RVV), DLO-State Institute for Quality Control of Agricultural Products (RIKILT-DLO), and Animal Health Service in North-Netherlands (GDNN).
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Lead intoxication in cattle
363
Evaluation The mean amounts of lead in livers and kidneys of intoxicated cattle are presented in figure 2. Clearly the levels decreased sharply during the period from week 44 to week 48. It should be noted, however, that the data of week 44 originate from animals that died of acute lead intoxication. In the weeks following the data refer to animals alive at the time of slaughter. If (also) live animals had been analysed in week 44, the mean levels in that week would probably have been somewhat lower. The levels observed in weeks 44 and 45 are generally in agreement with the expectations summarized in table 3. Only the levels in meat (data not given) appeared to be lower than expected. Apparently the carry-over to meat is reduced if the uptake is high. From the data in figure 1 it is possible to derive a half-life for lead in milk of 4-6 days. This is about 15% longer than the half-life estimated by the IGB (Rijkskeuringsdienst van Waren 1989), who used a smaller but better denned set of data. Likewise, figure 2 allows the deduction of a half-life of 7*4 days for lead in offals. The mean lead blood levels as measured in weeks 44 and 45 are illustrated in figure 3, and show a clear dose-response relation. The time course of lead levels
Lead in blood Average content in weeks 44 and 45 0,40
0,30
£
0,20
0,10 -
0-100
100-500
500-1000
1000-1500
>1500
Content in feed (mg/kg) Figure 3. Mean lead levels in blood (in mg Pb per litre) of cattle during weeks 44 and 45 (1989), related to the different feed levels. Feed level (mg/kg)
Farms Samples
0-100
100-500
500-1000
1000-1500
>1500
17 69
7 31
42 358
60 509
24 160
Data: Animal Health Service in North-Netherlands (GDNN), and DLO-Central Veterinary Institute (CDI-DLO).
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A. J. Baars et al.
in blood beyond week 45 cannot be established reliably, because in later weeks only a limited number of blood samples were analysed. The levels measured in weeks 1 and 2 (1990), however, were all well below 0-1 mg per 1, indicating the return to a normal state of health of the animals involved. Beyond doubt, the EDTA-therapy (Merck-AUV 1989), immediately applied, significantly reduced the number of casualties. Only about 30 animals died as a direct result of the lead intoxication, while some 40 animals had to be slaughtered. The exposure data suggest that a far higher mortality would have occurred if adequate treatment had not been applied so rapidly. Following the incident, veterinary inspections were carried out on a number of farms where high lead levels were observed in blood and/or offals during the incident. No morbid symptoms were observed, and no other consequences of a lead intoxication, such as low birth-weights, early births, or abortions, were seen either. Thanks to the immediate action of the veterinarians in the two northern provinces and the close cooperation of all authorities involved, the damage for the individual farms was limited as far as possible. Export interests were also protected. The risk for the human consumer was smaller than feared at first, and hence the measure to tag the animals could soon be terminated. References CHEVILLE, N. F., 1988, Introduction to Veterinary Pathology (Ames: Iowa State University Press), p. 449. HAPKE, H. J., 1988, Blei. Toxikologie für Veterinärmediziner, 2nd edn (Stuttgart: Ferdinand Enke Verlag), pp. 191-196. HOSKAM, E. G., 1958, Vergiftiging in de praktijk—lood (Intoxications in thefield—lead).Tijdschrift voor Diergeneeskunde, 83, 413-423. HUMPHREYS, D. J., 1988, Lead. Veterinary Toxicology, 3rd edn (London: Ballière Tindall), pp. 49-58. MERCK-AUV, 1989, Dierenartsen behandelen loodvergiftigde koeien (Veterinarians are treating leadintoxicated cows). Merck Reagentia, 2, 41-42. Nederlandse Staatscourant, 1985, 1988, Regeling normen zware metalen (Dutch Governmental Newspaper, 1985, 1988, Regulatory limits for heavy metals), No. 58, 22 March 1985; No. 121, 27 June 1988. RIJKSKEURINGSDIENST VAN WAREN TE LEEUWARDEN, 1989, De besmetting van veevoer met lood in
oktober/november 1989 (Regional Public Health Inspectorate at Leeuwarden, 1989, The leadcontamination of cattle feed in October/November 1989). Annual Report 1989, pp. 19-25. SHARMA, R. P., STREET, J. C., SHUPE, J. L., and BOURCIER, D. R., 1982, Accumulation and depletion
of cadmium and lead in tissues and milk of lactating cows fed small amounts of these metals. Journal of Dairy Science, 65, 972-979. TSUCHIYA, K., 1986, Lead. Handbook on the Toxicology of Metals, 2nd edn, edited by L. Friberg, G. F. Nordberg and V. B. Vouk (Amsterdam: Elsevier), Vol. II, pp. 298-353. VREMAN, K., VAN DER VEEN, N. G., VAN DER MOLEN, E. J., and DE RUIG, W. G., 1986, Transfer of
cadmium, lead, mercury, and arsenic from feed into milk and various tissues of dairy cows—chemical and pathological data. Netherlands Journal of Agricultural Sciences, 34, 129-144.
ISSN: 0265-203X (Print) (Online) Journal homepage: http://www.tandfonline.com/loi/tfac19
Lead intoxication in cattle: A case report A. J. Baars , H. Van Beek , I. J. R. Visser , G. Vos , W. Van Delft , G. Fennema , G. W. Lieben , K. Lautenbag , J. H. M. Nieuwenhijs , P. A. De Lezenne Coulander , F. H. Pluimers , G. Van De Haar , T.J. Jorna , L. G. M. Th. Tuinstra , P. Zandstra & B. Bruins Jzn To cite this article: A. J. Baars , H. Van Beek , I. J. R. Visser , G. Vos , W. Van Delft , G. Fennema , G. W. Lieben , K. Lautenbag , J. H. M. Nieuwenhijs , P. A. De Lezenne Coulander , F. H. Pluimers , G. Van De Haar , T.J. Jorna , L. G. M. Th. Tuinstra , P. Zandstra & B. Bruins Jzn (1992) Lead intoxication in cattle: A case report, Food Additives & Contaminants, 9:4, 357-364, DOI: 10.1080/02652039209374082 To link to this article: http://dx.doi.org/10.1080/02652039209374082
Published online: 10 Jan 2009.
Submit your article to this journal
Article views: 9
View related articles
Citing articles: 2 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=tfac20 Download by: [Universite Laval]
Date: 05 November 2015, At: 20:02
FOOD ADDITIVES AND CONTAMINANTS, 1992, VOL. 9, NO. 4, 3 5 7 - 3 6 4
Lead intoxication in cattle: a case report
Downloaded by [Universite Laval] at 20:02 05 November 2015
A. J. BAARS†, ‡‡‡ H. VAN BEEK†, I. J. R. VISSER ‡, G. VOS§, W. VAN DELFT¶ G. FENNEMA||, G. W. LIEBEN‡, K. LAUTENBAG††, J. H. M. NIEUWENHUUS‡‡, P. A. DE LEZENNE COULANDER§§, F. H. PLUIMERS¶¶, G. VAN DE HAAR||||, TJ. JORNA‡,§§§ L. G. M. TH. TUINSTRA¶, P. ZANDSTRA‡ and B. BRUINS JZN††† †DLO-Central Veterinary Institute, Lelystad; ‡ Animal Health Service in NorthNetherlands, Drachten; § Ministry of Agriculture, Nature Management and Fisheries, Dept for the Environment, Quality & Nutrition, 's-Gravenhage; ¶ DLO-State Institute for Quality Control of Agricultural Products, Wageningen; || Ministry of Agriculture, Nature Management and Fisheries, Veterinary Service, 's-Gravenhage; †† Ministry of Agriculture, Nature Management and Fisheries, General Inspectorate, Division East, Zwolle; †† Ministry of Welfare, Public Health and Cultural Affairs, Central Veterinary Public Health Chief Inspectorate, Rijswijk; §§ Ministry of Welfare, Public Health and Cultural Affairs, Regional Public Health Inspectorate, Leeuwarden; ¶¶ State Service for Cattle and Meat Inspection, 's-Gravenhage; || || Ministry of Welfare, Public Health and Cultural Affairs, Central Public Health Inspectorate, Rijswijk; ††† Ministry of Welfare, Public Health and Cultural Affairs, Regional Veterinary Inspectorate, Groningen; The Netherlands (Received 16 February 1992; accepted 3 June 1992) 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. Keywords: cattle, feed, lead, liver, kidney
Abbreviations AID CDI-DLO EDTA GDNN
General Inspectorate, MLNV DLO-Central Veterinary Institute Ethylenediaminetetraacetate (Na-Ca salt) Animal Health Service in North-Netherlands
‡‡‡ Please address correspondence to A. J. Baars, at: RIKILT-DLO, PO Box 230, NL-6700 AE Wageningen, The Netherlands. §§§ Present address: Royal Netherlands Veterinary Association, Utrecht, The Netherlands. 0265-203X/92 $3.00 © 1992 Taylor & Francis Ltd.
358
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IGB MLNV MWVC PVV RIKILT-DLO RVV SEM
A. J. Baars et al. Public Health Inspectorate at Leeuwarden Ministry of Agriculture, Nature Management and Fisheries Ministry of Welfare, Public Health and Cultural Affairs Cattle and Meat Board DLO-State Institute for Quality Control of Agricultural Products State Service for Cattle and Meat Inspection Standard error of the mean
Introduction During October 1989, seemingly unrelated health problems were observed at several dairy farms in the provinces Groningen and Friesland. The symptoms observed in a number of animals were: bad appetite, slowness, nervous ear twitching. Other animals showed nervous symptoms such as pushing, gnashing of teeth, and refusing to lie down. Based on differential diagnosis, lead poisoning seemed a possible cause. This suspicion was confirmed by blood analysis, showing high lead levels. Affected animals were treated with EDTA and, wherever possible, given a hay ration. The source of the intoxication remained unclear, until the veterinary practice at Winsum (Groningen) was consulted about a calf with nervous symptoms. This animal was fed with milk, hay, and concentrate. The concentrate was sent to the GDNN for lead analysis. On 27 October an extremely high lead amount was established in this concentrate: 1280 mg per kg. The concentrate contained protopec as one of its components, and this contained 5159 mg lead per kg dry matter. This identified the cause of the intoxication. The relevant authorities were alerted, and the MLNV started to coordinate the necessary measures. Soon the incident appeared to be very extensive: some 330 farms, counting about 15 500 animals in total, were involved. The IGB, in cooperation with the dairy factories, analysed milk samples from the farms involved. The levels found were well above the limit for lead in milk (0-05 mg per kg [Nederlandse Staatscourant 1985, 1988]) as regulated in the Food and Drugs Act (Rijkskeuringsdienst van Waren 1989). The lead contamination of the feed was confirmed on 1 November by the RIKILT-DLO. The lead levels found in feed are summarized in table 1. The contaminated feed had been delivered since the beginning of October. It showed an inhomogeneous and lumpy structure, sometimes with brownish discolouration, which appeared to be caused by the contaminating substances. With the source, the extent and the severity of the intoxication known, several measures had to be implemented with due haste. The feed mill recalled the feed. This operation was controlled by the AID, and completed in the first week of November. Milk unsuited for consumption was collected separately and processed into powder to facilitate storage. Later on, the lead content of this milk powder was found to permit its usage as cattle feed (Rijkskeuringsdienst van Waren 1989). Investigations of the AID revealed that the contamination originated from a batch of rice bran. This batch constituted an element of the protopec used in the feed mill, and was heavily contaminated with lead and zinc, while arsenic, cadmium, copper, and mercury also were present (see table 1). The case is now before court.
Lead intoxication in cattle
359
Table 1. Observed and permitted amounts of metals in cattle feed (in mg per kg feed). Metal
Downloaded by [Universite Laval] at 20:02 05 November 2015
Lead Arsenic Cadmium Zinc Copper Mercury
Observed amount (range)a
Permitted amount1"
300-2300 10-35
5 2 1 250 35C 0-1
0-5
100-900 0-200 0-0-35
Since identical components were used to prepare different kinds of cattle feed, considerable differences in metal amounts were seen. The levels presented here illustrate some representative batches of feed for dairy cattle. a Analytical data: DLO-State Institute for Quality Control of Agricultural Products (RIKILT-DLO), and General Inspectorate of the Ministry of Food, Nature Management and Fisheries (AID). b Cattle Feed Regulations 1986 and 1988. c For calves 50mg/kg is permitted.
Toxicology From the viewpoint of animal health (lead toxicity) as well as from the viewpoint of public health (lead levels in animal products above residue limits) the current intoxication was an extremely serious one. From the data collected by the AID (the difference between the amounts of feed delivered and recalled), an estimated thousand tons of lead-contaminated feed was actually consumed by the animals. These animals consumed about 1000 kg lead, over a period of one to four weeks. Naturally, enormous variations occurred between the various farms: based on the data obtained, the actual uptake varied between 1 and 370 g of lead per animal (averaged per farm). The mean uptake for all farms involved was 65 g of lead per animal. This amount, if administered in one (oral) dose, is lethal: the acute lethal dose for an adult cow is 6-60 g (Hapke 1988, Humphreys 1988). Heavy metals administered during a period of time are accumulated in the organs involved in their excretion: liver and kidney (Hoskam 1958, Sharma et al. 1982, Cheville 1988, Hapke 1988, Humphreys 1988). Furthermore, increased uptake will produce increased levels in milk and meat (Sharma et al. 1982, Hapke 1988, Humphreys 1988). Hence all bovine products from the farms involved had to be controlled scrupulously regarding the public health aspects. Marking of cattle In consultation with the MLNV, the MWVC, and the PVV, it was decided on 1 November that marking of the affected animals was necessary in order to be able to trace and identify them. Based on the observed levels of lead in feed and milk, lead levels well above the regulatory limits in liver and kidney (Nederlandse Staatscourant 1985, 1988) were expected, which prohibited consumption of these products. Also meat lead levels above that limit seemed likely. These limits are set by the Food and Drugs Act, and are presented in table 2. Criteria for the marking of animals were drafted by the CDI-DLO and the MLNV on 2 November. The starting point was the consideration that the use of
360
A. J. Baars et al. Table 2. Regulatory limits (Food and Drugs Act) for heavy metals in bovine products (in mg per kg fresh weight).
Lead Cadmium Mercury Arsenica
Milk
Meat
Liver
Kidney
0-05 0-005 0-01
0-4
0-05 0-05
1-0 1-0
0-05
0-1
0-5
1-5 3-0 0-1 0-5
—
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a Action limits (the Food and Drugs Act does not regulate arsenic limits).
contaminated feed was terminated on 30 October at the latest. The risk of lead levels above the limits in meat and/or organs from animals of a particular farm was considered negligible if the feed used on that farm had contained less than 10 mg lead per kg, and milk samples from that farm after 31 October showed lead concentrations of less than 0 • 025 mg per kg milk (or alternatively, if concentrations were less than 0-05 mg per kg milk in two consecutive samples taken on different days after 1 November). In that case marking of animals on that farm was considered unnecessary. Marking was deemed necessary if these criteria were not met. The PVV tagged over 15 000 animals (about 300 farms) along these lines in week 45 (4th-10th November, 1989). Almost identical criteria were applied regarding the milk. Milk from farms sampled in week 45 or thereafter was released for human consumption if it contained less than 0-026 mg lead per kg milk, or less than 0-051 mg per kg milk in two consecutive samples (Rijkskeuringsdienst van Waren 1989).
Predictions
The results of experiments by Vreman et al. (1986) were used to predict the lead levels in the animal products surviving the intoxication. These authors studied the carry-over of some heavy metals in dairy cattle; their findings, and the carryover factors calculated from their data are presented in table 3. The uncertainty of these carry-over factors, however, needs to be stressed: Vreman et al. (1986) administered a dose of 0-2 g lead per animal per day during several months, while cattle affected by the current intoxication consumed roughly 9 g lead per animal per day during one to four weeks (table 3). The carry-over factors calculated from Vreman et al. (1986), applied to the current intoxication, resulted in expected lead levels which are also presented in table 3. Obviously, lead levels well above the regulatory limits seemed very likely. Once the uptake of lead is terminated, the biological half-life of lead determines its decrease in animal organs (including milk). Reported values (Sharma et al. 1982, Tsuchiya 1986, Humphreys 1988) for this parameter vary from 18 days to 2 months. Hence, based on a worst case approximation it seemed possible that the cattle markings needed to be maintained for a period up to one year. On the basis of the levels of the other contaminating metals in the feed, problems were to be expected for cadmium only. Levels above regulatory limits for the other metals seemed very unlikely.
Lead intoxication in cattle
361
Table 3. Literature data, lead levels to feed and bovine products as per 1 November 1989, calculated carry-over factors, and predicted product levels. Product levels:*
Feed
Milk
Meat
Liver
Kidney
2-5 10 100-450
0-005 0-011 0-200
0-03 0-04 —
0-16 0-52 —
0-46 1-05 —
Milk
Meat
Liver
Kidney
Control Experiment1"
0-002 0-001
0-012 0-004
0-064 0-052
0-184 0-105
Predicted product levels:"
Milk
Meat
Liver
Kidney
Control15 Experiment1' Incident0 Carry-over factors:1* b
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At 100 mg lead per kg feed At 450 mg lead per kg feed
e
0-10 0-45'
0-4 1-8"
e
5 23 c
10e 45 e
a
mg lead per kg fresh weight. •"Control' and 'Experiment' are from Vreman et al. (1986) (see text). c 'Incident' represents the current intoxication as caused by lead-contaminated feed. d The carry-over factor is defined as 'lead level in bovine product' divided by 'lead level in feed'. 'Above regulatory limits (table2). Starting point for calculations is a feed uptake of 20 kg (dry material) per animal per day. On the basis of a mean uptake of 65 g lead per animal during a period of intoxication of one to four weeks (see text), the theoretial lead level in feed must have been 450 mg/kg for a feeding period of one week, and 100 mg/kg for a feeding period of one month.
Results Lead in meat and offals of cattle slaughtered in the period during which this cattle was marked, was measured by the RIKILT-DLO. Indeed levels well above the regulatory limits for liver and kidney were established. Only in meat were the levels measured below the regulatory limit. Significant concentrations of cadmium were not found, and it could be concluded that levels above the cadmium limits did not occur. Milk lead levels were continuously monitored, and revealed a rapid decrease as illustrated in figure 1. Already in week 45 the mean concentration was below the regulatory limit. Blood samples taken in weeks 49 and 50 allowed a first approximation of the kinetics of lead in the affected animals. Assuming a first-order elimination process, a biological half-time of 10-5 days was derived, with an SEM of 1-1 days. Hence a half-life for lead of 23 days should apply to 99% of the animals involved. The scarce data of offals available by that time were generally in agreement with the estimation. Also Tsuchiya (1986) reported no difference between the half-life of lead in blood and in soft tissues. Therefore the cattle-marking was terminated around 10 January 1990. About ten farms, however, were excepted from this. In their cattle very high amounts of lead were observed, indicating a risk that even on 10 January the levels in offals would be above the regulatory limits. Ongoing analyses carried out with blood and organ samples from these animals warranted their release by the end of January.
362
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J. Baars et al.
Lead in milk Average concentration per day 0.14 0.12
^ °- 10 I 1 0.08
£
0.06 0.04 0.02 0
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Day Figure 1. The decline of the mean lead level in milk (in mgPb per litre) during the first weeks of the incident. The regulatory limit is represented by a dashed line. Data: Regional Public Health Inspectorate at Leeuwarden (IGB), and the Association of Cooperating Dairy Factories, Friesland (Leeuwarden).
Lead in livers and kidneys Average content per week Liver
46 47 48 49 50 51 52
44
45
46
47
48
49 50 Week
51
52
1
2
1
Figure 2. The decline of the mean lead levels in livers and kidneys (in mg per kg dry material) during the incident (week 44—1989 to week 2—1990). On this dry-weight basis, levels of 3-5 mgPb per kg dry liver, and 7-0 mgPb per kg dry kidney can be taken as the regulatory limits. Number of samples Week no.
Farms Livers Kidneys
44
45
46
47
48
49
50
51
52
01
02
19 22 27
18 11 21
17 12 22
18 25 22
14 23 25
27 48 48
26 40 40
19 33 33
15 20 20
13 21 21
6 7 7
Data: State Service for Cattle and Meat Inspection (RVV), DLO-State Institute for Quality Control of Agricultural Products (RIKILT-DLO), and Animal Health Service in North-Netherlands (GDNN).
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Lead intoxication in cattle
363
Evaluation The mean amounts of lead in livers and kidneys of intoxicated cattle are presented in figure 2. Clearly the levels decreased sharply during the period from week 44 to week 48. It should be noted, however, that the data of week 44 originate from animals that died of acute lead intoxication. In the weeks following the data refer to animals alive at the time of slaughter. If (also) live animals had been analysed in week 44, the mean levels in that week would probably have been somewhat lower. The levels observed in weeks 44 and 45 are generally in agreement with the expectations summarized in table 3. Only the levels in meat (data not given) appeared to be lower than expected. Apparently the carry-over to meat is reduced if the uptake is high. From the data in figure 1 it is possible to derive a half-life for lead in milk of 4-6 days. This is about 15% longer than the half-life estimated by the IGB (Rijkskeuringsdienst van Waren 1989), who used a smaller but better denned set of data. Likewise, figure 2 allows the deduction of a half-life of 7*4 days for lead in offals. The mean lead blood levels as measured in weeks 44 and 45 are illustrated in figure 3, and show a clear dose-response relation. The time course of lead levels
Lead in blood Average content in weeks 44 and 45 0,40
0,30
£
0,20
0,10 -
0-100
100-500
500-1000
1000-1500
>1500
Content in feed (mg/kg) Figure 3. Mean lead levels in blood (in mg Pb per litre) of cattle during weeks 44 and 45 (1989), related to the different feed levels. Feed level (mg/kg)
Farms Samples
0-100
100-500
500-1000
1000-1500
>1500
17 69
7 31
42 358
60 509
24 160
Data: Animal Health Service in North-Netherlands (GDNN), and DLO-Central Veterinary Institute (CDI-DLO).
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A. J. Baars et al.
in blood beyond week 45 cannot be established reliably, because in later weeks only a limited number of blood samples were analysed. The levels measured in weeks 1 and 2 (1990), however, were all well below 0-1 mg per 1, indicating the return to a normal state of health of the animals involved. Beyond doubt, the EDTA-therapy (Merck-AUV 1989), immediately applied, significantly reduced the number of casualties. Only about 30 animals died as a direct result of the lead intoxication, while some 40 animals had to be slaughtered. The exposure data suggest that a far higher mortality would have occurred if adequate treatment had not been applied so rapidly. Following the incident, veterinary inspections were carried out on a number of farms where high lead levels were observed in blood and/or offals during the incident. No morbid symptoms were observed, and no other consequences of a lead intoxication, such as low birth-weights, early births, or abortions, were seen either. Thanks to the immediate action of the veterinarians in the two northern provinces and the close cooperation of all authorities involved, the damage for the individual farms was limited as far as possible. Export interests were also protected. The risk for the human consumer was smaller than feared at first, and hence the measure to tag the animals could soon be terminated. References CHEVILLE, N. F., 1988, Introduction to Veterinary Pathology (Ames: Iowa State University Press), p. 449. HAPKE, H. J., 1988, Blei. Toxikologie für Veterinärmediziner, 2nd edn (Stuttgart: Ferdinand Enke Verlag), pp. 191-196. HOSKAM, E. G., 1958, Vergiftiging in de praktijk—lood (Intoxications in thefield—lead).Tijdschrift voor Diergeneeskunde, 83, 413-423. HUMPHREYS, D. J., 1988, Lead. Veterinary Toxicology, 3rd edn (London: Ballière Tindall), pp. 49-58. MERCK-AUV, 1989, Dierenartsen behandelen loodvergiftigde koeien (Veterinarians are treating leadintoxicated cows). Merck Reagentia, 2, 41-42. Nederlandse Staatscourant, 1985, 1988, Regeling normen zware metalen (Dutch Governmental Newspaper, 1985, 1988, Regulatory limits for heavy metals), No. 58, 22 March 1985; No. 121, 27 June 1988. RIJKSKEURINGSDIENST VAN WAREN TE LEEUWARDEN, 1989, De besmetting van veevoer met lood in
oktober/november 1989 (Regional Public Health Inspectorate at Leeuwarden, 1989, The leadcontamination of cattle feed in October/November 1989). Annual Report 1989, pp. 19-25. SHARMA, R. P., STREET, J. C., SHUPE, J. L., and BOURCIER, D. R., 1982, Accumulation and depletion
of cadmium and lead in tissues and milk of lactating cows fed small amounts of these metals. Journal of Dairy Science, 65, 972-979. TSUCHIYA, K., 1986, Lead. Handbook on the Toxicology of Metals, 2nd edn, edited by L. Friberg, G. F. Nordberg and V. B. Vouk (Amsterdam: Elsevier), Vol. II, pp. 298-353. VREMAN, K., VAN DER VEEN, N. G., VAN DER MOLEN, E. J., and DE RUIG, W. G., 1986, Transfer of
cadmium, lead, mercury, and arsenic from feed into milk and various tissues of dairy cows—chemical and pathological data. Netherlands Journal of Agricultural Sciences, 34, 129-144.
