CASE REPORT AMMONIATED MERCURY TOXICITY IN CATTLE F. IRVING
AND
Introduction Recent outbreaks of mercury poisoning in cattle have generally involved the ingestion of organic mercurial compounds (2,13). When mercurial preparations were widely used in treatment, inorganic and elemental mercury poisonings were common (7). This paper describes the clinical and laboratory findings in a group of heifers treated topically with an inorganic mercurial ointment. One animal was experimentally treated with the same ointment and the uptake and excretion of mercury was observed. History Thirteen Holstein-Blonde d'Aquitaine crossbred heifers, six to seven months old, were shipped from the Ottawa Valley to the Guelph area in November, 1973. They were vaccinated against infectious bovine rhinotracheitis (IBR) by the intranasal route and given intramuscular injections of vitamins A, D and E on arrival. The heifers were housed in a pole barn and fed a diet of grass, hay and oats supplemented with concentrate. One animal had ringworm lesions on arrival. Within two weeks, ringworm spread rapidly through the whole group of heifers and daily treatment for the disease with 5% ammoniated mercury ointment' was then instituted. The lesions were scarified with a steel comb and the ointment was applied topically. Although the ointment was applied sparingly, the cattle tended to lick each other after each application. Three weeks after arrival, the heifers were divided into three groups and placed in adjacent pens in the same barn. One group of three animals had few ringworm lesions and treatment of these animals was discontinued. These heifers maintained satisfactory growth
D. G. BuTLER*
rates and never did appear clinically ill. The heifers in the other two groups had extensive
skin lesions and the treatment was continued. During the fourth week of treatment, one animal (Case No. 1) developed posterior paresis. After five weeks of treatment, many heifers had diarrhea and the feed was limited to hay and rolled oats only. As the ringworm was not responding to therapy and the heifers were not gaining weight the treatment with ammoniated mercury was stopped. Four more heifers showed signs of illness from four days to three weeks after the mercury treatment was discontinued. Clinical Findings Information regarding the affected heifers and the clinical signs on admission is summarized in Table I. Case No. 1 - This heifer was found in sternal recumbency during the fourth week of treatment with ammoniated mercury. When first examined (day 1) the heifer had a temperature of 39.0°C, a heart rate of 96 per minute and a respiratory rate of 30 per minute. The heifer was thin and had widespread lesions of ringworm. Posterior paresis and a generalized muscle tremor were present. The heifer continued to eat and drink normally. On day 2, tongue and jaw tone were reduced, the anal reflex was slow and the rumen was static. The animal was observed to cough after drinking water. The heifer was bawling, chewing and struggling violently on the morning of day 3 and died after several hours.
Case No. 2 - Four days after the ammoniated mercury treatment was discontinued, the heifer was observed to have posterior ataxia and a mild generalized muscle tremor. When first examined, the heifer had a temperature of 'Department of Clinical Studies, Ontario Vet- 39.4°C, heart rate of 100 per minute and a erinary College, University of Guelph, Guelph, respiratory rate of 92 per minute. She was Ontario. Paper written by senior author as part of the reluctant to stand, but when standing had a requirement for a Diploma in Large Animal base narrow stance behind, tending to stand either with one foot on the other or with the Medicine. 1Thydragyri Ammoniate (5%), Drug Trading hind legs crossed. Respiration was rapid and Company, Toronto, Ontario. shallow with increased bronchial tones evident ?60 CAN. VET. JOUR., vol. 16, no. 9, September, 1975
MERCURY TABLE I CLINICAL DATA IN FIvE CROSSBRED HEIFERs, EIGHT TO NINE MONTHS OLD TREATED WITH 5% AMMONIATED MERCURY OINTMENT (CONTAINING 3.8% MERCURY) FROM NOVEMBER 20, 1973 UNTIL DECEMBER 23, 1973
Case No. Date Admitted Weight Condition
1 Dec. 19, 1973 257 kg
2 Dec. 27, 1973 207 kg
Demeanor Rectal Temp (C°) Skin Lesions
Good Dull 38.9 Ringworm
Poor Dull 39.7 Ringworm Craterous lesions Punctate lesions (around anus)
Oral Lesions
Not seen
Erosions
Respiratory System Nervous System
No abnormalities Paresis
Dyspnea
Other Abnormalities Abnormal Laboratory Findings Kidney Inorganic Mercury Levels Outcome
3 Dec. 27, 1973 172 kg Poor (small) Dull 40 Ringworm Craterous lesions Punctate lesions (around anus and vulva) Alopecia Erosions Drooled saliva No abnormalities Posterior ataxia
4 5 Jan. 13, 1974 Jan. 14, 1974 181 kg 193 kg
Poor Dull 39.1
Ringworm
Fair Bright 40.1 Ringworm
Not seen
Not seen
Dyspnea
Dyspnea
Posterior ataxia
Not seen
Muscle tremor None
Posterior ataxia Muscle tremor None Corneal ulcer
Diarrhea
Mild neutrophilia
Mild neutrophilia
BUN 48 mg%
None
Swollen joints None
Not done
116 ppm
54 ppm
47 ppm
28 ppm
Died
Survived
Survived Prolonged convalescence
Died
Survived
on auscultation. Rumen movement was slow and the feces contained poorly digested ma-
The animal was observed to stand for long periods with her mouth open drooling saliva. terial. Generalized ringworm lesions were There was a corneal ulcer on the left eye. The present as well as encrustations of hair and punctate lesions around the anus were more debris along the back which when lifted off numerous than in the second case and exrevealed a hairless crater 0.5-1.0 cm in diam- tended down the lips of the vulva. An area of eter. There were punctate lesions up to 0.5 cm alopecia in the escutcheon extended down the in diameter around the anus. The heifer stood medial aspects of the hind legs. The ataxia was with her tail head extended and strained. similar to, but not as marked as in Case No. 2 Shallow circular erosions up to one centimeter and the animal remained standing. This animal in diameter were present on the soft palate. also made an extremely slow recovery. There were erosions up to 2 cm in diameter on the ventral surface of the tongue. The aniCase No. 4 - This heifer showed anorexia mal made an extremely slow recovery. An im- and dyspnea three weeks after the mercury provement in demeanor and appetite was seen treatment was stopped. She was in poor body within ten days but it took six weeks to make condition with generalized ringworm lesions. a significant gain in body weight. On initial examination the temperature was 390C, heart rate 100 per minute and the Case No. 3 - This heifer developed signs respiratory rate was 80 per minute. The aniat the same time as Case No. 2. She had a mal exhibited ataxia similar to Cases No. 2 temperature of 400C, a heart rate of 90 per and 3. Increased vesicular sounds were heard minute and a respiratory rate of 42 per minute. over all lung fields, rumen movements were The animal was in poor body condition and slow and diarrhea was present. On day 2 the had similar skin and oral lesions as Case No. 2. heifer had posterior paresis and the diarrhea 261
CANADIAN VETERINARY JOURNAL
was more severe. The animal developed terminal convulsions and died on day 3.
TABLE II TOXICOLOGICAL DATA IN CASE No. 4 OBTAINED BY ANALYSIS OF KIDNEY TISsUE (AN HOMOGENATE OF CORTEX AND MEDULLA) OBTAINED AT NECROPSY FOLLOWING TREATMENT WITH 5% AMMONIATED MERCURY OINTMENT (3.8% MERCURY) FROM NOVEMBER 20, 1973 UNTIL DECEMBER 23, 1973
Case No. 5 - The day after Case No. 4 was first examined, this heifer was seen to be ataxic. The heifer was in poor body condition and was dyspneic. She had a temperature of 40.1°C, a heart rate of 90 per minute and a respiratory rate of 40 per minute. A bilateral, Concentration Substance (ppm on a wet weight basis) mucoid nasal discharge was seen and increased vesicular sounds could be heard over the chest. 0.01 Mercury Widespread ringworm lesions and encrusta- Methyl 5.5 Mercury Not detected tions of hair and debris, similar to those seen Arsenic 0.31 in Cases No. 2 and 3, were present. The ataxia Lead resembled that seen in the previous cases. The hock and fetlock joints of its hind legs were toxicological analysis of kidney tissue (an swollen. This animal also made an extremely homogenate of cortex and medulla) obtained slow recovery. from the second animal to die (Case No. 4) are listed in Table II. In those animals which Clinical Pathology survived, mercury assays were performed on There were no consistent changes in hae- kidney tissue collected by biopsy. The findings matology (hemoglobin, PCV, WBC counts) are summarized in Table I. Urine and blood or blood chemistry (BUN and serum proteins). from Cases No. 2 and 3 contained less than A mild proteinuria, however, was consistently 0.01 ppm of mercury. A sample of the ointdetected on urinalysis (Table I). ment was found to contain 3.8% mercury and less than 0.01 ppm of methyl mercury. Gross Pathology There were no significant lesions at nec- Experimental Reproduction of Mercury ropsy in Cases No. 2, 3, 4, 5. Pulmonary con- Toxicity gestion was the only visible lesion in Case No. A seven month old Charolais-Holstein steer 1. There was hemorrhage in the upper respira- weighing 178 kg was used to monitor the uptory tract and atelectasis of the apical and take and toxic effects of the 5% ammoniated cardiac lobes of the lung in Case No. 4. mercury ointment. The animal had suffered Ecchymotic and paintbrush hemorrhage of from chronic pneumonia, was small for its age the epicardium were also present in this and had ringworm lesions about the left eye animal. and on the rump. The ointment was applied to the ringworm lesions and the muzzle daily Histopathology to simulate the conditions in the outbreak Fibrinoid degeneration was evident in the reported in which heifers were observed lickmedia of a few arterioles in the central nervous ing ointment following its topical application. system in Case No. 1. Case No. 4 showed The ointment was applied for 34 consecutive some vacuolation of smooth muscle cells in days and a total of one pound was used. the tunica media of arterioles of the brain. Kidney biopsies for mercury assay were perThere was also some oedema with mild mono- formed at three, 53 and 140 days after mernuclear infiltration of the choroid plexus at cury ointment application was stopped. the Foramen of Luska in this heifer. Mononuclear infiltration of the tunica adventitia and Results media of leptomeningeal vessels of the cord The experimental steer did not show any was present. There was a mild mononuclear clinical signs of mercury poisoning. There were infiltrate with some polymorphonuclear cells no detectable clinicopathological changes. within the meninges. Neither the application of the ointment or There was some vacuolation of Purkinje cells repeated kidney biopsies had any apparent and hyaline degeneration of myocardium in effect on the animal's appetite or general wellthe heart of Case No. 4. Pulmonary congestion being. The ringworm lesions showed no reand oedema was present in both heifers. sponse to treatment with ammoniated mercury ointment. The level of mercury in the kidney Toxicology of this animal, using tissue obtained by Tissue mercury levels were not determined peritoneal biopsy technique, was higher retrothan in the first animal that died. The results of in three of the heifers that showed clinical 262
MERCURY
signs (Cases No. 3, 4 and 5). Analysis of tissue obtained by kidney biopsy three, 52 and 140 days after the final application of the ointment revealed 67, 28 and 1 ppm of mercury respectively. Discussion
Ammoniated mercury has been in use since the last century (3) as a parasiticide and skin antiseptic for animals. Poisoning has been associated with the use of the ointment in dogs (10). In human medicine the incidence of intoxication from ammoniated mercury ointment is regarded as being sufficiently high to condemn its use (5). Harvey (7) described apparent inorganic mercury poisoning in animals treated for ringworm. Ammoniated mercury was not incriminated in these cases. Paresis was the major presenting sign and there was an absence of other manifestations. Chronic intoxication in humans is a well documented result of industrial exposure to inorganic mercury (11). The classical signs include tremor and psychological disturbances. The nervous signs seen in this episode of inorganic mercury poisoning closely resembles those described for organic mercury poisoning. Motor incoordination giving the appearance of muscular weakness, tremor, reluctance of animals to stand and paresis are typically seen in organic mercury poisoning in cattle (2, 8). Skin lesions are frequently seen with elemental mercury poisoning (12) and less often in organic mercury toxicosis (4, 13). In these cases, the presence of numerous ringworm lesions, and the use of a steel comb to scarify these lesions prior to the application of ammoniated mercury ointment, made it difficult to assess the degree of dermal change attributable to mercury toxicosis. The distinctive punctate perianal lesions were not related to sites of application of the ointment. Similar punctate eruptions and vesicle formation have been described in human hypersensitivity reactions to inorganic mercurial ointments (5). The pustular lesions were similar to those described in metallic poisoning (12). Presumably, skin irritation developed slowly following the application of the ointment as mercury was ionized in the tissues (1). Oral lesions are associated with acute mercury toxicity but do not appear to be a frequent finding in chronic mercury poisoning in cattle. Reinders (12) reports oral erosions in one of a large number of cows showing signs following the ingestion of metallic mercury. The occurrence of oral lesions in two of the five cases described here seems to be a high incidence. 263
Respiratory system involvement is often poisoning. Bronchitis and bronchopneumonia were reported in an outbreak of metallic mercury poisoning (12). Japanese workers (4, 13) record bronchial catarrh as a characteristic finding in organic
seen in chronic mercury
mercury toxicosis. The absence of characteristic clinicopathological findings and gross postmortem lesions is typical of chronic mercury poisoning. Degeneration of the tunica media of arterioles of the brain and particularly of leptomeningeal vessels of the spinal cord are characteristic findings in mercury poisoning (9). The degeneration of the Purkinje network of the heart seen in the second postmortem is also a consistent finding in mercury poisoning. Generally, there is neuronal degeneration but this was not observed in these cases. Other investigators (4, 8) recorded individual differences among cattle and their response to mercury intoxication. There was a poor correlation between the severity of clinical signs and kidney mercury levels in this outbreak of poisoning. The kidney mercury levels in the experimental steer indicate ready absorption of ammoniated mercury following cutaneous application and ingestion. There was a rapid fall in kidney mercury levels in this animal following its removal from mercury exposure. Kidney mercury levels do not appear to fall as rapidly following organic mercury poisoning in humans (6). Suimmary Deaths occurred in cattle treated for ringworm with an ointment containing ammoniated mercury (3.8% mercury). The clinical signs observed were a gradual loss of body condition, ataxia and paresis. Affected animals exhibited pustular skin lesions, erosions of the oral mucosae and pneumonia. Pulmonary congestion and ecchymotic and paintbrush hemorrhages on the epicardium and endocardium were seen at necropsy. Histopathological changes were observed in blood vessels of the brain and spinal cord and in the Purkinje cells and myocardium of the heart. An animal experimentally treated with the same ointment exhibited no clinical signs but had kidney mercury levels comparable to the poisoned animals.
Re"sumie Des bovins sont morts a la suite d'un traitement de la teigne avec un onguent qui contenait du mercure precipite blanc (3.8% de mercure). Les signes cliniques se traduisirent
CANADIAN VETERINARY JOURNAL
par une perte graduelle de condition, de l'ataxie et de la paresie. Les animaux malades presentaient des pustules cutanees, des erosions de la muqueuse buccale et de la pneumonie. Lors de la necropsie, on observa de la congestion pulmonaire, des ecchymoses et des hemorragies "en coup de pinceau" sur l'epicarde, ainsi que sur l'endocarde. L'histopathologie revela la presence de lesions dans les vaisseaux sanguins du cerveau et de la moelle epiniere, ainsi que dans les fibres musculaires et les cellules de Purkinje du cceur. Le traitement experimental d'un bouvillon avec cet onguent ne provoqua pas de signes cliniques; la quantite de mercure qu'on recouvra de ses reins s'avera cependant comparable 'a celle des memes organes des sujets empoisonnes. Acknowledgments We wish to express our appreciation to Drs. R. B. Miller, P. B. Little and G. W. Thomson of the Department of Pathology, University of Guelph, who performed the necropsies, and to Mr. H. Funnell, Veterinary Services, O.M.A.F. who performed the toxicological analyses. References 1. BIDSTRUP, P. L. Toxicity of Mercury and its Compounds. London, England: Elsevier Publishing Company. 1964. 2. BOLEY, L. E., C. C. MORRILL and R. GRAHAmI. Evidence of mercury poisoning in
feeder calves, North American Vet. 22: 161164. 1941. 3. DUN, F. Veterinary Medicines - Their Actions and Uses. New York: William R. Jenkins. 1883. 4. FUJIMOTO, Y., K. OMSMMA, H. SATOH and Y. OHTA. Pathological studies on poisoning in cattle. Jap. J. vet. Res. 4: 17-32. 1956. 5. GOODMAN, L. S. and A. GLMAN. The Pharmacological Basis of Therapeutics, Fourth Edition. New York: The Macmillan Company. 1970. 6. HARTUNG, R. and B. D. DnMAN. Environmental Mercury Contamination. Ann Arbor, Michigan: Ann Arbor Science Publishing Co. 1972. 7. HARVEY, F. T. Mercurialism in cattle. Vet. Rec. 12: 328-329. 1932. 8. HERINGSTAD, R. R., C. K. W murET Am, B. BEYER, 0. MICKELSEN and M. J. ZABIK. Chronic methylmercury toxicosis in calves. J. Am. vet. med. Ass. 160: 173-182. 1972.
9. JUBB, K. V. J. and P. C. KENNEDY. Pathology of Domestic Animals, Second Edition. London, England: Academic Press. 1970. 10. LANDER, G. D. Veterinary Toxicology. London, England: Bailliere, Tindall and Cox.
1912. 11. MILLER, M. W. and T. W. CLARESON. Mercury, Mercurials and Mercaptans. Springfield, Illinois: Charles C. Thomas. 1973. 12. REINDERS, J. S. Mercury poisoning in cattle. Neth. J. vet. Sci. 4: 79-84. 1972. 13. SONODA, M., R. NAKAMURA, K. Too, A. MATSUHASHI, H. ISHIMOTO, R. SASAKI, K. ISHIDA and M. TAKAHASHI. Clinical studies on mercury poisoning in cattle. Jap. J. vet. Res. 4: 5-16.1956.
ANALYSE DE VOLUME Vertebrate Hard Tissues. L. B. Halstead. Pu- donne une liste de ref6rences bibliographiques blie par Springer Verlag, New York. 1974. plus approfondies et l'autre une classification 180 pages. Prix $7.80. taxonomique simplifiee des vertebres. Les dessins et les schemas sont bons, parfois excelCe petit ouvrage tente, de fa,on d'ailleurs lents. Les photographies sont egalement tres fort heureuse, de realiser une synthese des bonnes, de facon g6nerale. Certaines figures connaissances sur les tissus les plus durs des (13.2, par exemple) ne sont toutefois pas tres vertebres. L'enjeu, s'il est valable, est d'enver- suggestives; d'autres (13.3) tres conventiongure. Int6grer, dans un meme texte, des aspects nelles et classiques; certaines (13.5) tres d6aussi divers que la biochimie, la morphologie monstratives et vraiment nouvelles. Comme descriptive et surtout comparee, la pathologie, dans toute premiere edition, il existe quelques des notions de pal6ontologie et d'evolution au erreurs typographiques mineures (ex.: pterysens darwinien comme au sens ontog6nique goideus dans la fig. 17.2). du terme, constitue une entreprise extremeEn conclusion, ce petit livre constitue une ment difficile. Forcement, certains aspects de bonne synthese d'un sujet extremement vaste la matiere doivent rester dans l'ombre. et il atteint certainement le but que l'auteur Le livre est divise en trois parties: aspects s'etait fixe: "I hope this book will encourage mol6culaires et cellulaires, les tissus et, finale- students to delve deeper or even eventually to ment le squelette. La matiere est repartie en- enter the expanding field of calcified tissue tre 21 chapitres et deux appendices dont l'un research." J. Pi4rard. 264
AND
Introduction Recent outbreaks of mercury poisoning in cattle have generally involved the ingestion of organic mercurial compounds (2,13). When mercurial preparations were widely used in treatment, inorganic and elemental mercury poisonings were common (7). This paper describes the clinical and laboratory findings in a group of heifers treated topically with an inorganic mercurial ointment. One animal was experimentally treated with the same ointment and the uptake and excretion of mercury was observed. History Thirteen Holstein-Blonde d'Aquitaine crossbred heifers, six to seven months old, were shipped from the Ottawa Valley to the Guelph area in November, 1973. They were vaccinated against infectious bovine rhinotracheitis (IBR) by the intranasal route and given intramuscular injections of vitamins A, D and E on arrival. The heifers were housed in a pole barn and fed a diet of grass, hay and oats supplemented with concentrate. One animal had ringworm lesions on arrival. Within two weeks, ringworm spread rapidly through the whole group of heifers and daily treatment for the disease with 5% ammoniated mercury ointment' was then instituted. The lesions were scarified with a steel comb and the ointment was applied topically. Although the ointment was applied sparingly, the cattle tended to lick each other after each application. Three weeks after arrival, the heifers were divided into three groups and placed in adjacent pens in the same barn. One group of three animals had few ringworm lesions and treatment of these animals was discontinued. These heifers maintained satisfactory growth
D. G. BuTLER*
rates and never did appear clinically ill. The heifers in the other two groups had extensive
skin lesions and the treatment was continued. During the fourth week of treatment, one animal (Case No. 1) developed posterior paresis. After five weeks of treatment, many heifers had diarrhea and the feed was limited to hay and rolled oats only. As the ringworm was not responding to therapy and the heifers were not gaining weight the treatment with ammoniated mercury was stopped. Four more heifers showed signs of illness from four days to three weeks after the mercury treatment was discontinued. Clinical Findings Information regarding the affected heifers and the clinical signs on admission is summarized in Table I. Case No. 1 - This heifer was found in sternal recumbency during the fourth week of treatment with ammoniated mercury. When first examined (day 1) the heifer had a temperature of 39.0°C, a heart rate of 96 per minute and a respiratory rate of 30 per minute. The heifer was thin and had widespread lesions of ringworm. Posterior paresis and a generalized muscle tremor were present. The heifer continued to eat and drink normally. On day 2, tongue and jaw tone were reduced, the anal reflex was slow and the rumen was static. The animal was observed to cough after drinking water. The heifer was bawling, chewing and struggling violently on the morning of day 3 and died after several hours.
Case No. 2 - Four days after the ammoniated mercury treatment was discontinued, the heifer was observed to have posterior ataxia and a mild generalized muscle tremor. When first examined, the heifer had a temperature of 'Department of Clinical Studies, Ontario Vet- 39.4°C, heart rate of 100 per minute and a erinary College, University of Guelph, Guelph, respiratory rate of 92 per minute. She was Ontario. Paper written by senior author as part of the reluctant to stand, but when standing had a requirement for a Diploma in Large Animal base narrow stance behind, tending to stand either with one foot on the other or with the Medicine. 1Thydragyri Ammoniate (5%), Drug Trading hind legs crossed. Respiration was rapid and Company, Toronto, Ontario. shallow with increased bronchial tones evident ?60 CAN. VET. JOUR., vol. 16, no. 9, September, 1975
MERCURY TABLE I CLINICAL DATA IN FIvE CROSSBRED HEIFERs, EIGHT TO NINE MONTHS OLD TREATED WITH 5% AMMONIATED MERCURY OINTMENT (CONTAINING 3.8% MERCURY) FROM NOVEMBER 20, 1973 UNTIL DECEMBER 23, 1973
Case No. Date Admitted Weight Condition
1 Dec. 19, 1973 257 kg
2 Dec. 27, 1973 207 kg
Demeanor Rectal Temp (C°) Skin Lesions
Good Dull 38.9 Ringworm
Poor Dull 39.7 Ringworm Craterous lesions Punctate lesions (around anus)
Oral Lesions
Not seen
Erosions
Respiratory System Nervous System
No abnormalities Paresis
Dyspnea
Other Abnormalities Abnormal Laboratory Findings Kidney Inorganic Mercury Levels Outcome
3 Dec. 27, 1973 172 kg Poor (small) Dull 40 Ringworm Craterous lesions Punctate lesions (around anus and vulva) Alopecia Erosions Drooled saliva No abnormalities Posterior ataxia
4 5 Jan. 13, 1974 Jan. 14, 1974 181 kg 193 kg
Poor Dull 39.1
Ringworm
Fair Bright 40.1 Ringworm
Not seen
Not seen
Dyspnea
Dyspnea
Posterior ataxia
Not seen
Muscle tremor None
Posterior ataxia Muscle tremor None Corneal ulcer
Diarrhea
Mild neutrophilia
Mild neutrophilia
BUN 48 mg%
None
Swollen joints None
Not done
116 ppm
54 ppm
47 ppm
28 ppm
Died
Survived
Survived Prolonged convalescence
Died
Survived
on auscultation. Rumen movement was slow and the feces contained poorly digested ma-
The animal was observed to stand for long periods with her mouth open drooling saliva. terial. Generalized ringworm lesions were There was a corneal ulcer on the left eye. The present as well as encrustations of hair and punctate lesions around the anus were more debris along the back which when lifted off numerous than in the second case and exrevealed a hairless crater 0.5-1.0 cm in diam- tended down the lips of the vulva. An area of eter. There were punctate lesions up to 0.5 cm alopecia in the escutcheon extended down the in diameter around the anus. The heifer stood medial aspects of the hind legs. The ataxia was with her tail head extended and strained. similar to, but not as marked as in Case No. 2 Shallow circular erosions up to one centimeter and the animal remained standing. This animal in diameter were present on the soft palate. also made an extremely slow recovery. There were erosions up to 2 cm in diameter on the ventral surface of the tongue. The aniCase No. 4 - This heifer showed anorexia mal made an extremely slow recovery. An im- and dyspnea three weeks after the mercury provement in demeanor and appetite was seen treatment was stopped. She was in poor body within ten days but it took six weeks to make condition with generalized ringworm lesions. a significant gain in body weight. On initial examination the temperature was 390C, heart rate 100 per minute and the Case No. 3 - This heifer developed signs respiratory rate was 80 per minute. The aniat the same time as Case No. 2. She had a mal exhibited ataxia similar to Cases No. 2 temperature of 400C, a heart rate of 90 per and 3. Increased vesicular sounds were heard minute and a respiratory rate of 42 per minute. over all lung fields, rumen movements were The animal was in poor body condition and slow and diarrhea was present. On day 2 the had similar skin and oral lesions as Case No. 2. heifer had posterior paresis and the diarrhea 261
CANADIAN VETERINARY JOURNAL
was more severe. The animal developed terminal convulsions and died on day 3.
TABLE II TOXICOLOGICAL DATA IN CASE No. 4 OBTAINED BY ANALYSIS OF KIDNEY TISsUE (AN HOMOGENATE OF CORTEX AND MEDULLA) OBTAINED AT NECROPSY FOLLOWING TREATMENT WITH 5% AMMONIATED MERCURY OINTMENT (3.8% MERCURY) FROM NOVEMBER 20, 1973 UNTIL DECEMBER 23, 1973
Case No. 5 - The day after Case No. 4 was first examined, this heifer was seen to be ataxic. The heifer was in poor body condition and was dyspneic. She had a temperature of 40.1°C, a heart rate of 90 per minute and a respiratory rate of 40 per minute. A bilateral, Concentration Substance (ppm on a wet weight basis) mucoid nasal discharge was seen and increased vesicular sounds could be heard over the chest. 0.01 Mercury Widespread ringworm lesions and encrusta- Methyl 5.5 Mercury Not detected tions of hair and debris, similar to those seen Arsenic 0.31 in Cases No. 2 and 3, were present. The ataxia Lead resembled that seen in the previous cases. The hock and fetlock joints of its hind legs were toxicological analysis of kidney tissue (an swollen. This animal also made an extremely homogenate of cortex and medulla) obtained slow recovery. from the second animal to die (Case No. 4) are listed in Table II. In those animals which Clinical Pathology survived, mercury assays were performed on There were no consistent changes in hae- kidney tissue collected by biopsy. The findings matology (hemoglobin, PCV, WBC counts) are summarized in Table I. Urine and blood or blood chemistry (BUN and serum proteins). from Cases No. 2 and 3 contained less than A mild proteinuria, however, was consistently 0.01 ppm of mercury. A sample of the ointdetected on urinalysis (Table I). ment was found to contain 3.8% mercury and less than 0.01 ppm of methyl mercury. Gross Pathology There were no significant lesions at nec- Experimental Reproduction of Mercury ropsy in Cases No. 2, 3, 4, 5. Pulmonary con- Toxicity gestion was the only visible lesion in Case No. A seven month old Charolais-Holstein steer 1. There was hemorrhage in the upper respira- weighing 178 kg was used to monitor the uptory tract and atelectasis of the apical and take and toxic effects of the 5% ammoniated cardiac lobes of the lung in Case No. 4. mercury ointment. The animal had suffered Ecchymotic and paintbrush hemorrhage of from chronic pneumonia, was small for its age the epicardium were also present in this and had ringworm lesions about the left eye animal. and on the rump. The ointment was applied to the ringworm lesions and the muzzle daily Histopathology to simulate the conditions in the outbreak Fibrinoid degeneration was evident in the reported in which heifers were observed lickmedia of a few arterioles in the central nervous ing ointment following its topical application. system in Case No. 1. Case No. 4 showed The ointment was applied for 34 consecutive some vacuolation of smooth muscle cells in days and a total of one pound was used. the tunica media of arterioles of the brain. Kidney biopsies for mercury assay were perThere was also some oedema with mild mono- formed at three, 53 and 140 days after mernuclear infiltration of the choroid plexus at cury ointment application was stopped. the Foramen of Luska in this heifer. Mononuclear infiltration of the tunica adventitia and Results media of leptomeningeal vessels of the cord The experimental steer did not show any was present. There was a mild mononuclear clinical signs of mercury poisoning. There were infiltrate with some polymorphonuclear cells no detectable clinicopathological changes. within the meninges. Neither the application of the ointment or There was some vacuolation of Purkinje cells repeated kidney biopsies had any apparent and hyaline degeneration of myocardium in effect on the animal's appetite or general wellthe heart of Case No. 4. Pulmonary congestion being. The ringworm lesions showed no reand oedema was present in both heifers. sponse to treatment with ammoniated mercury ointment. The level of mercury in the kidney Toxicology of this animal, using tissue obtained by Tissue mercury levels were not determined peritoneal biopsy technique, was higher retrothan in the first animal that died. The results of in three of the heifers that showed clinical 262
MERCURY
signs (Cases No. 3, 4 and 5). Analysis of tissue obtained by kidney biopsy three, 52 and 140 days after the final application of the ointment revealed 67, 28 and 1 ppm of mercury respectively. Discussion
Ammoniated mercury has been in use since the last century (3) as a parasiticide and skin antiseptic for animals. Poisoning has been associated with the use of the ointment in dogs (10). In human medicine the incidence of intoxication from ammoniated mercury ointment is regarded as being sufficiently high to condemn its use (5). Harvey (7) described apparent inorganic mercury poisoning in animals treated for ringworm. Ammoniated mercury was not incriminated in these cases. Paresis was the major presenting sign and there was an absence of other manifestations. Chronic intoxication in humans is a well documented result of industrial exposure to inorganic mercury (11). The classical signs include tremor and psychological disturbances. The nervous signs seen in this episode of inorganic mercury poisoning closely resembles those described for organic mercury poisoning. Motor incoordination giving the appearance of muscular weakness, tremor, reluctance of animals to stand and paresis are typically seen in organic mercury poisoning in cattle (2, 8). Skin lesions are frequently seen with elemental mercury poisoning (12) and less often in organic mercury toxicosis (4, 13). In these cases, the presence of numerous ringworm lesions, and the use of a steel comb to scarify these lesions prior to the application of ammoniated mercury ointment, made it difficult to assess the degree of dermal change attributable to mercury toxicosis. The distinctive punctate perianal lesions were not related to sites of application of the ointment. Similar punctate eruptions and vesicle formation have been described in human hypersensitivity reactions to inorganic mercurial ointments (5). The pustular lesions were similar to those described in metallic poisoning (12). Presumably, skin irritation developed slowly following the application of the ointment as mercury was ionized in the tissues (1). Oral lesions are associated with acute mercury toxicity but do not appear to be a frequent finding in chronic mercury poisoning in cattle. Reinders (12) reports oral erosions in one of a large number of cows showing signs following the ingestion of metallic mercury. The occurrence of oral lesions in two of the five cases described here seems to be a high incidence. 263
Respiratory system involvement is often poisoning. Bronchitis and bronchopneumonia were reported in an outbreak of metallic mercury poisoning (12). Japanese workers (4, 13) record bronchial catarrh as a characteristic finding in organic
seen in chronic mercury
mercury toxicosis. The absence of characteristic clinicopathological findings and gross postmortem lesions is typical of chronic mercury poisoning. Degeneration of the tunica media of arterioles of the brain and particularly of leptomeningeal vessels of the spinal cord are characteristic findings in mercury poisoning (9). The degeneration of the Purkinje network of the heart seen in the second postmortem is also a consistent finding in mercury poisoning. Generally, there is neuronal degeneration but this was not observed in these cases. Other investigators (4, 8) recorded individual differences among cattle and their response to mercury intoxication. There was a poor correlation between the severity of clinical signs and kidney mercury levels in this outbreak of poisoning. The kidney mercury levels in the experimental steer indicate ready absorption of ammoniated mercury following cutaneous application and ingestion. There was a rapid fall in kidney mercury levels in this animal following its removal from mercury exposure. Kidney mercury levels do not appear to fall as rapidly following organic mercury poisoning in humans (6). Suimmary Deaths occurred in cattle treated for ringworm with an ointment containing ammoniated mercury (3.8% mercury). The clinical signs observed were a gradual loss of body condition, ataxia and paresis. Affected animals exhibited pustular skin lesions, erosions of the oral mucosae and pneumonia. Pulmonary congestion and ecchymotic and paintbrush hemorrhages on the epicardium and endocardium were seen at necropsy. Histopathological changes were observed in blood vessels of the brain and spinal cord and in the Purkinje cells and myocardium of the heart. An animal experimentally treated with the same ointment exhibited no clinical signs but had kidney mercury levels comparable to the poisoned animals.
Re"sumie Des bovins sont morts a la suite d'un traitement de la teigne avec un onguent qui contenait du mercure precipite blanc (3.8% de mercure). Les signes cliniques se traduisirent
CANADIAN VETERINARY JOURNAL
par une perte graduelle de condition, de l'ataxie et de la paresie. Les animaux malades presentaient des pustules cutanees, des erosions de la muqueuse buccale et de la pneumonie. Lors de la necropsie, on observa de la congestion pulmonaire, des ecchymoses et des hemorragies "en coup de pinceau" sur l'epicarde, ainsi que sur l'endocarde. L'histopathologie revela la presence de lesions dans les vaisseaux sanguins du cerveau et de la moelle epiniere, ainsi que dans les fibres musculaires et les cellules de Purkinje du cceur. Le traitement experimental d'un bouvillon avec cet onguent ne provoqua pas de signes cliniques; la quantite de mercure qu'on recouvra de ses reins s'avera cependant comparable 'a celle des memes organes des sujets empoisonnes. Acknowledgments We wish to express our appreciation to Drs. R. B. Miller, P. B. Little and G. W. Thomson of the Department of Pathology, University of Guelph, who performed the necropsies, and to Mr. H. Funnell, Veterinary Services, O.M.A.F. who performed the toxicological analyses. References 1. BIDSTRUP, P. L. Toxicity of Mercury and its Compounds. London, England: Elsevier Publishing Company. 1964. 2. BOLEY, L. E., C. C. MORRILL and R. GRAHAmI. Evidence of mercury poisoning in
feeder calves, North American Vet. 22: 161164. 1941. 3. DUN, F. Veterinary Medicines - Their Actions and Uses. New York: William R. Jenkins. 1883. 4. FUJIMOTO, Y., K. OMSMMA, H. SATOH and Y. OHTA. Pathological studies on poisoning in cattle. Jap. J. vet. Res. 4: 17-32. 1956. 5. GOODMAN, L. S. and A. GLMAN. The Pharmacological Basis of Therapeutics, Fourth Edition. New York: The Macmillan Company. 1970. 6. HARTUNG, R. and B. D. DnMAN. Environmental Mercury Contamination. Ann Arbor, Michigan: Ann Arbor Science Publishing Co. 1972. 7. HARVEY, F. T. Mercurialism in cattle. Vet. Rec. 12: 328-329. 1932. 8. HERINGSTAD, R. R., C. K. W murET Am, B. BEYER, 0. MICKELSEN and M. J. ZABIK. Chronic methylmercury toxicosis in calves. J. Am. vet. med. Ass. 160: 173-182. 1972.
9. JUBB, K. V. J. and P. C. KENNEDY. Pathology of Domestic Animals, Second Edition. London, England: Academic Press. 1970. 10. LANDER, G. D. Veterinary Toxicology. London, England: Bailliere, Tindall and Cox.
1912. 11. MILLER, M. W. and T. W. CLARESON. Mercury, Mercurials and Mercaptans. Springfield, Illinois: Charles C. Thomas. 1973. 12. REINDERS, J. S. Mercury poisoning in cattle. Neth. J. vet. Sci. 4: 79-84. 1972. 13. SONODA, M., R. NAKAMURA, K. Too, A. MATSUHASHI, H. ISHIMOTO, R. SASAKI, K. ISHIDA and M. TAKAHASHI. Clinical studies on mercury poisoning in cattle. Jap. J. vet. Res. 4: 5-16.1956.
ANALYSE DE VOLUME Vertebrate Hard Tissues. L. B. Halstead. Pu- donne une liste de ref6rences bibliographiques blie par Springer Verlag, New York. 1974. plus approfondies et l'autre une classification 180 pages. Prix $7.80. taxonomique simplifiee des vertebres. Les dessins et les schemas sont bons, parfois excelCe petit ouvrage tente, de fa,on d'ailleurs lents. Les photographies sont egalement tres fort heureuse, de realiser une synthese des bonnes, de facon g6nerale. Certaines figures connaissances sur les tissus les plus durs des (13.2, par exemple) ne sont toutefois pas tres vertebres. L'enjeu, s'il est valable, est d'enver- suggestives; d'autres (13.3) tres conventiongure. Int6grer, dans un meme texte, des aspects nelles et classiques; certaines (13.5) tres d6aussi divers que la biochimie, la morphologie monstratives et vraiment nouvelles. Comme descriptive et surtout comparee, la pathologie, dans toute premiere edition, il existe quelques des notions de pal6ontologie et d'evolution au erreurs typographiques mineures (ex.: pterysens darwinien comme au sens ontog6nique goideus dans la fig. 17.2). du terme, constitue une entreprise extremeEn conclusion, ce petit livre constitue une ment difficile. Forcement, certains aspects de bonne synthese d'un sujet extremement vaste la matiere doivent rester dans l'ombre. et il atteint certainement le but que l'auteur Le livre est divise en trois parties: aspects s'etait fixe: "I hope this book will encourage mol6culaires et cellulaires, les tissus et, finale- students to delve deeper or even eventually to ment le squelette. La matiere est repartie en- enter the expanding field of calcified tissue tre 21 chapitres et deux appendices dont l'un research." J. Pi4rard. 264
