Food Additives & Contaminants

ISSN: 0265-203X (Print) (Online) Journal homepage: http://www.tandfonline.com/loi/tfac19

The importance of endogenous histamine relative to dietary histamine in the aetiology of scombrotoxicosis P. Ijomah , M. N. Clifford , R. Walker , J. Wright , R. Hardy & C. K. Murray To cite this article: P. Ijomah , M. N. Clifford , R. Walker , J. Wright , R. Hardy & C. K. Murray (1991) The importance of endogenous histamine relative to dietary histamine in the aetiology of scombrotoxicosis, Food Additives & Contaminants, 8:4, 531-542, DOI: 10.1080/02652039109374005 To link to this article: http://dx.doi.org/10.1080/02652039109374005

Published online: 10 Jan 2009.

Submit your article to this journal

Article views: 10

View related articles

Citing articles: 5 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: 18:10

FOOD ADDITIVES AND CONTAMINANTS, 1991, VOL. 8, NO. 4, 5 3 1 - 5 4 2

The importance of endogenous histamine relative to dietary histamine in the aetiology of scombrotoxicosis P. IJOMAH†, M. N. CLIFFORD†, R. WALKERt, J. WRIGHT†, R. HARDY ‡ and C. K. MURRAY ‡ † School of Biological Sciences, Food Safety Research Group, University of Surrey, Guildford GU2 5XH, UK; ‡ Ministry of Agriculture, Fisheries and Food, Torry Research Station, PO Box 31, 139, Abbey Road, Aberdeen AB9 8DG, UK

Downloaded by [Universite Laval] at 18:10 05 November 2015

(Received 15 January 1991, revised 29 May 1991) Deliberately spoiled mackerel samples and mackerel samples implicated in outbreaks of scombrotoxicosis were, under medical supervision, tested blind on normal, healthy volunteers of both sexes. These experiments identified batches of fish which could induce nausea/vomiting and/or diarrhoea when 50 g samples were consumed. It was also established that the fillets in a batch were neither of equal potency nor homogeneous with respect to histamine content. Strong evidence was obtained that dietary histamine is not a major determinant of scombrotoxicosis since potency was not positively correlated with the dose, and volunteers appeared to fall into susceptible and non-susceptible subgroups. However, there is no reason to suspect allergy as being solely responsible for these differences in sensitivity. It is also possible to discount body weight as a factor. While the data suggest that females may be more susceptible than males, this effect cannot be confirmed at the present time. Studies with susceptible volunteers predosed with either placebo or H1 antagonist (chlorpheniramine 4 mg) demonstrated convincingly that the antihistamine can abolish vomiting and diarrhoea associated with the ingestion of 50 g of scombrotoxic fish. It is therefore postulated that endogenous histamine released by mast cell degranulation has a significant role in the aetiology of scombrotoxicosis, whereas the role of dietary histamine is minor. The nature and origin of the agent responsible for mast cell degranulation is being investigated. Keywords: scombrotoxicosis, mackerel, histamine, Scombridae, Scomberosocidae

Introduction

Scombrotoxicosis is generally associated with ingestion of fish from the families Scombridae and Scomberosocidae. These include mackerel, tuna, saury, bonito, seerfish and butterfly kingfish. The symptoms of scombrotoxicosis include flushing, headache, cardiac palpitation, dizziness, itching, burning of mouth and throat, rapid and weak pulse, rashes on face and neck, swelling of face and tongue, abdominal cramp, nausea, vomiting and diarrhoea. It is unusual for all of these symptoms to be recorded on any one occasion, but the occurrence of several of these symptoms shortly after the consumption of scombroid fish would be the normal diagnostic criterion for scombrotoxicosis. Scombrotoxicosis has also been associated with the consumption of nonscombroid fish such as sardines, pilchards, anchovies, herring and marlin. Although the possibility of some misdiagnoses cannot be ruled out, the feature 0265-203X/91 $3.00 © 1991 Taylor & Francis Ltd.

Downloaded by [Universite Laval] at 18:10 05 November 2015

532

P. Ijomah et al.

common to all of these fish is a high muscle histidine content. During spoilage this histidine undergoes bacterial decarboxylation to histamíne (Taylor et al. 1978). Since in many cases comparatively high levels of histamíne (e.g. in excess of 1 g per kg) have been detected in remnants of food implicated in outbreaks of scombrotoxicosis, and since the symptoms of this poisoning could be alleviated with antihistamines, it has been suggested, even comparatively recently, that dietary histamíne is the causative agent and that the condition should be called 'histamíne poisoning* (Taylor 1985, 1986). Although earlier there was evidence that histamíne poisoning could occur when clearance is impeded, for example by monoamine oxidase inhibitors (Uragoda and Kottegoda 1977, Uragoda and Lodha 1979), Arnold and Brown (1978) have questioned whether it can be the sole scombrotoxin since it is efficiently metabolized in the normal human gut and not absorbed per se. Others have reported elevated urinary histamíne and JV-methylhistamine following scombrotoxicosis associated with the consumption of marlin and remain convinced that dietary histamíne is the causative agent (Hughes and Potter 1991, Morrow etal. 1991). However, in the years 1976-1986, over half the reported incidents of scombrotoxicosis were associated with histamíne concentrations below 50 mg per kg (Bartholomew etal. 1987), levels too low to account for the severity of the symptoms observed, and again suggesting that histamíne is not the sole causative agent. In such situations it must be recognized that 'plate-waste' has rarely been available, and that the fish analysed may not have been identical to the fish consumed. Indeed, the grossly variable histamíne content of individual fillets, in batches thought to be closely associated with an incident of scombrotoxicosis, has recently been reported (Ijomah etal. 1989, 1991). The extreme values were 440-2800 mg per kg. Much more difficult to rationalize and discount, however, are reports from well controlled volunteer studies in which high levels of histamíne failed to elicit any significant response. For example, Clifford et al. (1989) reported only occasional mild perioral tingling after administration of portions of fresh mackerel to which 300 mg of histamíne had been added. Such additions raised the histamíne content to more that 6000 mg per kg, grossly in excess of levels found in some fish associated with scombrotoxicosis, and the absence of gastrointestinal and systemic symptoms is consistent with efficient detoxification as claimed by Arnold and Brown (1978). These anomalies in the dose-response relationship led to the conclusion (Clifford et al. 1989) that dietary histamíne cannot be the sole causative agent of scombrointoxication. The present investigation was designed to clarify whether dietary histamíne is only coincidentally implicated, or whether it has any causative (additive or synergistic) involvement in the production of the more severe symptoms associated with scombrotoxicosis. Experimental

General The protocol employed was approved by the South West Surrey District Health Authority Ethics Committee, and was similar to that used in our previous studies (Clifford etal. 1989, Ijomah etal. 1989, 1991). The mackerel samples described below were served with toast and tea ad libitum or with a glass of orange juice

Downloaded by [Universite Laval] at 18:10 05 November 2015

Aetiology of scombrotoxicosis

533

(Experiment 3) to medically screened, informed volunteers accommodated in the Clinical Investigation Unit at St Luke's Hospital (Guildford, UK). For each subject, body weight was recorded, and blood group and circulating IgE levels were determined. Only one subject had a history of allergy, but not to mackerel so far as is known. Subjects were asked to complete a questionnaire at specified intervals for a period of 48 h and to record the occurrence of the following subjective symptoms: headache; flushing; oral tingling; visual disturbance; abdominal pain; nausea; palpitation; wheeziness; diarrhoea; flatulence; shivering and any other symptoms (miscellaneous). Individual symptoms were recorded on a scale of 1 to 3, with 3 being the most intense. Recording of subjective symptoms commenced 10 min prior to eating the fish. In all studies, onset within 6 h (in practice usually within 2-3 h) of vomiting and/or diarrhoea was taken as a positive response, i.e. as evidence of scombrotoxicosis. This diagnostic criterion was chosen to eliminate false positives since doses of histamíne much greater than those associated with the mackerel samples had previously been shown not to produce these symptoms (Clifford et al. 1989) and the absence of other microbial toxins had been established by prior screening of the fish. While lesser, purely subjective symptoms may have been a response to scombrotoxin(s), they may also have been a response to histamíne in the sample or even a response to the stress associated with the situation. The consequent risk of some false negative diagnoses and hence under-recording of scombrointoxication was considered tolerable. To maximize sample homogeneity, the fish samples used in Experiment 1 were prepared by mincing fillets obtained from several fish. In Experiments 2 and 3, to avoid the possibility of diluting scombrotoxic material with non-toxic material, individual fillets were quartered and the samples presented were prepared from the diagonally opposed quarters of a single fillet. The authenticity of the volunteers' responses was randomly checked by re-presentation of some samples at some point over the experimental period. An interval of at least two weeks was allowed between the first and the second presentation. Precisely weighed samples of approximately 50 or 100 g were normally used. Any fish not consumed, for whatever reason, was collected and weighed so that the precise dose was known. Experiment 1. This experiment was an attempt to ascertain whether scombrotoxic samples could be produced when sound whole mackerel was allowed to spoil at ambient temperature on the floor of a fish processing area prior to smoking. These samples were prepared from commercial landings by the Ministry of Agriculture, Fisheries and Food (Torry Research Station) and delivered frozen to the University of Surrey. The samples were stored in a freezer at -20°C and thawed immediately before use by placement overnight in a refrigerator at 4°C. The histamíne contents were: Batch 1, control, 5 mg per kg; Batch 2, good quality, 68 mg per kg; Batch 3, spoiled, 230 mg per kg; Batch 4, more extensively spoiled, 400 mg per kg; and Batch 5, associated with an episode of scombrotoxicosis in Coventry, 2160 mg per kg. The samples were shown to be free from known microbial pathogens and

534

P. Ijomah et al.

Downloaded by [Universite Laval] at 18:10 05 November 2015

toxins prior to their testing on nine volunteers, who on different occasions, were fed 50 g of each of the fish samples, using a randomized single blind protocol. Selected volunteers were in addition given 100 g (double dose) of Batches 3 and 4. Some volunteers were also given 50 or 100 g of Batch 4 spiked with 130 mg of histamíne (as histamíne dihydrochloride; Sigma H-7250), which was incorporated as described previously (Clifford et al. 1989). Experiment 2. Smoked mackerel fillets, associated with an incident of scombrotoxicosis which occurred on a North Sea oil rig, or material seized from suppliers' cold stores in north-east Scotland, and which was thought to be of the same biological origin and similar but unknown history, were tested on 26 volunteers (15 males and 11 females). This suspect material was for convenience subdivided into nine coded batches (6-14) depending upon where it was seized. Samples (50 g) prepared from opposite quarters of a given fillet were presented to each volunteer on each study occasion. In order to ascertain the variation in the histamíne content, each fillet was analysed for histamíne content as described by Taylor et al. (1978). Where fillet size permitted, two matched samples were prepared from the same fillet by pooling opposite quarters so as to minimize as far as possible differences in composition that might complicate interpretation of the subjects' responses. These matched samples were presented blind, either to the same volunteer on two different occasions, or to two different volunteers. Some of the early results from this experiment were presented at the Torry Jubilee Conference (Ijomah et al. 1989, 1991). Experiment3. In this study the effect of pretreatment with antihistamine on volunteers' responses to suspect fish was examined. Six volunteers (three males and three females) who had on at least one occasion given a positive response (vomiting and/or diarrhoea) to suspect fish were selected for this study. Two 50 g samples were prepared from diagonal quarters of each fillet and in paired studies presented blind to the volunteers with and without antihistamine. The antihistamine (chorpheniramine, 4 mg, suspended in syrup) or placebo (syrup BP) were administered 25 min prior to presenting the fish. Results and discussion

Data generated in the three experiments have, where appropriate, been pooled so as to facilitate comparison. In this paper the test outcome has been defined as positive scombrotoxicosis if the volunteer reported vomiting and/or diarrhoea. Mild symptoms such as headache, perioral tingling, flushing, nausea and flatulence, either alone, or in some combination, have been considered as equivocal and treated as negative. As stated earlier, it is possible that the use of this strict criterion has led to an under-estimation of the incidence of scombrotoxicosis, but this is considered to be preferable to mis-diagnosis and over-estimation. For the first time in our investigation of the aetiology of scombrotoxicosis, spanning eight years, and possibly for the first time in the history of the phenomenon, it has been possible under controlled conditions to induce in volunteers the more extreme symptoms considered to be indicative of scombrotoxicosis.

Downloaded by [Universite Laval] at 18:10 05 November 2015

Aetiology of scombrotoxicosis

535

Table 1 records the histamíne contents of 14 batches of fish, their ability to induce a positive response in volunteers, and the doses of histamíne associated therewith. As previously reported (Ijomah et al. 1989, 1991), it is clear that the fish in a batch can differ considerably (by up to six times) in their histamíne content. It is also clear that the batches of fish differ in their ability to induce positive responses. Column 5 in table 1 records the number of positive outcomes expressed as a percentage of the number of volunteers used to test that batch of fish. Values range from 0 to 42%. However, since some volunteers have never given a positive response, the possibility cannot be discounted that some people are relatively insensitive. Therefore, column 6 records the corresponding percentage after recalculation for only those volunteers proven to be susceptible by presenting at least one positive response. Values now range from 0 to 100% overall, and from 25 to 100% for Batches 5-14 thought to be associated with scombrotoxic incidents. The range of histamíne doses (mg per kg body weight) are given, separately for males and females, for both positive and negative outcomes (columns 9-12). The lowest dose of histamíne associated with a positive outcome to spoiled fish (irrespective of whether this was 'natural' or 'induced' spoilage) was 0-3 mg per kg body weight, whereas the highest dose not giving a positive outcome in a volunteer proven to be susceptible was almost ten times this figure at 2-8mg per kg. Similarly, previous studies using sound fish spiked with histamíne to give doses of some 3-4 mg per kg body weight produced only mild subjective symptoms such as perioral tingling (Clifford etal. 1989, Ijomah etal. 1989, 1991). These data for histamíne dosage approximate to the inverse of a typical doseresponse relationship and strongly suggest that histamíne perse is not the scombrotoxin responsible for the vomiting and/or diarrhoea; some other toxin or potentiator must be involved. In this regard, the data for Batch 4 are particularly interesting, since feeding 100 g of minced mackerel caused vomiting and/or diarrhoea in three out of the four susceptible volunteers challenged, whereas feeding 50 g, or 50 g with added histamíne (130 mg), affected only one or two of the four, respectively. Assuming that these minced samples were truly homogeneous, it would appear that doubling the dose of both the histamíne and the unknown scombrotoxin(s) was more effective in inducing vomiting and/or diarrhoea than increasing the histamíne dose 7·5 fold at constant scombrotoxin(s) dose. This observation could be taken as evidence for thé potentiation of histamíne toxicity, but the relatively small number of replicate observations limits the reliability of such an interpretation, although in studies with guinea pigs, Bjeldanes et al. (1978) have shown the potentiation of histamíne by cadaverine. While such synergy cannot be unequivocally eliminated at the present time, this possibility will not be further discussed in this paper, because preliminary data for the contents of cadaverine and four other amines in these fish do not support such a mechanism. These data will be reported and discussed in a subsequent publication. The results obtained from the use of matched fillet samples are presented in tables 2 and 3. Once a scombrotoxic sample had been identified, the volunteer to receive the second half was selected so as to investigate either consistency of response (table 2) or the effect of inter-individual differences such as body weight and sex. Table 3 also shows whether previous failure to respond was due to exposure only to non-scombrotoxic samples.

Table 1. Volunteer responses to mackerel samples. Positive responses % of Number of volunteers Batch number

Total K

allU

sample size

Susceptible

Histamíne content of fish mg per kg fresh weight

volunteers

volunteers C/B X 100

Mean

9 8

4 4

0 0

0 0

0 0

5d 68d

3(50g)

9

4

0

0

0

230"

4(50g)

9

4

1

11

25

400 d

9

Male volunteers

O

4

3

33

75

400 d

Range

9 9

§• c

Responding* Non-respondingc Responding1" Non-responding

no response no response (1 person) no response (1 person) no response (2 people)

0-002-0-004 0-03-0-05

no response no response

0-004-0-010 0-05-0-06

0-1-0-2

no response

0-18-0-22

0-2-0-3

0-3

0-3-0-4

0-6

0-4-0-5

(1 person) 0-6-0-8

0-7

(2 people) 4 (50 g plus 130 mg histamíne) 5 (50 g)

3

Female volunteers

« f^\ f i m « 4 1 A ^ f* C*

O

Total Susceptible" Responding b C/A x 100

l(50g) 2(50g)

4 (100 g)

Histamíne dose mg per kg body \veight

4 4

2 1

22 11

50 25

3000"

2-2

2160d

(1 person) no response (1 person)

1-4-2-1

2-4

2-5-2-8

(1 person) 1-03-1-48

0-7

(1 person)

1-8-2-04

;t al.

Downloaded by [Universite Laval] at 18:10 05 November 2015

ON

19 21

6 7

6 5

32 24

100 1\

1406 1505

480-2800 540-2000

1-1-2-1 0-4-1-4

0-6-1-8 0-4-1-9

8 (50 g) 9 (50 g)

17 16

6 6

4 2

24 13

67 33

1228 1509

440-2660 1060-2160

0-3-1-9 0-4-1-7

10 (50 g)

10

4

1

10

25

1422

600-1960

Π (50 g)

7

3

1

14

33

1147

740-1980

12 (50 g)

8

4

3

38

75

1290

340-1800

13 (50 g)

9

3

1

11

33

1470

1280-1740

14 (50 g)

7

5

3

42

60

1933

1700-1940

0-6-1-2 0-8 (1 person) no response (1 person) 1-5 (1 person) 1-3 (1 person) 0-8 (1 person) 0-7 (1 person)

0-4-1-5 0-8 (1 person) 1-5 (1 person) 0-9-1-7 0-7-1-7

0-4-1-6 1-7 (3 people) 0-7-0-8 1-3 (1 person) 1-3 (1 person) no response (1 person) 0-5-1-4

0-6-1-4 0-5-1-9

no response (1 person) 0-5-0-6 (2 people)

0-4-1-4

0-4-1-2 0-8-1-2 0-7-1-2 0-6-1-4 1-0-1-2 V

1-5 (1 person)

"Volunteers, , who on at least one ιoccasion during the study, suffered vomiting and/or diarrhoea when presented with a sample of fish. "Volunteers who suffered vomitinjI and/or diarrhoea when presented with fish from the batch specified. Dose not shown if symptoms of scombrotoxicosis not presented. c Volunteers who did not suffer vomiting and/or diarrhoea when presented with fish from the batch specified. d Samples made homogeneous by ιnincing.

δ' δ"

s. I «g

s

rtoxicosis

Downloaded by [Universite Laval] at 18:10 05 November 2015

6 (50 g) 7 (50 g)

538

P. Ijomah et al. Table 2. Reproducibility of volunteer response to a given mackerel sample. Symptoms

Downloaded by [Universite Laval] at 18:10 05 November 2015

Volunteers

Batch

1st Presentation

2nd Presentation

SD

Oral tingling Flushing Nausea Diarrhoea Flatulence

Oral tingling Flushing Diarrhoea Flatulence Headache Visual disturbance Nausea

AB

Oral tingling Headache Visual disturbance Light-headedness Numbness of cheeks and gums Nausea Flushing

Oral tingling Headache Visual disturbance Light-headedness Numbness of cheeks and gums

SD

12

Oral tingling Flushing Headache Nausea Diarrhoea Flatulence

Oral tingling Flushing Headache Nausea Diarrhoea Flatulence

JL

12

Oral tingling Flushing Nausea Flatulence Headache

Oral tingling Flushing Nausea Flatulence

Oral tingling Headache Visual disturbance Aching behind eyes Palpitation Breathlessness Tiredness

Oral tingling Headache Visual disturbance Aching behind eyes

AB

The data in table 2 show that blind re-presentation of a given sample to a given volunteer consistently resulted in similar symptoms being recorded. Discrepancies were mostly limited to a temporal displacement in the onset and termination of individual symptoms, and some variation in the subjective grading of their intensity, this latter being almost inevitable in the absence of an absolute standard against which comparison could be made. These very consistent duplicate observations thus suggest that the other volunteer data reported here can be considered as reliable. Paired studies in which 'identical' samples from the same fillet were given to two different volunteers (table 3) support the indications of data in table 1, that the volunteers can be divided into responding and non-responding subgroups.

Aetiology of scombrotoxicosis

539

Table 3. Studies using matched fillet pairs.

Downloaded by [Universite Laval] at 18:10 05 November 2015

Paired comparison No.

Batch

Histamíne consumed (mg)

1

6

140

KP (67) (m) Headache Flushing Diarrhoea

2

6

80

SD (64)(f) Oral tingling Headache Flushing

Nausea Flatulence Diarrhoea

FC (64)(m) Flushing Shivering Wheeziness

Flatulence Nausea Diarrhoea

3

6

4

7

7

5

6

7

74

99

110

100

Volunteers, body weight (kg), sexa and symptoms

NM (57) (f) Headache Stomach ache Nausea

Vomiting Diarrhoea

SD (64)(f) Oral tingling Flushing Headache

Nausea Diarrhoea

JL (60)(f) Oral tingling Flushing Headache

7

7

27

RM (57) (f) Flushing Wheeziness

8

9

76

SD (64)(f) Oral tingling Headache Flushing

9

13

1

m = male: f = female.

87

DC (89) (m) No symptoms

JW (60) (m) Headache Flushing Oral tingling Stomach ache

Flatulence Nausea

CM (57)(f) Oral tingling Nausea CD (52) (m) No symptoms

BJ (105)(m) No symptoms

CM (57) (f) No symptoms

SD (64) (f) Oral tingling Flushing Headache

Flatulence Nausea

KP (67) (m) Nausea Diarrhoea

Flatulence Nausea

NM (57) (f) Headache Diarrhoea Shivering Vomiting Nausea CD (52) (m) Headache

P. Ijomah et al.

Downloaded by [Universite Laval] at 18:10 05 November 2015

540

The lack of association between the IgE values and volunteer responses provides no evidence that the sensitivity has an allergic basis. Similarly, the fact that all of the susceptible volunteers have responded negatively on a subsequent occasion indicates that idiosyncratic intolerance is not a factor in these responses. Neither can these differences in response be linked simply with differences in body weight since in paired comparisons 2, 3, 5, and 7, the volunteer with the lighter body weight presented the milder symptoms. With regard to female volunteers the difference in sensitivity was confirmed using two different batches of fish (paired comparisons 2 and 5). Prior administration of antihistamine to three susceptible female volunteers (four test occasions) resulted in the suppression of all symptoms except flatulence (table 4). The efficacy of the antihistamine was very clearly indicated by its ability to abolish the most violent response yet observed in these investigations, and undoubtedly equivalent to those known anecdotally. (The subject (SD) only displayed mild flatulence on ingestion of a sample from Batch 10 (1 -7 g histamíne per kg) plus antihistamine. When the same sample was administered with placebo, she presented almost immediately with violent vomiting and rapidly thereafter with diarrhoea which required her detention in hospital for several hours (table 4).) Table 4. The effect of predosing with placebo and antihistamine on the response of susceptible volunteers to scombrotoxic mackerel.

Volunteer SD (F)

NM (F)

JL (F)

Batch of fish, drug treatment and quantity of histamíne consumed

Symptoms

7 + Placebo 61 mg histamíne

Headache Flushing Oral tingling Visual disturbance Nausea Flatulence

7 + Antihistamine 61 mg histamíne

Flatulence

14 + Placebo 33 mg histamíne

Headache Flatulence Diarrhoea Stomach ache

14 + Antihistamine 33 mg histamíne

Flatulence Stomach ache

14 + Placebo 28 mg histamíne

Headache Oral tingling Flatulence Nausea Diarrhoea

14 + Antihistamine 28 mg histamíne

Flatulence continued

Aetiology of scombrotoxicosis

541

Table 4. (Continued) SD (F)

10 + Placebo 85 mg histamíne

10 + Antihistamine 85 mg histamíne

Downloaded by [Universite Laval] at 18:10 05 November 2015

AS

(M)

AS (M)

JW (M)

KP (M)

13 +Placebo 64 mg histamíne

Headache Flushing Oral tingling Visual disturbance Shivering Flatulence Nausea Diarrhoea Vomiting Flatulence Nausea

13 + Antihistamine 64 mg histamíne

No symptoms

13 +Placebo •26 mg histamíne

Headache Oral tingling

13 + Antihistamine 26 mg histamíne

Headache Oral tingling

14 + Placebo 44 mg histamíne

Headache Oral tingling

14 + Antihistamine 44 mg histamíne

Headache Oral tingling Stomach ache

12 + Placebo 66 mg histamíne 12 + Antihistamine 66 mg histamíne

Headache Nausea No symptoms

Although two susceptible male volunteers participated (on three occasions in total) in this study they displayed only mild subjective symptoms when given fish with placebo. While these symptoms did not meet our criteria for positive scombrotoxicosis, they were abolished by the antihistamine, and these observations are thus consistent with those made on female volunteers. It is presumed that these failures to respond to the challenge are a reflection of between-fillet variability seen even in batches proven to be scombrotoxic. To summarize, these investigations have demonstrated that: 1. some samples of mackerel low in histamíne have in some volunteers elicited the symptoms (vomiting and/or diarrhoea) diagnostic for scombrotoxicosis, whereas exogenous histamíne, even in large doses (Clifford etal. 1989), has failed so to do; 2. pretreatment with an antihistamine prevented the vomiting and/or diarrhoea produced when susceptible volunteers ingested 50 g of scombrotoxic mackerel.

Downloaded by [Universite Laval] at 18:10 05 November 2015

542

P. Ijomah et al.

In addition, the results presented here are consistent with the suggestion (Ijomah etal. 1989, 1991) that there may be considerable inter-individual differences in susceptibility to the toxin(s). However, an alternative explanation might be that volunteers who failed to respond, did so because some fillets contained little or no toxin(s). The first observation indicates clearly that exogenous histamíne per se at the levels observed in this study is not responsible for the vomiting and/or diarrhoea, whereas the second, establishes a role for endogenous histamíne. Together, these observations indicate the occurrence of mast cell degranulation in the gastrointestinal tract, with the sequelae (vomiting and/or diarrhoea) being due primarily to the release of endogenous histamíne (and probably other biologically active substances) which induce contraction of the smooth muscle. The role of dietary histamíne in the aetiology of scombrotoxicosis is minor. The nature and origin of the substance(s) causing degranulation remain unknown, but their potency, indicated by the rapid onset of diarrhoea after almost immediate voiding of the stomach contents, cannot be doubted, since very little scombrotoxin(s) could have reached the lower GI tract under these circumstances. Acknowledgements

This study was supported financially by the Ministry of Agriculture, Fisheries and Food. The cooperation and fortitude of our volunteers is also gratefully acknowledged. References ARNOLD, S. H., and BROWN, W. D., 1978, Histamine (?) toxicity from fish products. Advances in Food Research, 24, 133-154. BARTHOLOMEW, Β. Α., BERRY, P. R., RODHOUSE, J. C., GILBERT, R. J., and MURRAY, C. K., 1987,

Scombrotoxic fish poisoning in Britain: features of over 250 suspected incidents from 1976 to 1986. Epidemiology and Infection, 99, 775-782. BJELDANES, L. F., SCHUTZ, D. E., and MORRIS, M. M., 1978, On the aetiology of scombroid poisoning:

cadaverine potentiation of histamine toxicity in the guinea pig. Food and Cosmetics Toxicology, 16, 157-159. CLIFFORD, M. N., WALKER, R., WRIGHT, J., HARDY, R., and MURRAY, C. K., 1989, Studies with

volunteers on the role of histamine in suspected scombrotoxicosis. Journal of the Science of Food and Agriculture, 47, 365-375. HUGHES, M. J., and POTTER, M. E., 1991, Scombroid fish poisoning: from pathogenesis to prevention. The New England Journal of Medicine, 324, 766-768. IJOMAH, P., CLIFFORD, M. N., WALKER, R., WRIGHT, J., HARDY, R., and MURRAY, C. K., 1989, Torry

Research Station: Diamond Jubilee Conference, Aberdeen, August 1989. Further volunteer studies on scombrotoxicosis. IJOMAH, P., CLIFFORD, M. N., WALKER, R., WRIGHT, J., HARDY, R., and MURRAY, C. K., 1991,

Further volunteer studies on scombrotoxicosis. Pelagic Fish: the resource and its exploitation. (Oxford: Fishing News Books) (in press). MORROW, J. D., MARGOLIS, G. R., ROWLAND, J., and ROBERTS, L. J., 1991, Evidence that histamine

is the causative toxin of scombroid fish poisoning. The New England Journal of Medicine, 324, 716-720. TAYLOR, S. L., 1985, Histamine poisoning associated with fish, cheese and other foods. (Geneva: WHO). TAYLOR, S. L., 1986, Histamine food poisoning: toxicology and clinical aspects. C.R.C. Critical Reviews of Toxicology, 17, 91-128. TAYLOR, S. L., LIEBER, E. R., and LEATHERWOOD, M., 1978, A simplified method of histamine analysis of food. Journal of Food Science, 43, 247-250. URAGODA, C. G., and KOTTEGODA, S. R., 1977, Adverse reactions to isoniazid on ingestion of fish with a high histamine content. Tubercle, 58, 83-89. URAGODA, C. G., and LODHA, S. C., 1979, Histamine intoxication in a tuberculosis patient after ingestion of cheese. Tubercle, 60, 59-61.

The importance of endogenous histamine relative to dietary histamine in the aetiology of scombrotoxicosis.

Deliberately spoiled mackerel samples and mackerel samples implicated in outbreaks of scombrotoxicosis were, under medical supervision, tested blind o...
867KB Sizes 0 Downloads 0 Views