Trace elements in the human body HAMILTON
S M I T H , P H . D . , B.SC., A.R.I.C.
Dept. of Forensic Medicine, Glasgow University
I N T RODUCTIOI~
Trace elements in the human subject m a y be divided into two groups: those which are essential to normal human metabolism and those which are present only as contaminants. Unfortunately the present state of knowledge covers only a few elements. The method of showing that an element is essential is to find some mechanism in which it is involved, but we have made studies on As, Sb, Cu, Zn, Mn, Cd and Se recently which show that it is possible to differentiate the two groups by a statistical method. I f an element takes part in any biochemical function its uptake and release must be controlled. A control mechanism means t h a t a particular concentration level must be maintained. The result of this is t h a t in any random sample of the population the concentration distribution will be normal, i.e. the median and mean will coincide and 67 per cent of the samples will be within -4- one standard deviation. I f the element level is not maintained the distribution will be asymmetric with most of a random population having low values and a small number having relatively high ones depending on the exposure suffered in any given environment. The asymmetric distribution is probably log normal, i.e. if the logarithms of the values are used to plot the distribution, instead of the actual values, the distribution is normal. Fig. 1 shows the distribution of essential trace elements in heart and Fig. 2 shows the distribution of the non-essential trace elements. :Both sets of diagrams are constructed on similar base divisions so that a more easy comparison can be made. As can be seen asymmetric distribution of the non-essential trace elements is marked. Of the three non-essential trace elements shown, only one--mercury--is in concentrations comparable with those of the essential elements and this has been selected for further study. MERCURY
Mercury is listed as being the 62nd element in order of abundance in the earth's crust and has an average concentration of about 0.5 ppm, i.e. about a tenth that of arsenic; yet in man it has an average value of 1 ppm and therefore can be listed about 20th in order of concentration in the human body, i.e. somewhere between manganese and copper. This situation m a y well be due to a contaminated environment and in fact though very few would admit exposure to mercury it appears to be fairly widespread. The sources of contamination are not restricted to any one occupation. Mercury is used extensively in agriculture, industry and dentistry, with other contributions from laboratories, schools and similar places. A paper read to t h e British Homceopathic Congress, Glasgow, 31 August 1967
TRACE
ELEMENTS
IN THE HUMAN
97
BODY
80-
Cu
40.
ILl
0
Se
Mn
Zn
l m
!
10
0
20
3'0 0
1
2
2
Concentration
I0 0 200 '
'
(ppm)
Fig. 1. E s s e n t i a l t r a c e e l e m e n t s in d r y h e a r t .
80-
40-
J
t
00.1
0
I
3
6
0,3
0.6
Concentration (ppm) Fig. 2. N o n - e s s e n t i a l t r a c e e l e m e n t s in d r y h e a r t .
I t might easily be argued t h a t m a n y of the people most involved have been working for extensive periods in slightly contaminated environments without any apparent harm. However, this is not entirely true and though the usual poisoning reactions are absent m a n y minor disorders m a y possibly be traced to this source. I have selected the following investigations to demonstrate some of the points under consideration.
1 GeneralSurvey The samples of this survey of " n o r m a l " tissue were t a k e n during post-mortem examination from healthy subjects who had died as a result of violence. The subjects had lived and worked in the Glasgow area and as such m a y not be representative of the country as a whole. 3A
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TABLE I
Mercury (ppm) in dry tissue Tissue Adrenal Aorta Blood (whole)
No. of samples Maximum 18 23 3
Bone
16
Brain
21
Breast
2- 44 7.30 0.12 1.04
15-2
3
2.48
Hair (head) Hair (pubic) Heart Kidney Liver Lung Muscle (pectoral) Nail (finger) Nail (too) Ovary
70 22 22 20 22 21 15 25 22 10
24-4 5- 43 5.62 79.3 20.0 10.5 3- 40 33- 8 5.00 13.5
Pancreas
26
7.23
Prostate Skin Spleen Stomach Teeth Thymus Thyroid Uterus Urine*
5 18 21 21 59 3 24 11 46
1.53 18.7 7.41 13.3 18.1 8.90 24.6 4- 31 0-133
Minimum
Median
Mean
0" 15 0" 10 0-06 0.03 0.12 0.68 0.03 0.28 0.14 0-08 0.15 O. 30 O. 04 0" 80 0" 05 0"06 0.03 0.04 0-25 0-10 0- 06 0.14 0" 47 0.10 0-13 0-00097
0" 51 O. 90 0.12 0.30 1.07 -4.20 1.21 0.89 1- 51 1-40 1-33 O. 29 4.76 2- 75 0-73 0.72 0.53 2-00 0- 68 0" 89 2.13 -1- 07 0- 87 0.013
0" 80 1.39 0-09 0- 45 2.94 1.79 5-52 1- 62 1.76 9.03 3 -66 2- 55 O. 71 7.27 2.40 2" 14 1.14 0.65 3.34 1.50 2-27 3.22 4.75 3- 38 1-43 0-023
* Values for u r i n e are in ~g./ml.
The results given in Table I show t h a t the d i s t r i b u t i o n s are characteristic of a non-essential trace element. T h e y also show t h a t some people are exposed to a m u c h greater e x t e n t t h a n others, t h o u g h n o n e h a d a n y known exposure to m e r c u r y other t h a n i n d e n t a l repairs. I t is possible t h a t d e n t a l repairs m a y be t h e cause of t h e higher values f o u n d i n the k i d n e y samples, as k i d n e y does a p p e a r to concentrate m e r c u r y to some extent. I n a single n o n - f a t a l dose it is f o u n d t h a t the k i d n e y will have a c o n c e n t r a t i o n i n excess of 40 times t h a t of e.g. heart, lung or brain. This a c c u m u l a t i o n of m e r c u r y reflects the accumulat i o n of c a d m i u m i n the kidney. This p h e n o m e n o n is n o t shown to a n y appreciable e x t e n t b y other non-essentiM trace elements, e.g. arsenic or a n t i m o n y , a n d m a y simply be a m a t t e r of r e p l a c e m e n t b y some chemical species of a similar type. T h e a c c u m u l a t i o n of m e r c u r y in the liver is n o t so m a r k e d as with other nonessential trace elements, nor is it so m a r k e d in lung. Generally the l y m p h nodes e x h i b i t a n increase i n non-essential trace element c o n c e n t r a t i o n which m a y be more t h a n t e n times t h a t of other tissues. This increase is p r o b a b l y due to c o n c e n t r a t i o n of airborne material. I t is possible t h a t m e r c u r y is washed from this due to its higher solubility i n b o d y fluids. The n o t i c e a b l y high concentrations shown b y the hair, nail a n d skin are certainly due to external c o n t a m i n a t i o n along with deposition i n the biological matrix. I t is n o t certain t h a t a n y of these three tissues actively c o n c e n t r a t e elements. I t is p r o b a b l y accidental inclusion in a tissue i n which no f u r t h e r exchange is possible. I t is interesting to n o t e a t this p o i n t t h a t some elements, originally present as a n external c o n t a m i n a n t , are as difficult to remove as the same e l e m e n t which was deposited i n t h e biological m a t r i x .
TRACE ELEMENTS IN THE HUMAN BODY
2
99
Mercury in Industry
Metallic m e r c u r y vaporizes readily at room temperature a n d has a saturated concentration at t h a t temperature of 10 m g . / m s. The stated safety threshold in the atmosphere is 0" 1 mg./m s. Thus the v a p o u r equilibrium at room temperature is m u c h greater t h a n the m a x i m u m allowable concentration. However, with good ventilation the risk can be reduced significantly. W h e t h e r this reduction can be enough is not easy to establish, nor does analysis prove to be of m u c h help. This is well illustrated in the case of police fingerprint officers. Fingerprint powder is a mixture of m e r c u r y and chalk (1 : 2 b y weight). I n use this powder is spread over wide areas and is certainly a good source of m e r c u r y v a p o u r and dust. T h o u g h first recommended for use in 1905 it was not until 1949 t h a t the first report of poisoning of officers was made. Then seven of thirty-two officers were found to be suffering from chronic m e r c u r y poisoning. F u r t h e r studies in 1951 showed abnormal m e r c u r y urine levels in experienced officers b u t no evidence of mercury poisoning. The high levels found could be reduced considerably b y more careful attention to clean working. A s t u d y based on clinical findings in 1952 could n o t definitely say t h a t there was evidence of poisoning b u t did list a n u m b e r of mild s y m p t o m s which m a y have been due to mercury. Recently an investigation of hair, nail and urine levels was made to determine if a n y significance could be attached to these and so form the basis of a screening test. I t was found t h a t hair and nail were of no value due to the possibility of external contamination even of b o d y hair and toe nail. Consideration of the urine figures, where external contamination is unlikely, shows t h a t all the higher values were found in the subjects with the greatest exposure. E v e n so, only one value (0. 215 ppm) was outside the normal range a n d this was found to have returned to normal in the sample t a k e n one m o n t h later, even t h o u g h the exposure was unchanged. I f this high value was omitted, the mean of the other values was 0 . 0 1 5 ppm, which is slightly lower t h a n t h a t of the r a n d o m population tested. This value, which is equivalent to an excretion of 28/~g./day, agrees well with t h a t of 21 /~g./day found in 1951 and t h a t of 32/zg./day found in 1946. A review of the literature showed t h a t high values (100-400/~g./day) indicated possible m e r c u r y poisoning, b u t t h e y were sometimes found when no s y m p t o m s were present. Alternatively low values (30-100 /~g./day) were sometimes associated with appreciable symptoms. I t appears, therefore, t h a t urine values must be interpreted with great caution a n d t h a t some people are v e r y m u c h more sensitive to m e r c u r y t h a n others. This sensitivity has been adequately demonstrated using p a t c h tests and in practice b y removing m e r c u r y fillings from teeth to clear up sensitive reactions. I n contrast to the fairly low values f o u n d for fingerprint officers, Table I I TABLE
II
Mercury in indu~triaUy exposed subjects Subject
Head hair (ppm)
Body hair (ppm)
1 2 3
98" 6 34" 6 45.5
208-0 60' 0 32.4
1 2 3
31.8 5" 1 2" 1
7.5 1" 9 1-2
Nail (ppm)
Urine (~g./ml)
1068-0 20.0 13-1
0" 36 0- 024 0-015
Before laboratory clean up
O"12 0" 005 0"001
Three months
25.0 6" 7 0" 47
Remarks
after
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shows the values found in samples taken from subjects working in a commercial laboratory. I t will be seen that exposure is high and the subject most exposed is excreting remarkable amounts of mercury in the urine even three months after the exposure was reduced. The most notable fact, however, is that none of the subjects showed any symptoms of mercury poisoning.
3
Mercury in Dental Practice
I t has been shown that mercury in dental amalgams is a slight health hazard, at the time of insertion or removal, to both patient and dentist. However, having noticed a certain careless approach to the use of mercury by some dental workers it was felt that the hazard might not be so restricted in time or intensity. The method of choice in the preparation of silver amalgam is to place the mixed amalgam in a dental napkin and wring out the excess mercury with the fingers. I t is not unknown for this excess mercury to be flicked on to the floor. A group of female assistants, who had worked continuously in a surgery for more than two years, was selected. A further group of the same age, but with no known exposure to mercury, was also chosen. Samples of hair and nail were analysed and on comparison gave results indicating moderate contamination of the exposed group with levels well above those found in e.g. fingerprint officers. On analysis of hair and nail from one dentist values of 171 and 558 ppm respectively were obtained. His assistant showed similar levels. Further inquiry found them both complaining of salivation, tremors, insomnia and character change, all typical of chronic mercury poisoning. I t was soon discovered that mercury from the preparation of amalgams escaped on to the floor near a convector heater. Under the floorboards 3 ml. of mercury was found. I t is noticeable that though some other assistants had levels approaching those of the case quoted none of them had any obvious symptoms of poisoning.
4
Accidental Exposure in the Home
A schoolboy took about 200 g. of mercury from school to his home where he played with it. The result was a fair distribution over the living room carpet. This hazard was intensified by the resulting vigorous dispersal by means of an electric vacuum cleaner. The impossibility of adequately cleaning up this amount of metal without expert help is obvious. I t was not surprising, therefore, that all members of the household should succumb to mercury intoxication some time later. The symptoms reported included tremors, exfoliation and in one T A B L :E I I I
Mercury ( ppm) in t~sue~ of exposed family Hair S ubject Father Son Mother
Head
Pubic
6.89
4.05
17.5 141.0
131.0 6.35
Nail Skin Blood U r i n e Saliva Toe F i n g e r E x f o l i a t e d N o r m a l (dry)
Remarks
51.5
36.4
20.9
11.3
3.38 0.58
0.42 0.71
0'027
Before treatment Recurrence at 2 months
71-7
--
156.0
92-5
3.92 0.52
3.74 0.76
0.009
Before treatment Recurrence at 2 months
35.1
20.2
--
--
2.16 0.35
0.1O 0.56
0.008
Before treatment No symptoms at 2 months
Daughter
8.29
--
53.1
B a b y (male)
8-36
--
138.0
Random Sample
5-52
1.62
2.40
3.6
--
2.0
2-03
0.29
--
B e f o r e treatment
--
--
--
3.28
0.12
--
Before treatment
7.27
--
3.34 0.09
0.023
--
Table I
TRACE
ELEMENTS
IN
THE
HUMAN
BODY
101
case, hallucinations. The diagnosis of mercury poisoning was supported b y the mercury content of some tissues t a k e n before treatment (Table I I I ) in comparison with normal values. I t is likely, however, t h a t some degree of external contamination was present. The most remarkable point about the case was the range of symptoms shown by the different subjects. These varied from hallucinations and other marked symptoms in the eldest son to very slight effects indeed in the case of the young daughter and baby. Two months after the first exposure the father and son had a recurrence of symptoms which they claimed was due to inadequate cleaning of the house which m a y quite well be true. The mother who was sampled at the time showed similar blood and urine levels but she was quite free of symptoms. Conclusions Mercury is a widely distributed and to some extent unrecognized health hazard. The extreme variability of reaction to it exhibited by the various subjects together with its occurrence in relatively large amounts within the body m a y well lead to mild unrecognized symptoms in some subjects. On the other hand slight overexposure while leading to violent reactions in some individuMs m a y well cause no effects in others. Analysis of samples is of some use in estimating exposure but requires careful assessment. The general feeling at the moment is t h a t mercury levels canaot be accurately equated to seriousness of symptoms and t h a t clinical observation is a more important factor once the possible presence of mercury has been established.
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