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Sweat lead levels in persons with high blood lead levels: experimental elevation of blood lead by ingestion of lead chloride
The Science oi the Total Environment, 108 (1991) 235-242 Elsevier Science Publishers B.V., Amsterdam
235
Sweat lead levels in persons with high blood lead levels: experimental elevation of blood lead by ingestion of lead chloride Folashade O. Omokhodion a'* and Goeffrey W. Crockford b Unit of Occupational Health, London School of Hygiene and Tropical Medicine, Keppei Street, London WCIE 7HT, United Kingdom bRobens h~stitute of h~dustrial and Environmental Health and Sql'ety, UniversiO, of Surrey, GuiMford, Surrey GU2 5XH, United Kingdom (Received October 2nd, 1990; accepted November Ist, 1990)
ABSTRACT Blood lead levels were experimentally elevatea in two subjects by ingestion of single oral doses of lead as lead chloride. Serial samples of blood, urine and sweat were collected subsequently. Sweat samples were collected in polythene armbags while subjects cycled on a bicycle ergometer in a hot chamber. In spite of increases in blood and urinary lead levels, no increases in sweat lead levels were recorded. Possible reasons for this observation are discussed.
INTRODUCTION
Earlier studies have shown that lead is present in trace amounts in the sweat of non-occupationally exposed persons [1-3]. One of these studies showed a good relationship between blood lead and sweat lead levels [1]. It is possible that sweat losses of lead for occupationally exposed persons may help to reduce the body burden, particularly for workers in hot climates where daily sweat losses of up to 3 litres are possible. However, skin contamination of such workers makes the accurate determination of sweat lead levels difficult [4]. In an effort to overcome this problem, blood lead levels of two normal non-occupationally exposed persons were experimentally elevated to determine the pattern of sweat lead with rising blood lead levels. LEAD INGESTION STUDY
Lead as lead chloride was administered orally to two subjects, after ethical approval from the Committee for the Control of Clinical Investigation and * Present address: Department of Preventive and Socml Medicine, University College Hospital, Ibadan, Nigeria. 0048-9697/91/$03.50 ~ 1991 - - Elsevier Science Publishers B.V. All rights reserved
236
F.O. OMOKHODION AND G.W. CROCKFORD
Experiments on Humans. Physical examination, liver and kidney function tests were all normal. The target blood lead level was 40 pg/dl. The dose required to achieve this was estimated from published work on lead ingestion studies [5, 6]. METHOD
Sample collection Approximately 5 ml of blood was taken from the antecubital fossa using lithium heparin syringes. Urine samples were collected in polythene containers which had previously been soaked in 10% Jiitric acid. Sweat samples were collected in polythene armbags after careful scrubbing of the arms with lead-free soap (Phisohex). Arm rinses were collected prior to the collection of the first sweat sample. Arm bags were secured at the upper arm and at the wrists, thus excluding the hands. Sweat was collected while subjects cycled at intervals on a bicycle ergometer in a hot chamber. All samples were analysed by atomic absorption spectrophotometry. Details of method of sample collection and analysis have been published elsewhere [1]. Baseline estimations of blood, sweat and 24 h urinary lead levels were performed on both subjects. One of the aims of the first experiment on subject 1 was to determine the timing of the peak blood lead level after ingestion in order to identify the optimum time for sweat collection. On the day before the ingestion of lead, the subject fasted overnight from 8 p.m. that evening. On the morning of the experiment, a solution of 100 mg lead chloride in 100 ml deionised distilled water was prepared.
Su~iect 1 First ingestion Baseline samples of saliva and blood were collected at 10 a.m. Ten millilitres of the lead chloride solution (10 rag) was ingested at 12.00 |bllowed 0y 50 ml of water. Blood and saliva samples were collected 1, 2.5 and 4 h after ingestion. Sweat samples were collected for I h periods which ended 2.5 and 4.5 h after ingestion. A 24 h urine collection was started at 12.00. The peak blood level occurred 4 h after ingestion and was 23/~g/dl. On the basis of this, ingestion of 20 mg of lead was calculated.
Second ingestion The second ingestion experiment took place 4 days after the first. Again, baseline samples of blood, saliva and 24 h urine were taken. The subject drank 20ml of the lead solution (20mg lead chlo~ide) with about 50ml water at
237
SWEAT LEAD LEVELS IN PERSONS WITH HIGH BLOOD LEAD LEVELS
TABLE I Lead ingestion study. Lead concentrations in blood, sweat, and 24 h urine after oral administration of lead chloride. Subject i" 1st ingestion Date/time
Baseline, 30 Mar. 87 2 Apr. 87, 10rag ingested 12.00
Blood (/~g/dl) 9
13.00
12
14.25 15.55
17 23
Sweat (/tg/l)
Urine (/~g/I)
Left arm
Right arm
5.5
7.0
10
5.5 3.0
4.0 3.0
51
12.30 after fasting lbr 16 h. Blood samples were taken I, 2.5, 4, 5 and 6.5 h after the ingestion of lead. No saliva samples were taken on the day of the second ingestion experiment, as samples taken on the day of the first ingestion experiment were all contaminated by the ingested lead. Sweat samples were collected for I h periods which ended 1, 2.5, 4 and 6.5 h after the ingestion of lead. The first sweat sample was collected for 20 rnin only. Twenty-four-hour urine collection was started at 12.30. Blood samples were further collected on Days 1, 3, 7, 9 and 18. Sweat samples were collected on Days 1, 2 and 9. Twenty-four-hour urine collections were performed on Days 7 and 18.
Subject 2 At 14.45, this subject ingested a single 20mg dose of lead chloride in 20ml of water followed by about 100ml of water after fasting for 1511. Blood samples were taken 1, 2.5, 4 and 5 h after ingestion. Sweat was collected for I h periods which ended 1.5, 2.5 and 4 h after ingestion, and for a 0.5 h period which ended 4.5 h after the ingestion of iead. A 24h urine collection was star~ed at 14.30. Blood samples were further' coPected on Days 1, 3, 13 and 22, while sweat and urine samples were collected on Days 1 and 3. RESULTS
Blood lead levels were elevated to 23, 51 and 34/~g/dl in the three experiments. Peak blood lead levels were achieved in the fourth hour. Corresponding increases in urinary lead levels were recorded. However, no marked increases in sweat lead levels were observed in these experiments (Tables 1-3).
238
F.O. OMOKHODION AND G.W. CROCKFORD
TABLE 2 Lead ingestion study. Subject !: 2nd ingestion Date/time
Baseline, 6 Apr. 87 20mg ingested 12.30 13.30 15.00 16.30 17.30 19.00 7 Apr. 87 8 Apr. 87 9 Apr. 87 13 Apr. 87 15 Apr. 87 24 Apr. 87
Blood (jug/dl)
Sweat (#g/I)
Urine (l~g/i)
Left arm
Right arm
18
6.0
6.0
34 38 51 48 49 51
4.5 2.5 2.0
7.5 2.5 2.0
4.0 2.5 1.0
2.0 2.5 0.0
5.0
4.0
35 35 14 18
!7
97.4
27 35
DISCUSSION
The number of volunteers for these experiments was limited by ethical constraints. Howe-'er, following the ingestion of lead chloride by the two fasting subjects, their blood levels started rising within the first hour, but did not reach a peak until the fourth hour. Peak blood levels were maintained over TABLE 3 Lead ingestion study. Subject 2 Date/time
Blood (/~g/di)
Sweat (leg/I) Left arm
Baseline, 6 May 87 7 May 87, 20 mg ingested 14.45 i 5.45 17.15 18.45 19.20 8 May 87 10 May 87 20 May 87 29 May 87
Urine (/~g/I) Right arm
6.0
3.0
3.0
15
22.0 27.0 34.0 32.0 ~i 27 27 14
7.0 2.0 3.5 3.5 7.5 7.5
I i.0 2.0 1.0 5.0 3.5 3.5
67 57 31
SWEAT LEAD LEVELS IN PERSONS WITH HIGH BLOOD LEAD LEVELS
239
a 24 h period and fell progressively over the next few days. Despite marked increases in blood and urinary levels, no increase in sweat levels was recorded for subject 1. However, for subject 2, the sweat sample collected on the day of ingestion showed higher lead levels than the baseline level. The question arises as to whether or not this observation was due to a variation in the baseline sweat lead level or to a true rise in sweat lead level within the first hour after ingestion. The former is more probable because similar levels were repeated on Days 1 and 3. Furthermore, it is unlikely that plasma levels peaked within the first hour since this should correspond to a peak in whole blood lead levels, as demonstrated by DeSilva [6]. Chamberlain et al. [7] recorded a peak in blood lead level in the fourth hour, as in the present study, which corresponded to a peak in urinary excretion, an indication that plasma levels were at their peak during that period. These initial sweat levels for subject 2 can therelbre be regarded as a variation in baseline levels. The observation of a lack of res~,onse in sweat levels to sudden increases in blood levels is in line with that of other investigators who have studied the effect on sweat levels of a single dose of nickel [8] and iron [9]. Christensen et al. [8] gave a single dose of nickel to 16 healthy volunteers and observed no increase in sweat nickel in samples collected 3 h after ingestion, despite ,!emonstrable increases in blood and urinary levels. Johnston et al. [9] administered iron as ferric chloride to four subjects some hours prior to sweat collection and noted no increase in their sweat iron levels. Vellar administered an iron preparation orally to 19 subjects 2 h before sweat collection and observed no increase in their sweat iron levels [10]. There are two possible explanations for the lack of an increase in sweat levels in response to shard increases in blood levels. Firstly, there may be no direct movement of solutes from the plasma/blood pool to the sweat pool. if, on the other hand, direct movement does occur, it is extremely slow and would not take place in a matter of hours. Such sharp increases in blood lead levels may not be transferred to sweat over a few hours, during which time the lead will be rapidly distributed to soft tissue and bone, and urinary excretion, which involves a direct movement of plasma to the kidneys, will have eliminated excess lead [11]. A build-up of lead in the extra-cellular fluid may be required to induce an increase in sweat lead levels. However, experiments on human subjects using radio-isotopes of sodium and potassium indicate that these ions may be transported rapidly from plasma to the sweat pool. Gibinski [12], recorded sharp increases in sweat levels within 10min of intravenous and intracutaneous injections of42K and 24Na. It is possible that the skin absorption-extraction cycle [4] was responsible for the observation recorded after intracutaneous injections. On the other hand, isotope studies with lead show that the movement of lead from blood to the sweat pool is slow. Rabinowitz et al. [13] reported that 'other bodily output of lead such as
240
F.O. OMOKHODION AND G.W. CROCKFORD
sweat, hair, nails and digestive secretions do not appear to be isotopically equilibrated with whole blood'. The delay compared with the rapid labelling of blood and urinary lead, led him to conclude that sweat lead is derived from the second compartment of his three-compartment model, while urinary lead was excreted from the first, comprising of blood. If a delay in the movement of lead from the blood/plasma to the sweat compartment truly occurs, only long-term studies involving lead ingestion and sweat collection will simulate sweat losses in occupationally exposed persons. This has been demonstrated for nutrients such as zinc and iron, but such an experiment cannot be justified for a non-nutrient and a toxic material such as lead. Long-term supplementation of zinc and iron in previously deficient subjects has resulted in an increase in their sweat levels. Davies [14] administered zinc supplements to seven deficient subjects for a 3-5 month period and observed a rise in serum and sweat levels in all subjects. Earlier work by Howard (J.M. Howard, Biolab Medical Unit, London, unpublished data) in the same laboratory showed that serum zinc normalised earlier than sweat zinc levels in two deficient subjects receiving zinc supplementation. Hussain and Patwardhan [15] gave iron supplements to 17 anaemic women and observed that their cell-free sweat iron levels rose from 0 to 0.31 mg/l in 28 days and reached 0.41 mg/i in 42 days (mean level for normal subjects, 0.44 mg[l). It is not known exactly how long the transport of lead from the plasma/blood compartment to the sweat compartment takes, but indications from Howard's experiments with zinc supports the view that it is a matter of days or possibly weeks. In the present study, two s'ingle doses of lead for subject 1 and a single dose for subject 2 did not elicit an increase in sweat lead levels. Experiments carried out by Shells ie !o54 [16] suggested that sweat lead levels rose with dai!y oral intake of lead acetate given over a 5-day period. Sweat collected with cotton pads attached to the armpit during the last 3 days of lead ingestion contained twice as much lead as the sweat collected over the 3 days prior to lead ingestion. Surprisingly, urinary lead levels increased only marginally. No blood lead levels were recorded. Despite its limitations, Sheils" work indicates the possibility of increased sweat lead after multiple doses of oral lead, but the present study shows that this cannot be achieved by a single dose. It may be that recently absorbed lead in plasma is bound in some way that makes it unavailable to the sweat pool. On the other hand, a build-up of lead in blood as in long-term ingestion experiments or occupational exposure may be required to elicit an increase in sweat lead output. Analysis of lead in the sweat of five lead workers chronically exposed to lead, however, showed an increase over the levels recorded in non-exposed persons. A small group of lead workers with blood
SWEAT LI-AD LEVELS IN PERSONS WITH HIGH BLOOD LEAD LEVELS
241
lead levels of 42-62/tg/dl had sweat lead levels ranging from 20 to 75/ug/l, while non-exposed persons had levels of 6-13.6 ,ug/dl and 1.5-13.0/ug/l, respectively. Arm rinses collected before sweat collection contained < 2/ug/l lead. Another study of lead workers in the tropics showed much higher sweat lead values [4]. It appears, therefore, that the secretion of lead in sweat is increased in chronically exposed persons. However, the relationship between blood and sweat lead ,~,alues in this range of blood lead levels is not known. True sweat losses can be masked by external contamination of the skin. As this is difficult to eliminate, a degree of error is always present in sweat lead determinations in this group of persons. The demonstration of lead absorption by the skin by Florence et al. [17], and the possibility that lead thereby absorbed can be secreted back through the skin [4] further contributes to the masking of true sweat losses. it is possible that sweat lead values recorded for lead workers is a combination of lead excreted from body stores, external skin contamination and the secretion through the skin of lead previously absorbed via the same route. It can be concluded that losses of lead via sweat do not mirror rapid changes in blood lead levels. Long-term lead ingestion is not recommended as a method to elicit the pattern of lead loss in sweat. Isotope studies will be required to estimate 'true' sweat losses for lead workers and to elicit the time course of the movement of lead from the plasma to the sweat pool. REFERENCES I 2 3
4 5
6 7 8 9 10
F.O. Omokhodion and G.W. Crockford, Lead in sweat and its relationship to salivary and urinary levels in normal healthy subjects. Sci. Total Environ., 103 (I 99 I) I 13-122. J.L. Stauber and T.M. Florence, A comparative study of copper, lead, cadmium and zinc in hurnan sweat and blood. Sci. Total Environ., 74 (1988) 235-247. E.C.G. Grant, J.M. Howard, S. Davies, H. Chasly, B. Hornsby and J. Galbraith, Zinc deticiency in children with dyslexia: concentrations o1"zinc and other minerals in sweat and hair. Br. Med. J. (Clin. Res.), 296 (1988) 607-609. F.O. Ornokhodion and J.M. Howard, Sweat lead levels in persons with high blood lead levels: lead in sweat oflead workers in the tropics. Sci. Total Environ., 103 (1991) 123-128. A. Cools, H.J.A. Salle, M.M. Verberk and R.L. Zeilhuis, Biochemical response of male volunteers ingesting organic lead for 49 days. hat. Arch. Occup. Environ. Health, 38 (1976) 129-139. P.E. DeSilva, Determination of lead in plasma and studies on its relationship to lead in erythrocytes. Br. J. Ind. Med., 38 (1981) 2"9-217. A.C. Chamberlain, M.J. Heard, P. Little, D. Newton, A.C. Wells and R.D. Wiffen, Investigations into lead from motor vehicles. AERE R-9198, Harweil, 1978. O.B. Christensen, H. Moiler, L. Andrasko and V. Lagesson, Nickel concentration of blood, urine and sweat afier oral administration. CGntact Dermatitis, 5 (1979) 312-316. F.A. Johnston, T.J. McMillan and E.R. Evans, Perspiration as a factor influencing the requirement for calcium and iron. J. Nutr., 42 (1950) 485-496. O.D. Vellal, :Studies of sweat losses of nulrients. II. The influence of an oral iron load on
242
!I 12 13 14 15 16 17
F O. OMOKHODION AND G.W. {.'ROCKFORD
the iron content of whole body cell-free sweat. Scand. J. Clin. Lab. Invest., 21 (1968) 344-346. B.C. Campbell, P.A. Meredith, M.R. Moore and W.S. Watson, Kinetics of lead following intravenous administration in man. Toxicol. Lett., 21 (1984) 231-235. K. Gibinski, Some controversial problems in sweat gland function. Environ. Res., 4 (! 97 !) 265-389. M.B. Rabinowitz, G.W. Wetherill and J.D, Kopple, Kinetic analysis of lead metabolism iota healthy humans. J. Clin. Invest., 58 (1976) 260-270. S. Davies, Effects of oral zinc supplementation on serum, hair and sweat zinc levels in 7 subjects. Sci. Total En,~,~ron., 42 (1985) 45-48. R.L. Hussain and V.N. Patwardhan, Iron content of thermal sweat in iron deficiency anaemia. Lancet, I (1959) 1073. D.O. Sheils, The elimination of lead in sweat. Aust. Ann. Med,, 3 (1954) 225-229. T.M. Florence, S.G. Lilley and J.L. Stauber, Skin absorption of lead. Lancet, 2 (1988) 157.-158.
235
Sweat lead levels in persons with high blood lead levels: experimental elevation of blood lead by ingestion of lead chloride Folashade O. Omokhodion a'* and Goeffrey W. Crockford b Unit of Occupational Health, London School of Hygiene and Tropical Medicine, Keppei Street, London WCIE 7HT, United Kingdom bRobens h~stitute of h~dustrial and Environmental Health and Sql'ety, UniversiO, of Surrey, GuiMford, Surrey GU2 5XH, United Kingdom (Received October 2nd, 1990; accepted November Ist, 1990)
ABSTRACT Blood lead levels were experimentally elevatea in two subjects by ingestion of single oral doses of lead as lead chloride. Serial samples of blood, urine and sweat were collected subsequently. Sweat samples were collected in polythene armbags while subjects cycled on a bicycle ergometer in a hot chamber. In spite of increases in blood and urinary lead levels, no increases in sweat lead levels were recorded. Possible reasons for this observation are discussed.
INTRODUCTION
Earlier studies have shown that lead is present in trace amounts in the sweat of non-occupationally exposed persons [1-3]. One of these studies showed a good relationship between blood lead and sweat lead levels [1]. It is possible that sweat losses of lead for occupationally exposed persons may help to reduce the body burden, particularly for workers in hot climates where daily sweat losses of up to 3 litres are possible. However, skin contamination of such workers makes the accurate determination of sweat lead levels difficult [4]. In an effort to overcome this problem, blood lead levels of two normal non-occupationally exposed persons were experimentally elevated to determine the pattern of sweat lead with rising blood lead levels. LEAD INGESTION STUDY
Lead as lead chloride was administered orally to two subjects, after ethical approval from the Committee for the Control of Clinical Investigation and * Present address: Department of Preventive and Socml Medicine, University College Hospital, Ibadan, Nigeria. 0048-9697/91/$03.50 ~ 1991 - - Elsevier Science Publishers B.V. All rights reserved
236
F.O. OMOKHODION AND G.W. CROCKFORD
Experiments on Humans. Physical examination, liver and kidney function tests were all normal. The target blood lead level was 40 pg/dl. The dose required to achieve this was estimated from published work on lead ingestion studies [5, 6]. METHOD
Sample collection Approximately 5 ml of blood was taken from the antecubital fossa using lithium heparin syringes. Urine samples were collected in polythene containers which had previously been soaked in 10% Jiitric acid. Sweat samples were collected in polythene armbags after careful scrubbing of the arms with lead-free soap (Phisohex). Arm rinses were collected prior to the collection of the first sweat sample. Arm bags were secured at the upper arm and at the wrists, thus excluding the hands. Sweat was collected while subjects cycled at intervals on a bicycle ergometer in a hot chamber. All samples were analysed by atomic absorption spectrophotometry. Details of method of sample collection and analysis have been published elsewhere [1]. Baseline estimations of blood, sweat and 24 h urinary lead levels were performed on both subjects. One of the aims of the first experiment on subject 1 was to determine the timing of the peak blood lead level after ingestion in order to identify the optimum time for sweat collection. On the day before the ingestion of lead, the subject fasted overnight from 8 p.m. that evening. On the morning of the experiment, a solution of 100 mg lead chloride in 100 ml deionised distilled water was prepared.
Su~iect 1 First ingestion Baseline samples of saliva and blood were collected at 10 a.m. Ten millilitres of the lead chloride solution (10 rag) was ingested at 12.00 |bllowed 0y 50 ml of water. Blood and saliva samples were collected 1, 2.5 and 4 h after ingestion. Sweat samples were collected for I h periods which ended 2.5 and 4.5 h after ingestion. A 24 h urine collection was started at 12.00. The peak blood level occurred 4 h after ingestion and was 23/~g/dl. On the basis of this, ingestion of 20 mg of lead was calculated.
Second ingestion The second ingestion experiment took place 4 days after the first. Again, baseline samples of blood, saliva and 24 h urine were taken. The subject drank 20ml of the lead solution (20mg lead chlo~ide) with about 50ml water at
237
SWEAT LEAD LEVELS IN PERSONS WITH HIGH BLOOD LEAD LEVELS
TABLE I Lead ingestion study. Lead concentrations in blood, sweat, and 24 h urine after oral administration of lead chloride. Subject i" 1st ingestion Date/time
Baseline, 30 Mar. 87 2 Apr. 87, 10rag ingested 12.00
Blood (/~g/dl) 9
13.00
12
14.25 15.55
17 23
Sweat (/tg/l)
Urine (/~g/I)
Left arm
Right arm
5.5
7.0
10
5.5 3.0
4.0 3.0
51
12.30 after fasting lbr 16 h. Blood samples were taken I, 2.5, 4, 5 and 6.5 h after the ingestion of lead. No saliva samples were taken on the day of the second ingestion experiment, as samples taken on the day of the first ingestion experiment were all contaminated by the ingested lead. Sweat samples were collected for I h periods which ended 1, 2.5, 4 and 6.5 h after the ingestion of lead. The first sweat sample was collected for 20 rnin only. Twenty-four-hour urine collection was started at 12.30. Blood samples were further collected on Days 1, 3, 7, 9 and 18. Sweat samples were collected on Days 1, 2 and 9. Twenty-four-hour urine collections were performed on Days 7 and 18.
Subject 2 At 14.45, this subject ingested a single 20mg dose of lead chloride in 20ml of water followed by about 100ml of water after fasting for 1511. Blood samples were taken 1, 2.5, 4 and 5 h after ingestion. Sweat was collected for I h periods which ended 1.5, 2.5 and 4 h after ingestion, and for a 0.5 h period which ended 4.5 h after the ingestion of iead. A 24h urine collection was star~ed at 14.30. Blood samples were further' coPected on Days 1, 3, 13 and 22, while sweat and urine samples were collected on Days 1 and 3. RESULTS
Blood lead levels were elevated to 23, 51 and 34/~g/dl in the three experiments. Peak blood lead levels were achieved in the fourth hour. Corresponding increases in urinary lead levels were recorded. However, no marked increases in sweat lead levels were observed in these experiments (Tables 1-3).
238
F.O. OMOKHODION AND G.W. CROCKFORD
TABLE 2 Lead ingestion study. Subject !: 2nd ingestion Date/time
Baseline, 6 Apr. 87 20mg ingested 12.30 13.30 15.00 16.30 17.30 19.00 7 Apr. 87 8 Apr. 87 9 Apr. 87 13 Apr. 87 15 Apr. 87 24 Apr. 87
Blood (jug/dl)
Sweat (#g/I)
Urine (l~g/i)
Left arm
Right arm
18
6.0
6.0
34 38 51 48 49 51
4.5 2.5 2.0
7.5 2.5 2.0
4.0 2.5 1.0
2.0 2.5 0.0
5.0
4.0
35 35 14 18
!7
97.4
27 35
DISCUSSION
The number of volunteers for these experiments was limited by ethical constraints. Howe-'er, following the ingestion of lead chloride by the two fasting subjects, their blood levels started rising within the first hour, but did not reach a peak until the fourth hour. Peak blood levels were maintained over TABLE 3 Lead ingestion study. Subject 2 Date/time
Blood (/~g/di)
Sweat (leg/I) Left arm
Baseline, 6 May 87 7 May 87, 20 mg ingested 14.45 i 5.45 17.15 18.45 19.20 8 May 87 10 May 87 20 May 87 29 May 87
Urine (/~g/I) Right arm
6.0
3.0
3.0
15
22.0 27.0 34.0 32.0 ~i 27 27 14
7.0 2.0 3.5 3.5 7.5 7.5
I i.0 2.0 1.0 5.0 3.5 3.5
67 57 31
SWEAT LEAD LEVELS IN PERSONS WITH HIGH BLOOD LEAD LEVELS
239
a 24 h period and fell progressively over the next few days. Despite marked increases in blood and urinary levels, no increase in sweat levels was recorded for subject 1. However, for subject 2, the sweat sample collected on the day of ingestion showed higher lead levels than the baseline level. The question arises as to whether or not this observation was due to a variation in the baseline sweat lead level or to a true rise in sweat lead level within the first hour after ingestion. The former is more probable because similar levels were repeated on Days 1 and 3. Furthermore, it is unlikely that plasma levels peaked within the first hour since this should correspond to a peak in whole blood lead levels, as demonstrated by DeSilva [6]. Chamberlain et al. [7] recorded a peak in blood lead level in the fourth hour, as in the present study, which corresponded to a peak in urinary excretion, an indication that plasma levels were at their peak during that period. These initial sweat levels for subject 2 can therelbre be regarded as a variation in baseline levels. The observation of a lack of res~,onse in sweat levels to sudden increases in blood levels is in line with that of other investigators who have studied the effect on sweat levels of a single dose of nickel [8] and iron [9]. Christensen et al. [8] gave a single dose of nickel to 16 healthy volunteers and observed no increase in sweat nickel in samples collected 3 h after ingestion, despite ,!emonstrable increases in blood and urinary levels. Johnston et al. [9] administered iron as ferric chloride to four subjects some hours prior to sweat collection and noted no increase in their sweat iron levels. Vellar administered an iron preparation orally to 19 subjects 2 h before sweat collection and observed no increase in their sweat iron levels [10]. There are two possible explanations for the lack of an increase in sweat levels in response to shard increases in blood levels. Firstly, there may be no direct movement of solutes from the plasma/blood pool to the sweat pool. if, on the other hand, direct movement does occur, it is extremely slow and would not take place in a matter of hours. Such sharp increases in blood lead levels may not be transferred to sweat over a few hours, during which time the lead will be rapidly distributed to soft tissue and bone, and urinary excretion, which involves a direct movement of plasma to the kidneys, will have eliminated excess lead [11]. A build-up of lead in the extra-cellular fluid may be required to induce an increase in sweat lead levels. However, experiments on human subjects using radio-isotopes of sodium and potassium indicate that these ions may be transported rapidly from plasma to the sweat pool. Gibinski [12], recorded sharp increases in sweat levels within 10min of intravenous and intracutaneous injections of42K and 24Na. It is possible that the skin absorption-extraction cycle [4] was responsible for the observation recorded after intracutaneous injections. On the other hand, isotope studies with lead show that the movement of lead from blood to the sweat pool is slow. Rabinowitz et al. [13] reported that 'other bodily output of lead such as
240
F.O. OMOKHODION AND G.W. CROCKFORD
sweat, hair, nails and digestive secretions do not appear to be isotopically equilibrated with whole blood'. The delay compared with the rapid labelling of blood and urinary lead, led him to conclude that sweat lead is derived from the second compartment of his three-compartment model, while urinary lead was excreted from the first, comprising of blood. If a delay in the movement of lead from the blood/plasma to the sweat compartment truly occurs, only long-term studies involving lead ingestion and sweat collection will simulate sweat losses in occupationally exposed persons. This has been demonstrated for nutrients such as zinc and iron, but such an experiment cannot be justified for a non-nutrient and a toxic material such as lead. Long-term supplementation of zinc and iron in previously deficient subjects has resulted in an increase in their sweat levels. Davies [14] administered zinc supplements to seven deficient subjects for a 3-5 month period and observed a rise in serum and sweat levels in all subjects. Earlier work by Howard (J.M. Howard, Biolab Medical Unit, London, unpublished data) in the same laboratory showed that serum zinc normalised earlier than sweat zinc levels in two deficient subjects receiving zinc supplementation. Hussain and Patwardhan [15] gave iron supplements to 17 anaemic women and observed that their cell-free sweat iron levels rose from 0 to 0.31 mg/l in 28 days and reached 0.41 mg/i in 42 days (mean level for normal subjects, 0.44 mg[l). It is not known exactly how long the transport of lead from the plasma/blood compartment to the sweat compartment takes, but indications from Howard's experiments with zinc supports the view that it is a matter of days or possibly weeks. In the present study, two s'ingle doses of lead for subject 1 and a single dose for subject 2 did not elicit an increase in sweat lead levels. Experiments carried out by Shells ie !o54 [16] suggested that sweat lead levels rose with dai!y oral intake of lead acetate given over a 5-day period. Sweat collected with cotton pads attached to the armpit during the last 3 days of lead ingestion contained twice as much lead as the sweat collected over the 3 days prior to lead ingestion. Surprisingly, urinary lead levels increased only marginally. No blood lead levels were recorded. Despite its limitations, Sheils" work indicates the possibility of increased sweat lead after multiple doses of oral lead, but the present study shows that this cannot be achieved by a single dose. It may be that recently absorbed lead in plasma is bound in some way that makes it unavailable to the sweat pool. On the other hand, a build-up of lead in blood as in long-term ingestion experiments or occupational exposure may be required to elicit an increase in sweat lead output. Analysis of lead in the sweat of five lead workers chronically exposed to lead, however, showed an increase over the levels recorded in non-exposed persons. A small group of lead workers with blood
SWEAT LI-AD LEVELS IN PERSONS WITH HIGH BLOOD LEAD LEVELS
241
lead levels of 42-62/tg/dl had sweat lead levels ranging from 20 to 75/ug/l, while non-exposed persons had levels of 6-13.6 ,ug/dl and 1.5-13.0/ug/l, respectively. Arm rinses collected before sweat collection contained < 2/ug/l lead. Another study of lead workers in the tropics showed much higher sweat lead values [4]. It appears, therefore, that the secretion of lead in sweat is increased in chronically exposed persons. However, the relationship between blood and sweat lead ,~,alues in this range of blood lead levels is not known. True sweat losses can be masked by external contamination of the skin. As this is difficult to eliminate, a degree of error is always present in sweat lead determinations in this group of persons. The demonstration of lead absorption by the skin by Florence et al. [17], and the possibility that lead thereby absorbed can be secreted back through the skin [4] further contributes to the masking of true sweat losses. it is possible that sweat lead values recorded for lead workers is a combination of lead excreted from body stores, external skin contamination and the secretion through the skin of lead previously absorbed via the same route. It can be concluded that losses of lead via sweat do not mirror rapid changes in blood lead levels. Long-term lead ingestion is not recommended as a method to elicit the pattern of lead loss in sweat. Isotope studies will be required to estimate 'true' sweat losses for lead workers and to elicit the time course of the movement of lead from the plasma to the sweat pool. REFERENCES I 2 3
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