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Mercury in hair—but from where?
CORRESPONDENCE
The most appropriate drug-exposure model can usually be determined objectively by the data, without recourse to a subjective value judgment of appropriateness.2,3 Such objective methods are important because the exposure measure that they give might not be similar to that chosen intuitively. The validation of cases should be carried out with caution, and preferably only when it is possible to validate each case. We have found that the existence or availability of case records varies between patients, which could theoretically be associated with exposure status.4 If cases are excluded from a study because it is not possible to validate them, there is the potential for selection bias with unpredictable results. Without case validation, there is potential for misclassification, but if this is non-differential it will tend to bias a result towards the null hypothesis, and is therefore predictable. We would also like to recommend the use of the case-crossover design in drug epidemiology. This design is suitable for transient risks, and the main advantage is the way in which confounding is neatly dealt with.4 With respect to the accurate definition of exposure measures by computerised medical information, we believe the ability to identify prescriptions that have actually been dispensed to patients in the pharmacy (rather than prescribed by the doctor) is an advantage since many prescriptions are never redeemed by patients. Otherwise, exposure misclassification due to primary non-compliance can be introduced, in that patients who do not redeem their prescriptions are erroneously classified as exposed. *T M MacDonald, J M M Evans, F Sullivan, A D McMahon *Medicines Monitoring Unit and Department of General Practice, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK 1
2
3
4
MacDonald TM, McDevitt DG. The Tayside Medicines Monitoring Unit (MEMO). In: Strom BL, ed. Pharmacoepidemiology, second edition. Chichester: John Wiley & Sons Ltd, 1994; 245–55. McMahon AD, Evans JMM, McGilchrist MM, McDevitt DG, MacDonald TM. Drug exposure risk windows and unexposed comparator groups for cohort studies in pharmacoepidemiology. Pharmacoepidemiol Drug Safety 1988; 7: 275–80. Evans JMM, MacDonald TM. Misclassification and selection bias in casecontrol studies using an automated database. Pharmacoepidemiol Drug Safety 1997; 6: 313–18. Barbone F, McMahon AD, Davey PG, et al. Association of road-traffic accidents with benzodiazepine use. Lancet 1998; 352: 1331–36.
502
Mercury in hair—but from where? Sir—Susan Maloney and colleagues (Nov 14, p 1602)1 ascribe increased concentrations of mercury in hair to occupational exposure from working in crematoria. Care must be taken when hair samples are used to monitor exposure to differentiate between external contamination and true deposition of absorbed and retained mercury. Further, the analytical method used by Maloney and co-workers will show the total amount of mercury, but not the species. Thus, mercury from dental amalgam and from exposure to methylmercury will eventually end up as mercury in hair. In the study by Maloney and colleagues, the ratio between mean concentration of mercury in hair and the number of fillings was identical in all three occupational groups, indicating that the exposure of the three groups was not, as described by the investigators, different but simply that more fillings caused higher mercury in hair. The concentration of mercury in the occupational group was nevertheless higher than in age-matched controls, thus indicating additional mercury exposure. However, as methylmercury exposure from fish is usually the main cause of mercury deposited in hair, variations in dietary habits may well hide small differences related to occupational mercury vapour exposure.2 *Jesper B Nielsen, Philippe Grandjean Department of Environmental Medicine, Odense University, DK-5000 Odense C, Denmark 1
2
Maloney SR, Phillips CA, Mills A. Mercury in the hair of crematoria workers. Lancet 1998; 352: 1602. Grandjean P, Weihe P, Nielsen JB. Methylmercury: significance of intrauterine and postnatal exposures. Clin Chem 1994; 40: 1395–400.
Authors’ reply Sir—Jesper Nielsen and Philippe Grandjean’s suggestion of external contamination is accepted by most workers in the field. However, there are also drawbacks associated with blood and urine measurements, the former being more appropriate for monitoring of methylmercury, while urine reflects recent exposure and subsequent elimination of mercury from the body. In our study, hair was chosen since it represents a long time scale without the need to take other variables on exposure times into account, although we deemed a standard week of 35 h or longer acceptable for inclusion in the trial group.1 External contamination of the
hair was controlled as far as possible by careful washing. Hair has been used in many population studies.2 Any methylmercury present in the hair could arise from consumption of contaminated fish. However, unlike the Scandinavian countries, fish is not a major part of the diet in the UK, and 50–60% of people do not include fish as a regular part of their diet. We believe that the methylmercury intake from this amount of fish would be unlikely to be high enough to cause sufficient variation to confound the results. This assertion is supported by our preliminary experiments on some hair samples, to identify the mercury species, which showed that methylmercury was present in amounts lower than the limits of our detection system. Nielson and Grandjean correctly state that there seems to be a correlation between the number of fillings and the mean mercury concentrations for each occupational group. However, further analysis showed this explanation to be purely superficial. Exposure to mercury does seem to arise from dental amalgam restorations and an average of 2–20 mg per day has been estimated.3 It is difficult, however, to satisfactorily correlate the number of fillings with measurements of mercury because of confounding factors such as the size of the filling, the time of placement, chewing activity, and recent dental work. We found no correlation between the number of fillings and the mercury concentrations in the control group. The trial group and individual occupational groups gave similar or worse results. Although there was a significant difference in mercury concentrations between occupational groups, the differences in the number of fillings between the groups was not significant (p=0·3). The differences in mercury concentrations between the groups was small, however, and further investigation may be indicated. Susan R Maloney, Carol A Phillips, Simon Langley-Evans, *Allan Mills Centre for Healthcare Education, Faculty of Applied Sciences, University College Northampton, Northampton NN2 7AL, UK; and *Department of Geology, University of Leicester, Leicester 1
2
3
Maloney SR, Phillips CA, Mills A. Mercury in the hair of crematoria workers. Lancet 1998; 352: 1602. Gerstenberger SL, Tarvis DR, Hansen LK, Pratt-Shelley J, Dellinger JA. Concentrations of blood and hair mercury and serum PCBs in an Ojibwa population that consumes Great Lakes region fish. Clinical Toxicol 1997; 35: 377–86. Begerow J, Zander D, Freier I, Dunemann L. Long-term mercury excretion in urine after removal of amalgam fillings. Arch Occup Environ Health 1994; 17: 263–68.
THE LANCET • Vol 353 • February 6, 1999
The most appropriate drug-exposure model can usually be determined objectively by the data, without recourse to a subjective value judgment of appropriateness.2,3 Such objective methods are important because the exposure measure that they give might not be similar to that chosen intuitively. The validation of cases should be carried out with caution, and preferably only when it is possible to validate each case. We have found that the existence or availability of case records varies between patients, which could theoretically be associated with exposure status.4 If cases are excluded from a study because it is not possible to validate them, there is the potential for selection bias with unpredictable results. Without case validation, there is potential for misclassification, but if this is non-differential it will tend to bias a result towards the null hypothesis, and is therefore predictable. We would also like to recommend the use of the case-crossover design in drug epidemiology. This design is suitable for transient risks, and the main advantage is the way in which confounding is neatly dealt with.4 With respect to the accurate definition of exposure measures by computerised medical information, we believe the ability to identify prescriptions that have actually been dispensed to patients in the pharmacy (rather than prescribed by the doctor) is an advantage since many prescriptions are never redeemed by patients. Otherwise, exposure misclassification due to primary non-compliance can be introduced, in that patients who do not redeem their prescriptions are erroneously classified as exposed. *T M MacDonald, J M M Evans, F Sullivan, A D McMahon *Medicines Monitoring Unit and Department of General Practice, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK 1
2
3
4
MacDonald TM, McDevitt DG. The Tayside Medicines Monitoring Unit (MEMO). In: Strom BL, ed. Pharmacoepidemiology, second edition. Chichester: John Wiley & Sons Ltd, 1994; 245–55. McMahon AD, Evans JMM, McGilchrist MM, McDevitt DG, MacDonald TM. Drug exposure risk windows and unexposed comparator groups for cohort studies in pharmacoepidemiology. Pharmacoepidemiol Drug Safety 1988; 7: 275–80. Evans JMM, MacDonald TM. Misclassification and selection bias in casecontrol studies using an automated database. Pharmacoepidemiol Drug Safety 1997; 6: 313–18. Barbone F, McMahon AD, Davey PG, et al. Association of road-traffic accidents with benzodiazepine use. Lancet 1998; 352: 1331–36.
502
Mercury in hair—but from where? Sir—Susan Maloney and colleagues (Nov 14, p 1602)1 ascribe increased concentrations of mercury in hair to occupational exposure from working in crematoria. Care must be taken when hair samples are used to monitor exposure to differentiate between external contamination and true deposition of absorbed and retained mercury. Further, the analytical method used by Maloney and co-workers will show the total amount of mercury, but not the species. Thus, mercury from dental amalgam and from exposure to methylmercury will eventually end up as mercury in hair. In the study by Maloney and colleagues, the ratio between mean concentration of mercury in hair and the number of fillings was identical in all three occupational groups, indicating that the exposure of the three groups was not, as described by the investigators, different but simply that more fillings caused higher mercury in hair. The concentration of mercury in the occupational group was nevertheless higher than in age-matched controls, thus indicating additional mercury exposure. However, as methylmercury exposure from fish is usually the main cause of mercury deposited in hair, variations in dietary habits may well hide small differences related to occupational mercury vapour exposure.2 *Jesper B Nielsen, Philippe Grandjean Department of Environmental Medicine, Odense University, DK-5000 Odense C, Denmark 1
2
Maloney SR, Phillips CA, Mills A. Mercury in the hair of crematoria workers. Lancet 1998; 352: 1602. Grandjean P, Weihe P, Nielsen JB. Methylmercury: significance of intrauterine and postnatal exposures. Clin Chem 1994; 40: 1395–400.
Authors’ reply Sir—Jesper Nielsen and Philippe Grandjean’s suggestion of external contamination is accepted by most workers in the field. However, there are also drawbacks associated with blood and urine measurements, the former being more appropriate for monitoring of methylmercury, while urine reflects recent exposure and subsequent elimination of mercury from the body. In our study, hair was chosen since it represents a long time scale without the need to take other variables on exposure times into account, although we deemed a standard week of 35 h or longer acceptable for inclusion in the trial group.1 External contamination of the
hair was controlled as far as possible by careful washing. Hair has been used in many population studies.2 Any methylmercury present in the hair could arise from consumption of contaminated fish. However, unlike the Scandinavian countries, fish is not a major part of the diet in the UK, and 50–60% of people do not include fish as a regular part of their diet. We believe that the methylmercury intake from this amount of fish would be unlikely to be high enough to cause sufficient variation to confound the results. This assertion is supported by our preliminary experiments on some hair samples, to identify the mercury species, which showed that methylmercury was present in amounts lower than the limits of our detection system. Nielson and Grandjean correctly state that there seems to be a correlation between the number of fillings and the mean mercury concentrations for each occupational group. However, further analysis showed this explanation to be purely superficial. Exposure to mercury does seem to arise from dental amalgam restorations and an average of 2–20 mg per day has been estimated.3 It is difficult, however, to satisfactorily correlate the number of fillings with measurements of mercury because of confounding factors such as the size of the filling, the time of placement, chewing activity, and recent dental work. We found no correlation between the number of fillings and the mercury concentrations in the control group. The trial group and individual occupational groups gave similar or worse results. Although there was a significant difference in mercury concentrations between occupational groups, the differences in the number of fillings between the groups was not significant (p=0·3). The differences in mercury concentrations between the groups was small, however, and further investigation may be indicated. Susan R Maloney, Carol A Phillips, Simon Langley-Evans, *Allan Mills Centre for Healthcare Education, Faculty of Applied Sciences, University College Northampton, Northampton NN2 7AL, UK; and *Department of Geology, University of Leicester, Leicester 1
2
3
Maloney SR, Phillips CA, Mills A. Mercury in the hair of crematoria workers. Lancet 1998; 352: 1602. Gerstenberger SL, Tarvis DR, Hansen LK, Pratt-Shelley J, Dellinger JA. Concentrations of blood and hair mercury and serum PCBs in an Ojibwa population that consumes Great Lakes region fish. Clinical Toxicol 1997; 35: 377–86. Begerow J, Zander D, Freier I, Dunemann L. Long-term mercury excretion in urine after removal of amalgam fillings. Arch Occup Environ Health 1994; 17: 263–68.
THE LANCET • Vol 353 • February 6, 1999