Tissue Mercury induced Levels Nephrotic in the Mercury- Syndrome R. D. BARR, M.R.C.P., H. SMITH, B . S C , P H . D . , AND H. M. CAMERON, M.D., F.R.C.PATH. Departments of Medicine and Pathology, University of Nairobi, Nairobi, Kenya, and Department of Forensic Medicine, University of Glasgow, Glasgow, Scotland ABSTRACT Barr, R. D., Smith, H., and Cameron, H. M.: Tissue mercury levels in the mercury-induced nephrotic syndrome. Am. J. Clin. Pathol. 59: 515-517, 1973. Levels of mercury in scalp hair, pubic hair, and fingernails were found to reflect the use of mercury-containing skin-lightening creams, the causal agents of many cases of the adult nephrotic syndrome seen in Africans in Kenya. STRONG EVIDENCE supporting an eiiologic relationship between the self-administration of skin-lightening creams containing ammoniated mercury and the development of a nephrotic syndrome has been presented by Barr and associates.1 Barr and colleagues 1 ' 2 have demonstrated good correlation between exposure to mercury in this form and levels of mercury in the urine of patients with nephrotic syndrome and normal individuals. However, since it has been shown that when the use of these preparations is discontinued, levels of mercury in urine fall to within normal limits in a period of a few weeks,2 it was decided to use a method of detecting previous exposure to mercury for a longer time interval following its use. Although the kidney retains more mercury than any other organ, 8 renal biopsy could not be justified simply to determine the presence or absence of mercury in the body. T h e metal is, however, readily detectable in other biologic materials; 10 therefore, hair and nails were chosen for analysis in the present study. Levels of mercury in hair and nails of subjects not known to have been exposed to the metal have been determined. 6 Patients and Methods Thirty-five patients, 27 women and 8 men, from the ages of 15 to 56 years, were included in the study. All were diagnosed as having nephrotic syndrome by standard criteria. Clippings of approximately the terminal half inch of scalp hair and pubic hair and clippings of fingernails were collected into plastic bags, and these specimens subsequently subjected to neutron activation analysis for the presence and quantity of mercury.10 There were fewer samples of pubic hair and nails than of scalp hair because of the common habits of shaving the pubic area and nail biting among the young women in this area. Analysis of the results was performed by the distribution free test of Kruskal and Wallis. 3 Results Received April 17, 1072; acceplcd for publication June IS, 11)72. Patients included in the study were sepaOr. Han's present address is: Department of rated into three groups based on their use Medicine, University of Aberdeen, Foresterhill, Abof skin-lightening creams containing mererdeen AB9 2ZD, Scotland, U.K. 515 516 A.J.C.P.—Vol. 59 BARR ET AL. Table 1. Analvsis of Results* Tissue Index Group A Group B 2341 12 28.4 189 13 14.5 Total of ranks Number of samples Mean rank Scalp hair Total of ranks Number of samples Mean 156 11 14.2 191 10 19.1 Total of ranks Number of samples Mean Chi-squared Chi-squared Chi-squared Chi-squared 59 7 8.4 6.95; p <0.05 4.86; p <0.05 2.09; 0.20 > p> 0.10 Chi-squared (A-B-C) Chi-squared (A—B+C) Chi-squared (B-C+A) Fingernails 100 10 10 19.98 p < 0.001 17.42 p < 0.001 2.56 p < 0.10 Chi-squared (A-B-C) Chi-squared (A-B+C) Chi-squared (B-C+A) Pubic hair Group C 140 9 15.6 207 11 18.8 88 9 9.8 5.63 0.10 > p> 0.05 3.56 0.10 > p> 0.05 2.07 0.20 > p> 0.10 4.90 p < 0.05 (A—B —C) (A-B+C) (C-B+A) (C—B+A) * Group A used skin-lightening creams containing mercury within 6 months of specimen sampling; group B discontinued use of skin-lightening creams more than 6 months before sampling; group C had not used skin-lightening creams at any time. Table 2. Tissue Mercury Levels (parts per million)* Tissue Scalp hair Group B Group A 20.5, 104, 898, 902, 2090, 3420, 252, 1280, 4800, Pubic hair 5.2, 31.9, 542, 22.7, 26, 50, 352, 824, 1470, Fingernails 5, 20.3, 156, 6.7, 78.8, 498, 9.4, 78.8, 840, 685, 1620, 9220 2.7, 11.2, 45.8, 768 27.3, 4.2, 11.4, 55.4, 17.7, 107, 1.1, 23.1, 274 Group C 5.4, 8.8, 10.5, 11.3, 11.3, 15, 57, 344, 490, 6.7, 8.5, 14.8, 27.1, 88.5, 1490 2.4, 40.5, 10.9, 29.1, 8.1, 10.9, 42, 152, 0.5, 0.6, 1.6, 10.8, 14.6, 14.9, 16.7, 20.1, 23.4 7.2, 1.8, 5.3, 0, 9.2, 19.7, 85 7.7, 0.4, 1.4, 2.6, 7.8, 8.9, 10, 13.2, 21.3, 22 * Group A used skin-lightening creams containing mercury within 6 months of specimen sampling; group B discontinued use of skin-lightening creams more than 6 months before sampling; group C had not used skin-lightening creams at any time. cury, as follows: group A had used these preparations within 6 months of specimen sampling; group B had discontinued the use of these creams more than 6 months before sampling; group C had not used skin-lightening creams containing mercury at any time. The numbers of samples from each group is noted in Table 1. Levels of mercury in hair and nails are expressed in Table 2. With regard to scalp and pubic hair, patients in group A had significantly higher mercury levels than did patients in the other two groups. There was no statistically significant difference among the levels of mercury in nails from patients in the three groups (Table 1). April 1973 MERCURY LEVELS AND NEPHROTIC SYNDROME Discussion The decision to separate patients in group A from those in group B on the basis of a time interval of 6 months prior to sampling was taken on the assumption that the mean hair length in our patients was approximately 3 in. and the average growth rate of hair was y2 in. per month. 5 Although levels of mercury in urine generally reflect current exposure to mercury, these levels may fluctuate widely in any individual. 2 ' 7 The usefulness of this estimation is restricted considerably when exposure to the metal has been discontinued. 2 Less direct evidence of exposure to mercury may be obtained from the demonstration of mercurialentis, 9 a fairly constant finding in situations of chronic exposure, often occurring in the absence of clinical evidence of systemic mercurialism.4 The results of the present study indicate that estimation of mercury in hair and nails, in addition to being reliable and completely safe, offers a useful direct means of detecting previous exposure to the metal. Scalp hair appears to be the most useful tissue in this respect. However, when the period between sampling and exposure to mercury is greater than 6 months, the mercury levels in scalp and pubic hair are not significantly different from those in individuals not exposed to mercury in the form of skin-lightening creams. This suggests that patients in group B have "excreted" their mercury load, probably in large part by cutting and washing the hair. Although no statistically significant difference among levels of mercury in nails in the three groups could be 517 demonstrated, inspection of the mean rank number for each group revealed the same trend as with scalp and pubic hair, i.e., A > B > C. Furthermore, statistical comparison of C to B + A gave a chi-square result suggesting a difference. These observations indicate that mercury may be excreted in nails at lower levels over longer periods of time. It is of considerable interest in this respect that the growth rate of nails is known to be much slower than that of hair. 5 The wide ranges of levels of mercury in groups A and B, for all three tissues, are believed to reflect great variability in rates of excretion of the metal. Acknowledgments. Mr. W. Gemert gave advice on the statistical analysis, Professor W. F. M. Fulton gave advice and encouragement, and Dr. P. J. Munano, Chief Administrator, Kenyatta National Hospital, Nairobi, gave permission to publish this report. References 1. Barr RD, Rees PH, Cordy PE, et al: The nephrotic syndrome in adult Africans in Nairobi. Br Med J 2:131-134, 1972 2. Barr RD, Woodger BA, Rees PH: Urine mercury levels and the use of skin-lightening creams. Am J Clin Pathol 59:35-40, 1973 3. Bradley JV: Distribution Free Statistical Tests. New York, Prentice-Hall, 1968, p 129 4. Burn RA: Mercurialentis. Proc Roy Soc Med 55:322-326, 1962 5. Glaister J: Medical Jurisprudence and Toxicology. Eleventh edition. Edinburgh, Livingstone, 1962, p 507 6. Howie RA, Smith H: Mercury in human tissue. J Forensic Sci Soc 7:90-96, 1967 7. Jacobs MB, Ladd AC, Goldwalter LJ: Absorption and excretion of mercury in man. Arch Environ Health 9:454-463, 1964 8. Kazantsis G: Mercury and the kidney. Trans Soc Occup Med 20:54-59, 1970 9. Locket S, Nazroo IA: Eye changes following exposure to metallic mercury. Lancet 1:528-530, 1952 10. Smith H: Estimation of mercury in biological material by neutron activation analysis. Anal Chem 35:635-636, 1963
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