Risk assessment in relation to neonatal metal exposure†

Abstract

Rapid changes in organ development and function occur during the neonatal period. During this period the central nervous system is in a rapid growth rate and highly vulnerable to toxic effects of, e.g., lead and methylmercury. Furthermore, the kinetics of many metals is age-specific, with a higher gastrointestinal absorption, less effective renal excretion as well as a less effective blood-brain barrier in newborns compared to adults. Due to their low body weight and high food consumption per kg of body weight, the tissue levels of contaminants can reach higher levels in newborns than in adults. Generally, there is a low transfer of toxic metals through milk when maternal exposure levels are low. However, knowledge is limited about the lactational transport of metals and the potential effects of metals in the mammary gland on milk secretion and composition. There are some data from rodents on the lactational transfer and the uptake in the neonate of inorganic mercury, methylmercury, lead and cadmium. Metal levels in human breast milk and blood samples from different exposure situations can give information on the correlation between blood and milk levels. If such a relationship exists, milk levels can be used as an indicator of both maternal and neonatal exposure. Better understanding of the neonatal exposure, including kinetics in the lactating mother and in the newborn, and effects of toxic metals in different age groups is needed for the risk assessment. Interactions with nutritional factors and the great beneficial value of breast-feeding should also be considered.

References

1. IPCS, Environmental Health Criteria 70, Principles for the Safety Assessment of Food Additives and Contaminants in Food, World Health Organization, Geneva, 1987.
2. IPCS, Environmental Health Criteria 59, Principles for Evaluating Health Risks From Chemicals During Infancy and Early Childhood: The Need for a Special Approach, World Health Organization, Geneva, 1986.
3. Similarities and Differences Between Children and Adults. Implications for Risk Assessment, ed. Guzelian, P. S., Henry, C. J., and Olin, S. S., ILSI Press, Washington, DC, 1992.
4. I. Palminger Hallén, S. Jönsson, M. O. Karlsson and A. Oskarsson, Toxicol. Appl. Pharmacol., 1996, 136, 342.
5. M. R. Greenwood, T. W. Clarkson, R. A. Doherty, A. H. Gates, L. Amin-Zaki, S. Elhassani and M. A. Majeed, Environ. Res., 1978, 16, 48.
6. J. Sundberg, S. Jönsson, M. O. Karlsson, I. Palminger Hallén and A. Oskarsson, unpublished work.
7. Lactation: Physiology, Nutrition and Breast-feeding, ed. Neville, M. C., and Neifert, M. R., Plenum Press, New York, 1983.
8. J. T. Wilson, Drug Metab. Rev., 1983, 14, 619.
9. WHO Working Group in Drugs and Human Lactation, ed. Bennett, P. N., Elsevier, Amsterdam, 1988, pp. 27–48.
10. I. Palminger Hallén and A. Oskarsson, Biometals, 1995, 8, 231.
11. K. Petersson and A. Oskarsson, unpublished work.
12. J. Sundberg, B. Ersson and A. Oskarsson, unpublished work.
13. C. E. Casey, A. Smith and P. Zhang, in Handbook of Milk Composition, ed. Jensen, R. G., Academic Press, San Diego, California, 1995, pp. 622–674.
14. G.-B. Fransson and B. Lönnerdal, Ped. Res., 1983, 17, 912.
15. I. Palminger Hallén, L. Norrgren and A. Oskarsson, Arch. Toxicol., 1996, 70, 237.
16. A. Oskarsson, I. Palminger Hallén and J. Sundberg, Analyst, 1995, 120, 765.
17. I. Palminger Hallén, L. Jorhem, B. Json Lagerkvist and A. Oskarsson, Sci. Total Environ., 1995, 166, 149.
18. A. Oskarsson, A. Schütz, S. Skerfving, I. Palminger Hallén, B. Ohlin and B. Json Lagerkvist, Arch. Environ. Health, 1996, 51, 234.
19. WHO/FAO, Toxicological Evaluation of Certain Food Additives and Contaminants, World Health Organization Food Additives Series: 24, Cambridge University Press, 1989.
20. P. Grandjean, P. J. Jørgensen and P. Weihe, Environ. Health Perspect., 1994, 102, 74.
21. IPCS, Environmental Health Criteria, Copper, World Health Organization, Geneva, in the press.
22. G. Eklund, S. Helmersson and A. Oskarsson, unpublished results.
23. R. L. Milsap, M. R. Hill and S. J. Szefler, in Applied Pharmacokinetics: Principles of Therapeutic Drug Monitoring, ed. Evans, W. E., Scentag, J. J., and Jusko, W. J., Applied Therapeutics, Vancouver, Washington, 3rd edn., 1992, pp. 10-1-32.
24. J. M. Davis and L. D. Grant, in Similarities and Differences Between Children and Adults. Implications for Risk Assessment, ed. Guzelian, P. S., Henry, C. J., and Olin, S. S., ILSI Press, Washington, DC, 1992, pp. 150–162.
25. S. J. Henning and L. C. Cooper, Proc. Soc. Exp. Biol. Med., 1988, 187, 110.
26. D. Kello and K. Kostial, Environ. Res., 1973, 6, 355.
27. I. Palminger Hallén, S. Jönsson, M. O. Karlsson and A. Oskarsson, Toxicol. Appl. Pharmacol., 1996, 140, 13.
28. Department of the Environment Central Directorate on Environmental Pollution, The Glasgow Duplicate Diet Study (1979/80), Pollution Report No. 11, 1982.
29. I. R. Rowland, R. D. Robinson, R. A. Doherty and T. D. Landry, in Reproductive and Developmental Toxicity of Metals, ed. Clarkson, T. W., Nordberg, G. F., and Sager, P. R., Plenum Press, New York, 1983, p. 745.
30. B. Momcilovic and K. Kostial, Environ. Res., 1974, 8, 214.
31. K. Kostial, D. Kello, S. Jugo, I. Rabar and T. Maljkovic, Environ. Health Perspect., 1978, 25, 81.
32. K. L. Wong and C. Klaassen, Toxicol. Appl. Pharmacol., 1980, 53, 343.
33. S. Jugo, Environ. Res., 1980, 21, 336.
34. A. N. Davison and J. Dobbing, in Applied Neurochemistry, ed. Davison, A. N., and Dobbing, J., Blackwell Scientific Publications, Oxford, 1968, pp. 253–282.
35. IPCS, Environmental Health Criteria 165, Lead, World Health Organization, Geneva, 1995.
36. G. J. Myers, P. W. Davidson, C. Cox, C. F. Shamlaye, M. A. Tanner, D. O. Marsh, E. Cernichiari, L. W. Lapham, M. Berlin and T. W. Clarkson, Neurotoxicol., 1995, 16, 711.
37. D. O. Marsh, M. D. Turner, J. Crispin Smith, P. Allen and N. Richdale, Neurotoxicol., 1995, 16, 717.
38. P. Grandjean, P. Weihe, R. F. White, F. Debes, S. Araki, K. Yokoyama, K. Murata, N. Sørensen, R. Dahl, E. Budtz- Jørgensen and P. J. Jørgensen, Abstract presented at the International Conference on Human Health Effects of Mercury Exposure, Tórshavn, Faroe Islands, June 22–26, 1997.
39. K. L. Wong and C. D. Klaassen, Toxicol. Appl. Pharmacol., 1982, 63, 330.
40. M. J. Smith, R. O. Pihl and B. Farrell, Neurobehav. Toxicol. Teratol., 1985, 7, 19.
41. H. Andersson, K. Petersson-Grawé, E. Lindqvist, J. Luthman, A. Oskarsson and L. Olson, Neurotoxicol. Teratol., 1997, 19, 105.
42. A. Thuvander, J. Sundberg and A. Oskarsson, Toxicology, 1997, 114, 163.
43. J. S. Forsyth, Proc. Nutr. Soc., 1995, 54, 407.
44. A. Håkansson, B. Zhivotovsky, S. Orrenius, H. Sabharwal and C. Svanborg, Proc. Natl. Acad., Sci., 1995, 92, 8064.
45. R. Uauy and I. Andraca, J. Nutr., 1995, 125, 2278S.
46. C. R. Gale and C. N. Martyn, Lancet, 1996, 347, 1072.
47. K. F. Michaelsen, P. S. Larsen, B. L. Thomsen and G. Samuelson, Acta Paed., 1994, 83, 565.