Skip to main content
PMC home page
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 2000 Jun;108(Suppl 3):483–490. doi: 10.1289/ehp.00108s3483

Workshop to identify critical windows of exposure for children's health: immune and respiratory systems work group summary.

R R Dietert 1, R A Etzel 1, D Chen 1, M Halonen 1, S D Holladay 1, A M Jarabek 1, K Landreth 1, D B Peden 1, K Pinkerton 1, R J Smialowicz 1, T Zoetis 1
PMCID: PMC1637823  PMID: 10852848

Abstract

Fetuses, infants, and juveniles (preadults) should not be considered simply "small adults" when it comes to toxicological risk. We present specific examples of developmental toxicants that are more toxic to children than to adults, focusing on effects on the immune and respiratory systems. We describe differences in both the pharmacokinetics of the developing immune and respiratory systems as well as changes in target organ sensitivities to toxicants. Differential windows of vulnerability during development are identified in the context of available animal models. We provide specific approaches to directly investigate differential windows of vulnerability. These approaches are based on fundamental developmental biology and the existence of discrete developmental processes within the immune and respiratory systems. The processes are likely to influence differential developmental susceptibility to toxicants, resulting in lifelong toxicological changes. We also provide a template for comparative research. Finally, we discuss the application of these data to risk assessment.

Full text

PDF
483

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barnett J. B., Blaylock B. L., Gandy J., Menna J. H., Denton R., Soderberg L. S. Long-term alteration of adult bone marrow colony formation by prenatal chlordane exposure. Fundam Appl Toxicol. 1990 May;14(4):688–695. doi: 10.1016/0272-0590(90)90294-t. [DOI] [PubMed] [Google Scholar]
  2. Barnett J. B., Soderberg L. S., Menna J. H. The effect of prenatal chlordane exposure on the delayed hypersensitivity response of BALB/c mice. Toxicol Lett. 1985 May;25(2):173–183. doi: 10.1016/0378-4274(85)90079-7. [DOI] [PubMed] [Google Scholar]
  3. Blaylock B. L., Holladay S. D., Comment C. E., Heindel J. J., Luster M. I. Exposure to tetrachlorodibenzo-p-dioxin (TCDD) alters fetal thymocyte maturation. Toxicol Appl Pharmacol. 1992 Feb;112(2):207–213. doi: 10.1016/0041-008x(92)90189-y. [DOI] [PubMed] [Google Scholar]
  4. Chen S., Golemboski K. A., Sanders F. S., Dietert R. R. Persistent effect of in utero meso-2,3-dimercaptosuccinic acid (DMSA) on immune function and lead-induced immunotoxicity. Toxicology. 1999 Jan 1;132(1):67–79. doi: 10.1016/s0300-483x(98)00139-5. [DOI] [PubMed] [Google Scholar]
  5. Colley J. R., Holland W. W., Corkhill R. T. Influence of passive smoking and parental phlegm on pneumonia and bronchitis in early childhood. Lancet. 1974 Nov 2;2(7888):1031–1034. doi: 10.1016/s0140-6736(74)92148-5. [DOI] [PubMed] [Google Scholar]
  6. Dearborn D. G., Yike I., Sorenson W. G., Miller M. J., Etzel R. A. Overview of investigations into pulmonary hemorrhage among infants in Cleveland, Ohio. Environ Health Perspect. 1999 Jun;107 (Suppl 3):495–499. doi: 10.1289/ehp.99107s3495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Etzel R. A., Montaña E., Sorenson W. G., Kullman G. J., Allan T. M., Dearborn D. G., Olson D. R., Jarvis B. B., Miller J. D. Acute pulmonary hemorrhage in infants associated with exposure to Stachybotrys atra and other fungi. Arch Pediatr Adolesc Med. 1998 Aug;152(8):757–762. doi: 10.1001/archpedi.152.8.757. [DOI] [PubMed] [Google Scholar]
  8. Faith R. E., Luster M. I., Kimmel C. A. Effect of chronic developmental lead exposure on cell-mediated immune functions. Clin Exp Immunol. 1979 Mar;35(3):413–420. [PMC free article] [PubMed] [Google Scholar]
  9. Fergusson D. M., Horwood L. J., Shannon F. T. Parental smoking and respiratory illness in infancy. Arch Dis Child. 1980 May;55(5):358–361. doi: 10.1136/adc.55.5.358. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fine J. S., Gasiewicz T. A., Silverstone A. E. Lymphocyte stem cell alterations following perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Mol Pharmacol. 1989 Jan;35(1):18–25. [PubMed] [Google Scholar]
  11. Gehrs B. C., Smialowicz R. J. Persistent suppression of delayed-type hypersensitivity in adult F344 rats after perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicology. 1999 May 3;134(1):79–88. doi: 10.1016/s0300-483x(99)00024-4. [DOI] [PubMed] [Google Scholar]
  12. Good R. A. Organization and development of the immune system. Relation to its reconstruction. Ann N Y Acad Sci. 1995 Dec 29;770:8–33. doi: 10.1111/j.1749-6632.1995.tb31040.x. [DOI] [PubMed] [Google Scholar]
  13. Harlap S., Davies A. M. Infant admissions to hospital and maternal smoking. Lancet. 1974 Mar 30;1(7857):529–532. doi: 10.1016/s0140-6736(74)92714-7. [DOI] [PubMed] [Google Scholar]
  14. Heo Y., Lee W. T., Lawrence D. A. In vivo the environmental pollutants lead and mercury induce oligoclonal T cell responses skewed toward type-2 reactivities. Cell Immunol. 1997 Aug 1;179(2):185–195. doi: 10.1006/cimm.1997.1160. [DOI] [PubMed] [Google Scholar]
  15. Holladay S. D., Smialowicz R. J. Development of the murine and human immune system: differential effects of immunotoxicants depend on time of exposure. Environ Health Perspect. 2000 Jun;108 (Suppl 3):463–473. doi: 10.1289/ehp.00108s3463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Jarabek A. M. The application of dosimetry models to identify key processes and parameters for default dose-response assessment approaches. Toxicol Lett. 1995 Sep;79(1-3):171–184. doi: 10.1016/0378-4274(95)03368-u. [DOI] [PubMed] [Google Scholar]
  17. Kerkvliet N. I., Baecher-Steppan L. Immunotoxicology studies on lead: effects of exposure on tumor growth and cell-mediated tumor immunity after syngeneic or allogeneic stimulation. Immunopharmacology. 1982 Jun;4(3):213–224. doi: 10.1016/0162-3109(82)90003-0. [DOI] [PubMed] [Google Scholar]
  18. Kimbell J. S., Gross E. A., Richardson R. B., Conolly R. B., Morgan K. T. Correlation of regional formaldehyde flux predictions with the distribution of formaldehyde-induced squamous metaplasia in F344 rat nasal passages. Mutat Res. 1997 Oct 31;380(1-2):143–154. doi: 10.1016/s0027-5107(97)00132-2. [DOI] [PubMed] [Google Scholar]
  19. Kowolenko M., Tracy L., Mudzinski S., Lawrence D. A. Effect of lead on macrophage function. J Leukoc Biol. 1988 Apr;43(4):357–364. doi: 10.1002/jlb.43.4.357. [DOI] [PubMed] [Google Scholar]
  20. Lai Z. W., Hundeiker C., Gleichmann E., Esser C. Cytokine gene expression during ontogeny in murine thymus on activation of the aryl hydrocarbon receptor by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Mol Pharmacol. 1997 Jul;52(1):30–37. doi: 10.1124/mol.52.1.30. [DOI] [PubMed] [Google Scholar]
  21. Levitzky M. G. Effects of aging on the respiratory system. Physiologist. 1984 Apr;27(2):102–107. [PubMed] [Google Scholar]
  22. Luster M. I., Faith R. E., Kimmel C. A. Depression of humoral immunity in rats following chronic developmental lead exposure. J Environ Pathol Toxicol. 1978 Mar-Apr;1(4):397–402. [PubMed] [Google Scholar]
  23. McDonnell W. F., Muller K. E., Bromberg P. A., Shy C. M. Predictors of individual differences in acute response to ozone exposure. Am Rev Respir Dis. 1993 Apr;147(4):818–825. doi: 10.1164/ajrccm/147.4.818. [DOI] [PubMed] [Google Scholar]
  24. Miller T. E., Golemboski K. A., Ha R. S., Bunn T., Sanders F. S., Dietert R. R. Developmental exposure to lead causes persistent immunotoxicity in Fischer 344 rats. Toxicol Sci. 1998 Apr;42(2):129–135. doi: 10.1006/toxs.1998.2424. [DOI] [PubMed] [Google Scholar]
  25. Morgan K. T., Kimbell J. S., Monticello T. M., Patra A. L., Fleishman A. Studies of inspiratory airflow patterns in the nasal passages of the F344 rat and rhesus monkey using nasal molds: relevance to formaldehyde toxicity. Toxicol Appl Pharmacol. 1991 Sep 1;110(2):223–240. doi: 10.1016/s0041-008x(05)80005-5. [DOI] [PubMed] [Google Scholar]
  26. Morgan K. T., Monticello T. M. Airflow, gas deposition, and lesion distribution in the nasal passages. Environ Health Perspect. 1990 Apr;85:209–218. doi: 10.1289/ehp.85-1568327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Müller A. M., Medvinsky A., Strouboulis J., Grosveld F., Dzierzak E. Development of hematopoietic stem cell activity in the mouse embryo. Immunity. 1994 Jul;1(4):291–301. doi: 10.1016/1074-7613(94)90081-7. [DOI] [PubMed] [Google Scholar]
  28. Nikulin M., Reijula K., Jarvis B. B., Hintikka E. L. Experimental lung mycotoxicosis in mice induced by Stachybotrys atra. Int J Exp Pathol. 1996 Oct;77(5):213–218. doi: 10.1046/j.1365-2613.1996.9250323.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Nikulin M., Reijula K., Jarvis B. B., Veijalainen P., Hintikka E. L. Effects of intranasal exposure to spores of Stachybotrys atra in mice. Fundam Appl Toxicol. 1997 Feb;35(2):182–188. [PubMed] [Google Scholar]
  30. Peden D. B. Development of atopy and asthma: candidate environmental influences and important periods of exposure. Environ Health Perspect. 2000 Jun;108 (Suppl 3):475–482. doi: 10.1289/ehp.00108s3475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Pinkerton K. E., Joad J. P. The mammalian respiratory system and critical windows of exposure for children's health. Environ Health Perspect. 2000 Jun;108 (Suppl 3):457–462. doi: 10.1289/ehp.00108s3457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Rantakallio P. Relationship of maternal smoking to morbidity and mortality of the child up to the age of five. Acta Paediatr Scand. 1978 Sep;67(5):621–631. doi: 10.1111/j.1651-2227.1978.tb17813.x. [DOI] [PubMed] [Google Scholar]
  33. Schulte P. A. A conceptual framework for the validation and use of biologic markers. Environ Res. 1989 Apr;48(2):129–144. doi: 10.1016/s0013-9351(89)80029-5. [DOI] [PubMed] [Google Scholar]
  34. Shortman K., Vremec D., Corcoran L. M., Georgopoulos K., Lucas K., Wu L. The linkage between T-cell and dendritic cell development in the mouse thymus. Immunol Rev. 1998 Oct;165:39–46. doi: 10.1111/j.1600-065x.1998.tb01228.x. [DOI] [PubMed] [Google Scholar]
  35. Sorenson W. G., Frazer D. G., Jarvis B. B., Simpson J., Robinson V. A. Trichothecene mycotoxins in aerosolized conidia of Stachybotrys atra. Appl Environ Microbiol. 1987 Jun;53(6):1370–1375. doi: 10.1128/aem.53.6.1370-1375.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Spyker-Cranmer J. M., Barnett J. B., Avery D. L., Cranmer M. F. Immunoteratology of chlordane: cell-mediated and humoral immune responses in adult mice exposed in utero. Toxicol Appl Pharmacol. 1982 Mar 15;62(3):402–408. doi: 10.1016/0041-008x(82)90141-7. [DOI] [PubMed] [Google Scholar]
  37. Tager I. B., Weiss S. T., Muñoz A., Rosner B., Speizer F. E. Longitudinal study of the effects of maternal smoking on pulmonary function in children. N Engl J Med. 1983 Sep 22;309(12):699–703. doi: 10.1056/NEJM198309223091204. [DOI] [PubMed] [Google Scholar]
  38. Urso P., Gengozian N. Alterations in the humoral immune response and tumor frequencies in mice exposed to benzo[a]pyrene and X-rays before or after birth. J Toxicol Environ Health. 1982 Oct-Nov;10(4-5):817–835. doi: 10.1080/15287398209530297. [DOI] [PubMed] [Google Scholar]
  39. Urso P., Gengozian N. Subnormal expression of cell-mediated and humoral immune responses in progeny disposed toward a high incidence of tumors after in utero exposure to benzo[a]pyrene. J Toxicol Environ Health. 1984;14(4):569–584. doi: 10.1080/15287398409530606. [DOI] [PubMed] [Google Scholar]
  40. Urso P., Johnson R. A. Early changes in T lymphocytes and subsets of mouse progeny defective as adults in controlling growth of a syngeneic tumor after in utero insult with benzo(a)pyrene. Immunopharmacology. 1987 Sep;14(1):1–10. doi: 10.1016/0162-3109(87)90003-8. [DOI] [PubMed] [Google Scholar]
  41. Ware J. H., Dockery D. W., Spiro A., 3rd, Speizer F. E., Ferris B. G., Jr Passive smoking, gas cooking, and respiratory health of children living in six cities. Am Rev Respir Dis. 1984 Mar;129(3):366–374. doi: 10.1164/arrd.1984.129.3.366. [DOI] [PubMed] [Google Scholar]
  42. Zelikoff J. T., Smialowicz R., Bigazzi P. E., Goyer R. A., Lawrence D. A., Maibach H. I., Gardner D. Immunomodulation by metals. Fundam Appl Toxicol. 1994 Jan;22(1):1–7. doi: 10.1006/faat.1994.1001. [DOI] [PubMed] [Google Scholar]
  43. Zon L. I. Developmental biology of hematopoiesis. Blood. 1995 Oct 15;86(8):2876–2891. [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES