Skip to main content
PMC home page
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 2001 Feb;109(2):187–192. doi: 10.1289/ehp.01109187

Children's health, susceptibility, and regulatory approaches to reducing risks from chemical carcinogens.

G Charnley 1, R M Putzrath 1
PMCID: PMC1240641  PMID: 11266331

Abstract

Risk-based regulation of chemical exposures from the environment generally relies on assumptions about the extent of people's susceptibility to chemically induced diseases. Those assumptions are intended to be health-protective; that is, they err on the side of overstating susceptibility. Recent concern about children's special susceptibilities has led to proposals that would make risk-based regulations one-tenth more stringent, unless data are available to refute the assumption that children are more susceptible than adults. In this paper we highlight some of the questions that should be addressed in the context of risk assessment to determine whether such increased stringency would accomplish the desired result of improving children's health. In particular, characterizing benefits of greater stringency requires more information about dose-response relationships than is currently available. Lowering regulatory levels has attendant costs but may not achieve benefits, for example, if the previous level were already below an actual or practical threshold. Without an ability to understand the potential benefit (or lack thereof) of the additional stringency, an appropriate consideration of benefits and costs is not possible.

Full Text

The Full Text of this article is available as a PDF (80.5 KB).

Selected References

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

  1. Anisimov V. N. Carcinogenesis and aging. I. Modifying effects of aging on N-methyl-N-nitrosourea-induced carcinogenesis in female rats. Exp Pathol. 1981;19(2):81–90. [PubMed] [Google Scholar]
  2. Anisimov V. N. Carcinogenesis and aging. III. The role of age in initiation and promotion of carcinogenesis. Exp Pathol. 1982;22(3):131–147. [PubMed] [Google Scholar]
  3. Anisimov V. N. Carcinogenesis and aging. Adv Cancer Res. 1983;40:365–424. doi: 10.1016/s0065-230x(08)60684-3. [DOI] [PubMed] [Google Scholar]
  4. Berry G., Wagner J. C. Effect of age at inoculation of asbestos on occurrence of mesotheliomas in rats. Int J Cancer. 1976 Apr 15;17(4):477–483. doi: 10.1002/ijc.2910170410. [DOI] [PubMed] [Google Scholar]
  5. Birnbaum L. S. Pharmacokinetic basis of age-related changes in sensitivity to toxicants. Annu Rev Pharmacol Toxicol. 1991;31:101–128. doi: 10.1146/annurev.pa.31.040191.000533. [DOI] [PubMed] [Google Scholar]
  6. COSGROVE G. E., UPTON A. C., SMITH L. H., DENT J. N. RADIATION GLOMERULOSCLEROSIS AND OTHER LATE EFFECTS: INFLUENCE OF RADIOLOGICAL FACTORS AND AET. Radiat Res. 1965 Aug;25:725–735. [PubMed] [Google Scholar]
  7. Castanera T. J., Jones D. C., Kimeldorf D. J., Rosen V. J. The effect of age at exposure to a sublethal dose of fast neutrons on tumorigenesis in the male rat. Cancer Res. 1971 Nov;31(11):1543–1549. [PubMed] [Google Scholar]
  8. Dedov V. I. Otdalennye posledstviia vnutrennego oblucheniia éndokrinnoi sistemy samok krys. Izv Akad Nauk SSSR Biol. 1982 May-Jun;(3):454–458. [PubMed] [Google Scholar]
  9. Dourson M. L., Baxter C. S. Reduced prevalence and growth rate of urethane-induced lung adenomas in ageing adult strain A mice. Toxicology. 1981;20(2-3):165–172. doi: 10.1016/0300-483x(81)90048-2. [DOI] [PubMed] [Google Scholar]
  10. Dourson M. L., Felter S. P., Robinson D. Evolution of science-based uncertainty factors in noncancer risk assessment. Regul Toxicol Pharmacol. 1996 Oct;24(2 Pt 1):108–120. doi: 10.1006/rtph.1996.0116. [DOI] [PubMed] [Google Scholar]
  11. Ebbesen P. Effect of age of non-skin tissues on susceptibility of skin grafts to 7,12-dimethylbenz[alpha]anthracene (DMBA) carcinogenesis in BALB/c mice, and effect of age of skin graft on susceptibility of surrounding recipient skin to DMBA. J Natl Cancer Inst. 1977 Apr;58(4):1057–1060. doi: 10.1093/jnci/58.4.1057. [DOI] [PubMed] [Google Scholar]
  12. Faustman E. M., Silbernagel S. M., Fenske R. A., Burbacher T. M., Ponce R. A. Mechanisms underlying Children's susceptibility to environmental toxicants. Environ Health Perspect. 2000 Mar;108 (Suppl 1):13–21. doi: 10.1289/ehp.00108s113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Franks L. M., Carbonell A. W. Effect of age on tumor induction in C57BL mice. J Natl Cancer Inst. 1974 Feb;52(2):565–564. doi: 10.1093/jnci/52.2.565. [DOI] [PubMed] [Google Scholar]
  14. Fukushima S., Shibata M., Tamano S., Ito N., Suzuki E., Okada M. Aging and urinary bladder carcinogenesis induced in rats by N-butyl-N-(4-hydroxybutyl)nitrosamine. J Natl Cancer Inst. 1987 Aug;79(2):263–267. [PubMed] [Google Scholar]
  15. Geschickter C. F. MAMMARY CARCINOMA IN THE RAT WITH METASTASIS INDUCED BY ESTROGEN. Science. 1939 Jan 13;89(2298):35–37. doi: 10.1126/science.89.2298.35-a. [DOI] [PubMed] [Google Scholar]
  16. Groth D. H., Coate W. B., Ulland B. M., Hornung R. W. Effects of aging on the induction of angiosarcoma. Environ Health Perspect. 1981 Oct;41:53–57. doi: 10.1289/ehp.814153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Grubbs C. J., Peckham J. C., Cato K. D. Mammary carcinogenesis in rats in relation to age at time of N-nitroso-N-methylurea administration. J Natl Cancer Inst. 1983 Jan;70(1):209–212. [PubMed] [Google Scholar]
  18. HUGGINS C., GRAND L. C., BRILLANTES F. P. Mammary cancer induced by a single feeding of polymucular hydrocarbons, and its suppression. Nature. 1961 Jan 21;189:204–207. doi: 10.1038/189204a0. [DOI] [PubMed] [Google Scholar]
  19. Hattis D., Banati P., Goble R. Distributions of individual susceptibility among humans for toxic effects. How much protection does the traditional tenfold factor provide for what fraction of which kinds of chemicals and effects? Ann N Y Acad Sci. 1999;895:286–316. doi: 10.1111/j.1749-6632.1999.tb08092.x. [DOI] [PubMed] [Google Scholar]
  20. Khudolei V. V. Rol' vozrasta v kantserogeneze, indutsirovannom N-nitrozodimetilaminom i N-dimetilnitraminom u amfibii Rana temporaria (L). Vopr Onkol. 1981;27(10):67–71. [PubMed] [Google Scholar]
  21. Kimura M., Fukuda T., Sato K. Effect of aging on the development of gastric cancer in rats induced by N-methyl-N'-nitro-N-nitrosoguanidine. Gan. 1979 Aug;70(4):521–525. [PubMed] [Google Scholar]
  22. Kroes R., Weiss J. W., Weisburger J. H. Immune suppression and chemical carcinogenesis. Recent Results Cancer Res. 1975;(52):65–75. doi: 10.1007/978-3-642-80940-8_9. [DOI] [PubMed] [Google Scholar]
  23. LINDOP P. J., ROTBLAT J. The age factor in the susceptibility of man and animals to radiation. I. The age factor in radiation sensitivity in mice. Br J Radiol. 1962 Jan;35:23–31. doi: 10.1259/0007-1285-35-409-23. [DOI] [PubMed] [Google Scholar]
  24. Lee P. N., Peto R. The effect of the age of mice on the incidence of skin cancer. Br J Cancer. 1970 Dec;24(4):849–852. doi: 10.1038/bjc.1970.100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. McGrath L. F., Cooper K. R., Georgopoulos P., Gallo M. A. Alternative models for low dose-response analysis of biochemical and immunological endpoints for tetrachlorodibenzo-p-dioxin. Regul Toxicol Pharmacol. 1995 Jun;21(3):382–396. doi: 10.1006/rtph.1995.1053. [DOI] [PubMed] [Google Scholar]
  26. Menczer J., Komarov H., Shenboum M., Insler V., Czernobilsky B. Attempted induction of granulosa cell tumor in Balb-C mice by gonadotropin administration. Gynecol Invest. 1977;8(5-6):314–322. doi: 10.1159/000301112. [DOI] [PubMed] [Google Scholar]
  27. Moon R. C., Fricks C. M. Influence of gonadal hormones and age on 1,2-dimethylhydrazine-induced colon carcinogenesis. Cancer. 1977 Nov;40(5 Suppl):2502–2508. doi: 10.1002/1097-0142(197711)40:5+<2502::aid-cncr2820400917>3.0.co;2-7. [DOI] [PubMed] [Google Scholar]
  28. Murai T., Mori S., Hosono M., Takeuchi Y., Ohhara T., Makino S., Hayashi Y., Takeda R., Fukushima S. Influences of aging and sex on renal pelvic carcinogenesis by N-butyl-N-(4-hydroxybutyl)nitrosamine in NON/Shi mice. Cancer Lett. 1994 Jan 30;76(2-3):147–153. doi: 10.1016/0304-3835(94)90391-3. [DOI] [PubMed] [Google Scholar]
  29. Ogiu T., Fukami H., Nishimura M., Shimada Y., Maekawa A. Age-dependent induction of thymic lymphomas by N-propyl-N-nitrosourea in the F344/DuCrj rat. Thymus. 1992 Dec;20(4):249–258. [PubMed] [Google Scholar]
  30. Paulini K., Beneke G., Körner B., Enders R. The relationship between the latent period and animal age in the development of foreign body sarcomas. Beitr Pathol. 1975;154(2):161–169. doi: 10.1016/s0005-8165(75)80209-5. [DOI] [PubMed] [Google Scholar]
  31. Pazmiño N. H., Yuhas J. M. Senescent loss of resistance to murine sarcoma virus (Moloney) in the mouse. Cancer Res. 1973 Nov;33(11):2668–2672. [PubMed] [Google Scholar]
  32. Peto R., Roe F. J., Lee P. N., Levy L., Clack J. Cancer and ageing in mice and men. Br J Cancer. 1975 Oct;32(4):411–426. doi: 10.1038/bjc.1975.242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Putzrath R. M. Reducing uncertainty of risk estimates for mixtures of chemicals within regulatory constraints. Regul Toxicol Pharmacol. 2000 Feb;31(1):44–52. doi: 10.1006/rtph.1999.1365. [DOI] [PubMed] [Google Scholar]
  34. Reuber M. D. Effect of age and sex on lesions of the esophagus in Buffalo strain rats ingesting diethylnitrosamine. Exp Cell Biol. 1976;44(2):65–72. doi: 10.1159/000163100. [DOI] [PubMed] [Google Scholar]
  35. Reuber M. D., Glover E. L. Hyperplastic and early neoplastic lesions of the liver in Buffalo strain rats of various ages given subcutaneous carbon tetrachloride. J Natl Cancer Inst. 1967 Jun;38(6):891–899. [PubMed] [Google Scholar]
  36. Reuber M. D. Hyperplastic and neoplastic lesions of the kidney in Buffalo rats of varying ages ingesting N-4-(4'-flurobiphenyl)acetamide. J Natl Cancer Inst. 1975 Feb;54(2):427–429. doi: 10.1093/jnci/54.2.427. [DOI] [PubMed] [Google Scholar]
  37. Reuber M. D., Lee C. W. Effect of age and sex on hepatic lesions in Buffalo strain rats ingesting diethylnitrosamine. J Natl Cancer Inst. 1968 Nov;41(5):1133–1140. [PubMed] [Google Scholar]
  38. Russo J., Russo I. H. DNA labeling index and structure of the rat mammary gland as determinants of its susceptibility to carcinogenesis. J Natl Cancer Inst. 1978 Dec;61(6):1451–1459. [PubMed] [Google Scholar]
  39. SAXEN E. A. On the factor of age in the production of subcutaneous sarcomas in mice by 20-methylcholanthrene. J Natl Cancer Inst. 1953 Dec;14(3):547–569. [PubMed] [Google Scholar]
  40. Savchenkov M. F., Benemanskii V. V., Levina V. Ia. Blastomogennaia aktivnost' dimetilnitrozoamina dlia zhivotnykh raznogo vozrasta. Gig Sanit. 1980 Apr;(4):17–20. [PubMed] [Google Scholar]
  41. Shirai T., Nakamura A., Fukushima S., Takahashi S., Ogawa K., Ito N. Effects of age on multiple organ carcinogenesis induced by 3,2'-dimethyl-4-aminobiphenyl in rats, with particular reference to the prostate. Jpn J Cancer Res. 1989 Apr;80(4):312–316. doi: 10.1111/j.1349-7006.1989.tb02312.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Sinha D. K., Pazik J. E., Dao T. L. Progression of rat mammary development with age and its relationship to carcinogenesis by a chemical carcinogen. Int J Cancer. 1983 Mar 15;31(3):321–327. doi: 10.1002/ijc.2910310312. [DOI] [PubMed] [Google Scholar]
  43. Stenbäck F., Peto R., Shubik P. Initiation and promotion at different ages and doses in 2200 mice. II. Decrease in promotion by TPA with ageing. Br J Cancer. 1981 Jul;44(1):15–23. doi: 10.1038/bjc.1981.142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Stromberg K., Reuber M. D. Histopathology of breast lesions induced in BUF rats of varying ages by ingestion of N-4-(4'-fluorobiphenyl) acetamide. J Natl Cancer Inst. 1975 May;54(5):1223–1230. doi: 10.1093/jnci/54.5.1223. [DOI] [PubMed] [Google Scholar]
  45. Stutman O. Chemical carcinogenesis in nude mice: comparison between nude mice from homozygous matings and heterozygous matings and effect of age and carcinogen dose. J Natl Cancer Inst. 1979 Feb;62(2):353–358. [PubMed] [Google Scholar]
  46. Summerhayes I. C., Franks L. M. Effects of donor age on neoplastic transformation of adult mouse bladder epithelium in vitro. J Natl Cancer Inst. 1979 Apr;62(4):1017–1023. [PubMed] [Google Scholar]
  47. Turusov V. S., Bazlova L. S., Krutovskikh V. A. Vliianie vozrasta, kastratsii i beremennosti na kantserogenez, indutsiruemyi 1,2-dimetilgidrazinom u myshei linii CBA. Biull Eksp Biol Med. 1979 May;87(5):458–460. [PubMed] [Google Scholar]
  48. Yoshida A., Harada T., Kitazawa T., Yoshida T., Kinoshita M., Maita K. Effects of age on endometrial carcinogenesis induced by concurrent oral administration of ethylenethiourea and sodium nitrite in mice. Exp Toxicol Pathol. 1996 Jun;48(4):289–298. doi: 10.1016/S0940-2993(96)80021-2. [DOI] [PubMed] [Google Scholar]
  49. Zimmerman J. A., Trombetta L. D., Carter T. H., Weisbroth S. H. Pancreatic carcinoma induced by N-methyl-N'-nitrosourea in aged mice. Gerontology. 1982;28(2):114–120. doi: 10.1159/000212520. [DOI] [PubMed] [Google Scholar]

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

RESOURCES