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Science Feature

Dioxin Update: Children are the Most Vulnerable

Perhaps the most important, and most disturbing, new evidence about dioxin's toxicity is the neurodevelopmental and reproductive effects observed in children.  Much of this evidence comes from a large multi-study evaluation of children from the general population of the Netherlands (1,2).  In these studies, children exposed to higher levels of dioxins and PCBs suffered more neurological, developmental, reproductive, and immune effects than children exposed to lower levels.  Some of the effects include a four point IQ deficit (3), an increased prevalence of hyperactive behavior (4), and an increased prevalence of withdrawn and depressed behavior (5).

This study, called the"Dutch PCB/Dioxin Study," began in 1989 in response to the discovery of very high levels of dioxins and PCBs in Dutch breast milk (1). The aim of the study was to evaluate adverse effects of exposure to PCBs and dioxins on the growth and development of children (1). Mothers and their infants from two cities (Rotterdam and Groningen) were included in the study.  Several studies included children from both cities, others just from one.  Participating mothers had only been exposed to "background" levels of dioxins and PCBs.  These background levels resulted from the mother's daily intake of dioxin in food.  The study group consisted of 418 healthy mother-infant pairs, split  equally between the two communities.  Half the children were breast-fed and half were formula fed.  The children were examined just after birth and at different intervals, most recently at 42 months of age.  The health of these children continues to be followed today.

Dioxin and PCB exposure was measured in three ways: prenatal, postnatal, and current exposures.  Prenatal exposure is a measure of what a child is exposed to before birth, while in the mother's womb.  Effects associated with prenatal exposure occurred in the children who were formula-fed.  Prenatal exposure to PCBs was measured in maternal blood collected during the last month of pregnancy and in umbilical cord blood immediately after birth (6).  Maternal and cord blood was analyzed for four different forms of PCBs.  Prenatal exposure to dioxin was measured by analyzing milk samples collected during the second week of breast-feeding.  These breast-milk samples were analyzed for 17 dioxins and furans, and 24 different PCBs (6).  PCBs and dioxins measured in breast milk shortly after birth are considered an "index of maternal PCB and dioxin body burden" (1).  Body burden is the accumulated level of dioxin in the mothers's body.  These same breast milk samples were also used to estimate postnatal exposure, or exposure that results from breast-feeding.  This exposure was estimated by multiplying the levels of dioxins and PCBs measured in breast milk by the number of weeks of breast-feeding.  Current PCB exposure was measured in blood collected from the children at 42 months.  Current exposure measures the level of PCBs in the children's bodies.

The researchers in each of the studies used a statistical method called "multiple regression analysis," which evaluates the relationship between dioxin and PCBs levels and adverse health effects. They used this approach because of the unusual exposure situation. In studies of health effects, there is usually an "exposed" group which is compared to an "unexposed" group.  In this situation, the mothers were all exposed to the same general "background" level which may vary, but only slightly.  And, there are no controls who have had no exposure, because everyone is exposed to some dioxin in their food.   So the researchers looked to see if a correlation, or relationship, existed between the levels of dioxins and PCBs and a number of developmental, reproductive, and immunological effects.  In these studies, this means that as the "background" levels of dioxins and PCBs increased, the measured effect was greater.

In looking for these correlations, the Dutch researchers found that most of the effects were in children who were exposed before birth to dioxins and PCBs.  A few correlations were found in the children who were breast-fed.  The prenatal effects included reduced birth weight and reduced growth from birth through three months of age (7); delays in psychomotor development at three months (8); neurodevelopmental delays at two weeks (9) and at 18 months (10); alterations in thyroid hormones at birth and at three months (11); and alterations in immune status from birth to 42 months (12, 13).

In the most recent evaluation of the children with prenatal effects (at 42 months), the adverse neurological effects found at birth and at 18 months could not be detected (14).  However, now that the children were older, a decrease in cognitive function, as measured by a four point deficit in IQ, was measured between the children with the highest "background" levels of maternal PCBs  and the lowest "background" levels (3).  Other neurodevelopmental and behavioral effects found at 42 months in the children exposed prenatally included a decrease in high play activity, an increase in non-play activity, an increase in the errors of omission in the beginning of a task (4), and an increased prevalence of being withdrawn and depressed (5).

A few effects were found in the breast-fed children including delays in psychomotor development at seven months (8); alterations in thyroid hormones at three months (11); alterations in immune status as indicated by an increased prevalence of recurrent middle ear infections and decreased prevalence of allergic reactions to food, pollen, dust and pets at 42 months (12); and an increase in mean reaction times, a decrease in sustained attention, and an increase in hyperactive behavior at 42 months (4).

Adverse effects on neurological development were also reported in a study of children in the general Japanese population (15, 16).  In this study, exposure to "background" levels of dioxin and dioxin-like compounds in breast milk was associated with adverse immune effects (15) and altered thyroid function, including low levels of thyroid hormones essential for normal brain development (16).  Clinical studies have shown that children born with hypothyroidism (decreased levels of thyroid hormones) are at risk of mental retardation (17, 18, 19, 20).  Though there is considerable uncertainty about the impact of slight decreases in thyroid hormone levels during fetal and infant development, subtle neurological effects may occur.  In pre-term and low birth weight babies, low thyroid hormone in the first weeks of life is associated with higher than normal risk of neurological disorders, including the need for special education by age nine (21).

Effects on Developing Teeth

(Body text)Additional evidence of dioxin's effects on development comes from a study of Finnish children who, like the Dutch and Japanese children, did not have high levels of exposure to dioxin. In this study, Finnish children exposed to "background" levels of dioxin, as measured in breast milk, showed effects on tooth development (22, 23, 24).  Exposure to dioxin was estimated by multiplying the level of dioxin in breast milk by the length of breast feeding. Breast- fed children in the study suffered from hypo-mineralization defects of permanent teeth that included soft, discolored molars.  The authors found that as the concentration of dioxin in breast milk went up, the more frequent and more severe the tooth defects.  This finding is consistent with the timing of tooth mineralization which occurs during the first two years of life.

Teeth defects were also observed in the victims of rice oil poisonings in Yusho, Japan and Yu-Cheng, Taiwan.  In both cities, rice oil used for cooking was contaminated with PCBs and furans, and was widely distributed and consumed before the contamination was discovered. Exposed babies in both incidents had yellowish-brown tooth discolorations, teeth at birth, altered eruption of permanent teeth, and abnormally shaped tooth roots (25, 26).  The mothers of almost all of the affected babies had chloracne (a skin disorder associated with high level dioxin exposure), suggesting that the dose they were exposed to was quite high.  In addition, several children born near the dioxin-contaminated hazardous waste site at Love Canal, New York had teeth abnormalities such as double sets of teeth and teeth at birth (27).

In the Yusho and Yu-Cheng incidents, exposed children also had developmental delays, speech problems, behavioral difficulties, and impaired intellectual development (25, 28, 29 ).  The Yusho children had low birth weights and retarded growth (29).  The Yu-Cheng children also developed hearing loss and middle ear disease (30) and significantly reduced penis size (31).

In summary, there is growing body of evidence that dioxin exposure in the general population causes developmental and reproductive effects in children.  The effects on the development of the nervous system are more associated with exposure in the womb, while dental effects are more strongly associated with dioxin exposure from breast milk, a finding consistent with the timing of tooth mineralization in people.  These effects, including the small shifts in cognitive ability and alterations in thyroid levels, may be just the tip of the iceberg of our understanding of the impact of dioxin on the general population

In the Dutch, Japanese, and Finnish studies, the children or their mothers were not exposed to "high" levels of dioxin, such as those which might occur in the workplace or due to an accidental release.  In each study, the children and their mothers were exposed to "background" levels of dioxin, meaning that their exposure resulted primarily from the daily intake of dioxin in common foods.  This is important because it indicates that the daily intake of dioxin in food by the general population may be having a significant impact on our children's health.

All of the researchers in these studies refer to the dioxin exposures involved as "background" levels. This can be misleading because to many people, "background" implies an existing level of contamination about which nothing can be done.  This is clearly not the case with dioxin.  The "background" level of dioxin in our environment is not natural, it is the result of years of dioxin production by industry.  We know the sources of dioxin that contaminate our food and we know how we can stop dioxin production.  Americans have a choice.  We can protect public health by eliminating dioxin creation, or we can continue to allow dioxin to be created just to avoid burdening industry with the short term costs of elimination.

References

1.  Lanting, C.I. (1998) Effects of Perinatal PCB and Dioxin Exposure and Early Feeding Mode on Child Development. Thesis, Erasmus University, Rotterdam.

2.  Patandin, S. (1999a) Effects of Environmental Exposure to Polychlorinated Biphenyls and Dioxins on Growth
and Development in Young Children, A prospective follow-up study of breast-fed and formula- fed infants from birth until 42 months of age. Thesis, Erasmus University, Rotterdam.

3.  Patandin, S., Lanting, C.I., Mulder, P.G.H., Boersma, E.R., Sauer, P.J.J., and Weisglas- Kuperus, N. (1999b) "Effects of environmental exposure to polychlorinated biphenyls and dioxins on cognitive abilities in Dutch children at 42 months of age." Journal of Pediatrics 134: 33-41.

4.  Weisglas-Kuperus, N., Patandin, S., Berbers, G.A.M., Sas., T.C.J., Mulder, P.G.H., Sauer, P.J.J., and Hooijkaas, H. (1999) "Immunological effects of background expsoure to polychlorinated biphenyls and dioxins in Dutch toddlers." In: Effects of Environmental Exposure to Polychlorinated Biphenyls and Dioxins on Growth and Development in Young Children,  Patandin, S. Thesis, Erasmus University, Rotterdam, pp. 157-168, submitted for publication.

5.  Weisglas-Kuperus, N., Sas, T.C.J., Koopman-Esseboom, C., Zwan, C.W., van der Ridder, M.A.J., Beishuizen, A., Hooijkaas, H., and Sauer, P.J.J. (1995) "Immunological effects of background prenatal and postnatal exposure to dioxins and polychlorinated biphenyls in Dutch infants." Pediatric Research 38: 404-410.

6.  Koopman-Esseboom, C., Huisman, M., Weisglas-Kuperus, N., Van der Paauw, C.G., Tuinstra, L.G., Boersma, R., and Sauer, P.J. (1994) "PCB and Dioxin levels in plasma and human milk of 418 Dutch women and their infants. Predictive value of PCB congener levels in maternal plasma for fetal and infants's exposure to PCBs and Dioxins." Chemosphere 28: 1721- 1732.

7.  Patandin, S., Koopman-Esseboom, C., de Ridder, M.A.J., Weisglas-Kuperus, N., and Sauer, P.J.J. (1998) "Effects of environmental exposure to polychlorinated biphenyls and dioxins on birth size and growth in Dutch children." Pediatric Research 44: 538-545.

8.  Koopman-Esseboom, C., Weisglas-Kuperus, N., de Ridder, M.A., Van der Paauw, C.G., Tuinstra, L. G., and Sauer, P.J. (1996) "Effects of polychlorinated biphenyl/dioxin exposure and feeding type on infants' mental and psychomotor development." Pediatrics 97 (5): 700-706.

9.  Huisman, M., Koopman-Esseboom, C., Lanting, C. I., Van der Paauw, C.G., Tuinstra, L.G.M., Fidler, V., Weisglas-Kuperus, N., Sauer, P.J.J., Boersma, E.R., and Touwen, B.C.L. (1995) "Perinatal exposure to polychlorinated biphenyls and dioxins and its effects in neonatal neurological development." Early Human Development 41: 111-127.

10.  Huisman, M., Koopman-Esseboom, C., Lanting, C.I., Van der Paauw, C.G., Tuinstra, L.G., Fidler, V., Weisglas-Kuperus, N., Sauer, P.J., Boersma, E.R., and Touwen, B.C. (1995a) "Neurological condition in 18-month-old children perinatally exposed to polychlorinated biphenyls and dioxins." Early Human Development 43: 165-176.

11.  Koopman-Esseboom, C., Morse, D.C., Weisglas-Kuperus, N., Lutkeschipholt, I.J., van der Paauw, C.G., Tuinstra, L.G., Brouwer, A., and Sauer, P.J. (1994a) "Effects of dioxins and polychlorinated biphenyls on thyroid hormone status of pregnant women and their infants." Pediatric Research 36: 468-473.

12.  Lanting, C.I., Patandin, S., Fidler, V., Weisglas-Kuperus, N., Sauer, P.J.J., Boersma, E.R., and Touwen, B.C.L. (1998a) "Neurological condition in 42-month-old children in relation to pre- and postnatal exposure to polychlorinated biphenyls and dioxins." Early Human Development 50 (3): 283-292.

13.  Patandin, S., Veenstra, J., Mulder, P.G.H., Sewnaik, A., Sauer, P.J.J., and Weisglas- Kuperus, N. (1999c) "Attention and activity in 42-month-old Dutch children with environmental exposure to  polychlorinated biphenyls and dioxins." In: Effects of Environmental Exposure to Polychlorinated Biphenyls and Dioxins on Growth and Development in Young Children, Patandin, S. Thesis, Erasmus University, Rotterdam, pp. 123-142, submitted for publication.

14.  Patandin, S., Koot, H.M., Sauer, P.J.J., and Weisglas-Kuperus, N. (1999d) "Problem behavior in  Dutch children in relation to background polychlorinated biphenyl and dioxin exposure." In: Effects of Environmental Exposure to Polychlorinated Biphenyls and Dioxins on Growth and Development in Young Children, Patandin, S. Thesis, Erasmus University, Rotterdam, pp. 143-156, submitted for publication.

15.  Nagayama, J., Tsuji, H., Iida, T., Hirakawa, H., Matsueda, T., Okamura, K., Hasegawa, M., Sato, K., Ma, H.Y., Yanagawa, T., Igarashi, H., Fukushige, J., and Watanabe, T. (1998a) "Postnatal exposure to chlorinated dioxins and related chemicals on lymphocyte subsets in Japanese breast-fed infants." Chemosphere  37: 1781-7.

16.  Nagayama, J., Okamura, K., Iida, T., Hirakawa, H., Matsueda, T., Tsuji, H., Hasegawa, M., Sato, K., Ma, H.Y., Yanagawa, T., Igarashi, H., Fukushige, J., and Watanabe, T. (1998) "Postnatal exposure to chlorinated dioxins and related chemicals on thyroid hormone status in Japanese breast-fed infants." Chemosphere 37: 1789-93.

17.  Refetoff, S., Weiss, R.E., and Usala, S.J. (1993) "The syndromes of resistance to thyroid hormone." Endocrinology Reviews 14: 348-399.

18.  Rovet, J.F., Ehrlich, R.M., and Donner, E. (1993) "Long-term neurodevelopmental correlates of treatment adequacy in screened hypothyroid children." Pediatric Research 33: 91.

19.  Brucker-Davis, F., Skarulis, M., Grace, M., Hauser, P., Wiggs, E., and Weintraub, B.D. (1995) "Genetic and clinical features of 42 kindreds with resistance to thyroid hormone: The NIH prospective study."  Annals of Internal Medicine 123: 572-583.

20.  Hauser, P., McMillin, J.M., and Bhatara, V.S. (1998) "Resistance to thyroid hormone: Implications for neurodevelopmental research on the effects of thyroid hormone disruptors." Toxicology and Industrial Health 14 (1/2): 85-101, January-April.

21.  Den Ouden, A.L., Kok, J.H., Verkerk, P.H., Brand, R., and Verloove-Vanhorick, S.P. (1996) "The relation between neonatal thyroxine levels and neurodevelopmental outcome at ages 5 and 9 years in a national cohort of very preterm and/or very low birth weight infants."  Pediatric Research  39 (1): 142-145.

22.  Alaluusua, S., Lukinmaa, P-L., Torppa, J., Tuomisto, J., and Vartiainen, T. (1999) "Developing teeth as a biomarker of dioxin exposure." The Lancet 353: 206-207, Research Letters, January 16.

23.  Alaluusua, S., Lukinmaa, P-L., Vartiainen, T., Partanen, M., Torppa, J., and Tuomisto, J. (1996)
"Polychlorinated dibenzo-p-dioxins and dibenzofurans via mother's milk may cause developmental defects in the child's teeth." Journal of Environmental Toxicology and Pharmacology 1: 193-197.

24.  Alaluusua, S., Lukinmaa, P-L., Koskimies, M., Pirinen, S., Holtta, P., Kallio, M., Holttinen, T., and Salmenpera, J. (1996a) "Developmental dentin defects associated with long term feeding."  European Journal of Oral Science 104: 493-497.

25.  Rogan, W.J., Gladen, B.C., Hung, K-L., Koong, S-L., Shih, L-Y., Taylor, J.S., Wu, Y-C., Yang, D., Ragan, B., and Hsu, C-C. (1992) "Congenital poisoning by polychlorinated biphenyls and their contaminants in Taiwan." Science 241: 334-336, July, 15.

26.  Kuratsune, M. (1989) "Yusho, with reference to Yu-Cheng." In: Halogenated Biphenyls, Terphenyls, Napthalenes, Dibenzodioxins and Related Products. Kimbrough, R.D. and Jensen, A.A. (eds.) 2nd ed. New York: Elsevier Science Publishers, pp.381-400.

27.  DOH (1981) Love Canal, A Special Report to the Governor and Legislature. New York State Department of Health, September.

28.  Hsu, C-C., Yu, M-L.M., Chen, Y-C.J., Guo, Y-L.L., and Rogan, W.J. (1994) "The Yu-cheng Rice Oil Poisoning Incident." In: Dioxins and Health, Schecter, A. (Ed.). New York: Plenum Press, pp. 661-684.

29.  Masuda, Y. (1994) "The Yusho Rice Oil Poisoning Incident." In: Dioxins and Health, Schecter, A., (ed.) New York: Plenum Press, pp. 633-684.

30.  Chao, W-Y., Hsu, C-C., and Guo, Y.L. (1997) "Middle-ear disease in children exposed prenatally to polychlorinated biphenyls and polychlorinated dibenzofurans." Archives of Environmental  Health  52: 257-262.

31.  Guo, Y.L., Lai, T.J., Ju, S.H., Chen, Y.C., and Hsu, C.C. (1993) "Sexual developments and biological findings in Yu-cheng children." Organohalogen Compounds 14: 235-237.

Originally published in Everyone's Backyard, Vol. 17, No. 4 (Winter 1999-2000)

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