CCA-Treated Wood and Down Syndrome 

LAURETTE JANAK
Submission to the EPA panel on child health risk from CCA wood 19aug02

Laurette Janak
7185 Liebler Rd. 
Colden, NY   14033 
(716)941-4622 
laurettejanak@cs.com 

Public Information and Records Integrity Branch (PIRIB)
Information Resources and Services Division (7502C)
Office of Pesticide Programs (OPP)
Environmental Protection Agency
Pennsylvania Ave., NW
Washington DC 20460 USA

August 19,2002

Re: CCA-treated wood; docket ID OPP-2002-0147

To Whom it may concern: I have a daughter with Down syndrome (DS). Her genetics may have set the stage for cancer but I believe her chronic exposure to CCA lumber may have been the trigger to her leukemia. DS children have oral fixations that exceed those of normal children; they experience their world through their tongues. I was unaware that our home deck contained arsenic. Naturally I would stop my daughter from her habitual chewing on the railings of the deck when I saw her doing so; however, I was not overly concerned about it. After all, I reasoned, how harmful can wood be???? It was through an acutely toxic reaction to CCA wood that I learned about the chronic nature of her exposures. To improve the appearance of our unsealed deck, we sanded it and thus exposed our daughter to the arsenic laced saw dust which she consumed orally. It took approximately 2 months from the time we sanded until we got an accurate diagnosis of arsenic poisoning. Our deck was tested and came in at 1680 ppm of arsenic. It was at this point that I learned of the immense ignorance surrounding childhood exposure to arsenic through CCA treated lumber.

OVERVIEW

Toxicology studies should take into consideration those segments of the population which are the most sensitive. There are several subgroups which have been overlooked with regards to CCA exposure and toxicity. I will briefly go over the chemistry that effects one special subset of children and predisposes them to both the neurological and carcinogenic properties of CCA treated wood. This group and others similarly effected should be strongly considered in the design of any studies used to determine the deleterious effects of CCA exposure.

DOWN SYNDROME CHEMISTRY

Roughly 1 in 500 births results in the live birth of an infant with Trisomy 21 or Down syndrome (DS). It has been shown that children with DS have significantly reduced plasma glutathione levels. (1) The gene for Cu-Zn superoxide dismutase (SOD) is coded on chromosome 21 which is overexpressed in DS. Such overexpression results in increased oxidative stress (an increase in ROS) and an overproduction of hydrogen peroxide (H2O2) in DS individuals.(2-4) To further complicate matters, the gene for cystathionine beta-synthase (CBS) is also located on chromosome 21 and is therefore also overexpressed in DS. The CBS overexpression causes a functional folaate deficiency with a decrease availability of folate for the de novo synthesis of purines and the pyrimidine thymidylate, an increase production of cysteine and alterations in the methylation cycle with significantly decreased levels of S-adenosylmethionine (SAM).(1) Excessive copper levels have also been reported in DS.(5)

MECHANISMS OF ARSENIC TOXICITY

Recent research into the toxic effects of arsenic have revealed that exposure to this environmental toxin has a pro-apoptoic effect on lymphoid cells. The mononuclear cells from children who have been chronically exposed to arsenic have a high basal rate of apoptosis. (6) In order to understand the mechanism by which arsenic induces apoptosis, I looked at the current medical literature and the use of arsenic trioxide (ATO) for the treatment of cancer. Such treatments utilize the controlled use of ATO to induce apoptosis in cancer cells. Sensitivity to arsenic induced apotosis was found to be "inversely related to their intracellular glutathione (GSH) and intensity of GSH synthesis." (7) Cells which were resistant to apoptosis where restored to sensitivity by utilizing GSH depleting chemicals. An additional mechanism for the induction of apoptosis may be mediated through the production of reactive oxygen species (ROS). The use of ATO "increased cellular content of reactive oxygen species (ROS), especially hydrogen peroxide (H2O2), and the antioxidant N-acetyl-L-cysteine completely suppressed As2O3 induced apoptosis." "Incubation of the cells with catalase resulted in significant suppression of As₂O₃ -induced apoptosis."(8) NAC of course is a precursor to GSH while catalase is able to help deal with the increase production of H2O2. Thus it is clear that both the oxidative status and the inherent level of GSH in an individual are important mediators for sensitivity to the toxic effects of arsenic.

ADDITIONAL FACTORS IN CCA WOOD

Since CCA treated lumber also contains chromium it is important to note the significance of GSH with respect to chromium toxicity (9,10) so that one can understand the synergistic toxic effect of their combination. Likewise, consideration should be given to the synergistic effect of increased exposure to copper and individuals such as DS persons who already have elevated copper. To date, I have not found any published medical literature which looks at the combined toxic effect of copper, arsenic and chromium. Studies that attempt to look at the toxicity of CCA treated wood by investigating arsenic alone, must be considered poor science!

CCA EXPOSURE IN DS

Due to the lowered GSH levels in DS, one can clearly see how such individuals would have increased sensitivity to arsenic and chromium which further deplete GSH while simultaneously increasing the production of ROS and H2O2 beyond the problematic level already existing in DS. In an animal model of DS "a GSH level which is decreased under a specific threshold by increased consumption, reduced synthesis or lack in precursor contributes to cell loss and neurodengenration in Down syndrome." (11) The inability to clear heavy metals may predispose to the early onset of Alzheimer¹s disease (AD) in aging DS persons by further depleting GSH and increasing oxidative stress.

METHYLATION AND GENETIC POLYMORPHISMS RELATING TO METALS

An additional factor to consider is the methylation status of an individual. It has been proposed that variations in the activity of methylene-tetrahydrofolate reductase (MTHFR) enhance the toxic effects of arsenic (12). Support for this line of thinking come from findings that show "folic acid protects SWV/Fnn embryo fibroblasts from sodium arsenite and DMA cytotoxicity in a dose-dependent manner." (13) Recent data has found elevated plasma homocysteine (Hcy) in mothers who give birth to DS infants. (14,15) The elevated Hcy can in part be explained by common polymorphisms in MTHFR and methionine synthase reductase (MTRR). Mothers of DS individuals have an elevated risk of developing Alzheimer's disease (AD) as they age.(16) Several new studies have determined elevated Hcy to be a risk factor for AD. (17,18) Treatment with folate has been shown to increase GSH while lowering Hcy and oxidative stress. (19) Taken together, these facts may point to an additional at risk population when exposed to GSH depleting metals such as those found in CCA lumber.

GSH depleting agents cause a diversion of folate away from the biosynthesis of purines and the pyrimidine thymidylate which is needed for DNA repair(20). "Thus alterations in gene expression could result from a high dose and/or prolonged exposure to GSH-depleting agents, e.g. medications, chemotherapeutic agents and environmental toxins." (21) This leaves individuals who have altered folate or GSH levels due to polymorphisms at increased risk of cancer upon exposure to agents such as those found in CCA wood. Therefore, the risk of cancer in DS individuals who are exposed to environmental toxins may exceed that of non-trisomic individuals. In fact there is a dramatic increase incidence of leukemia associated with DS. (22,23) A multitude of current research has implicated disruptions in the folate cycle with the onset of leukemia. (24-28) Arsenic and chromium both cause disruptions in these same pathways thus leukemia should now be considered among the cancers induced by environmental exposure to arsenic. The bone marrow suppressive qualities of this toxin are well established.

CLOSING SUMMARY

1.) Any study on the toxic effects of exposure to CCA treated lumber, should include the synergistic effects of the arsenic along with the chromium and copper. 2.) Subpopulations that have increased sensitivity to environmental exposures should be investigated instead of assuming that exposures impact all people equally. Concurrent exposures to other heavy metals such as mercury or lead, would increase the sensitivity to CCA through continual depletion of GSH. 3.) The incidence of leukemia associated with exposure to arsenic warrants thorough investigation. 4.) Public education is severely limited on how to handle CCA treated lumber. This is evidenced by my personal story and the stories of many others whom I have personally heard from experiencing exposure problems. 5.) Lastly, the public will not tolerate lies, deceptions, or "junk science" that cover for industry.

REFERENCES

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4. Midorikawa K, Kawanishi S. Superoxide dismutases enhance H2O2-induced DNA damage and alter its site specificity. FEBS Lett. 2001 Apr 27;495(3):187-90

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13. Ruan Y, Peterson MH, Wauson EM, Waes JG, Finnell RH, Vorce RL. Folic acid protects SWV/Fnn embryo fibroblasts against arsenic toxicity. Toxicol Lett. 2000 Nov 20;117(3):129-37.

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17. Kruman II, Kumaravel TS, Lohani A, Pedersen WA, Cutler RG, Kruman Y, Haughey N, Lee J, Evans M, Mattson MP. Folic acid deficiency and homocysteine impair DNA repair in hippocampal neurons and sensitize them to amyloid toxicity in experimental models of Alzheimer's disease. J Neurosci. 2002 Mar 1;22(5):1752-62.

18. Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D'Agostino RB, Wilson PW, Wolf PA. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med. 2002 Feb 14;346(7):476-83.

19. Mayer O Jr, Simon J, Rosolova H, Hromadka M, Subrt I, Vobrubova I. The effects of folate supplementation on some coagulation parameters and oxidative status surrogates. Eur J Clin Pharmacol. 2002 Apr;58(1):1-5.

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21. Lertratanangkoon K, Wu CJ, Savaraj N, Thomas ML. Alterations of DNA methylation by glutathione depletion. Cancer Lett. 1997 Dec 9;120(2):149-56.

22. Reynolds P, Von Behren J, Elkin EP. Birth characteristics and leukemia in young children. Am J Epidemiol. 2002 Apr 1;155(7):603-13.

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24. Morgan GJ, Smith MT. Metabolic enzyme polymorphisms and susceptibility to acute leukemia in adults. Am J Pharmacogenomics. 2002;2(2):79-92.

25. Skibola CF, Smith MT, Hubbard A, Shane B, Roberts AC, Law GR, Rollinson S, Roman E, Cartwright RA, Morgan GJ. Polymorphisms in the thymidylate synthase and serine hydroxymethyltransferase genes and risk of adult acute lymphocytic leukemia. Blood. 2002 May 15;99(10):3786-91.

26. Crott JW, Mashiyama ST, Ames BN, Fenech MF. Methylenetetrahydrofolate reductase C677T polymorphism does not alter folic acid deficiency-induced uracil incorporation into primary human lymphocyte DNA in vitro. Carcinogenesis. 2001 Jul;22(7):1019-25.

27. Wiemels JL, Smith RN, Taylor GM, Eden OB, Alexander FE, Greaves MF. Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and risk of molecularly defined subtypes of childhood acute leukemia. Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):4004-9.

28. Krajinovic M, Labuda D, Sinnett D. Childhood acute lymphoblastic leukemia: genetic determinants of susceptibility and disease outcome. Rev Environ Health. 2001 Jul-Sep;16(4):263-79. Review.