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Valid reasons to link autoimmunity and environment? Explain.




Given what you read in the above article, do you think there are valid reasons to link autoimmunity and environment? Explain.;Do these links make sense from an immunological perspective? Give specific examples in your answer.;What other explanation can you think of to explain the increases in autoimmunity seen in the human population?;Attachment Preview;article.pdf Download Attachment;Correspondence;should include UV exposure, even absent;specific FDA requirements.;Our resin data (resins P1. P2, P3, P4;P19, and P18) cited by Kelce and Borgert;came from at least three replications of stress?;ing, extraction, and EA assays. As described;in our ?Methods? and ?Supplemental;Material,? the assay variance was very small;SEs were typically smaller than the diameter;of the data points of the graphed means.;The whole series of 49 assays was repeated;only once, but no extract exhibited EA, more;recent extracts of the same plastics confirm;our original results.;Kelce and Borgert noted that colorants are;?embedded? in plastics. However, ?bound?;colorants in plastic compounds can and do;readily leach from plastics. They are additives;which?like most additives?are only rarely;chemically bound to polymers. Hence, con?;cerns about all additives are warranted because;any can leach from a plastic product.;Regarding broader issues, the objective;of our paper was to quantify the prevalence;of xeno? strogen release from commonly used;e;plastic products. These data are significant in;part to help assess the risk of such products;to human health and environmental con?;tamination. Kelce and Borgert cite Charles;et al. (2007), who examined some inter?;actions between a small set of phyto? strogens;e;and xeno? strogens. The limited negative;e;results of that study have been contradicted;by dozens of other studies (e.g., Patisaul and;Jefferson 2010). However, our objective was;not to establish definitive links between pub?;lic health issues, environmental pollution;and exposure to xenoestrogens. This relation?;ship is an active research area, and it will take;many years to obtain definitive answers.;Kelce and Borgert?s concerns about the;paucity of epidemiological data correlating;EA exposure via use of plastics with adverse;human health effects is analogous to the longstanding controversy for tobacco, which is;now highly regulated, largely because increas?;ing numbers of epidemiological studies;correlated smoking with heart disease and;lung cancer. For decades, it was common to;hear tobacco industry spokes? ersons argue;p;that ?[epidemiological] correlation does not;mean causation? and demand that molecu?;lar, cellular, and/or systemic mechanisms be;extensively demon? trated before any action;s;regulatory or otherwise, be taken. One rarely;hears spokespersons for the chemical and;plastics industry make this argument for;release of chemicals having EA from plastics;because the mechanisms by which tobacco;has its effects are still much less well known;compared to mechanisms by which chemi?;cals having EA produce adverse health and;environ? ental effects. Instead, we hear;m;?Where are the epidemiological correlations??;Environmental Health Perspectives? ??;Those correlations are fewer (but not non?;existent) than for tobacco at this relatively;young stage of the field, but the number of;such publications is rapidly increasing. In;the meantime, our study and hundreds to;thousands of other in vitro studies demon?;strate that chemicals having EA have eas?;ily measurable effects on all sorts of human;cells (including MCF-7 cells). Most scientists;in this field believe that such results suggest;adverse health effects in humans and that;as such data continue to be gathered, these;correlations will become as compelling as did;those for the impact of tobacco smoking on;public health.;Legislators, consumers, manufacturers;and scientists must judge current industry;practices in this area based on available data.;Reasonable people can differ. The American;Chemistry Council takes the position that;until definitive studies consistently show;health and environmental hazards from;chemi? als with EA leaching from plastic;c;products, no industry action need be taken.;We disagree. Plastic items are essential con?;sumer products, but we argue that they need;to be made safer. Our most recent data show;that there is very little extra expense to pro?;duce safer plastics that do not leach chemi?;cals having EA, that is, it costs very little at;this time to avoid a potential health risk.;C.Z.Y. is employed by, and owns stock in;CertiChem (CCi) and PlastiPure (PPi). S.I.Y.;and D.J.K. are employed by PPi. V.C.J. has;no financial interests in CCi or PPi, but he;was principal investigator for a subcontract at;Northwestern Medical School to help develop the;MCF-7 assay on NIH grant P30 CA051008;awarded to CCi. G.D.B. owns stock in and is;the founder and chief excutive officer of CCi and;the founder and chief scientific officer of PPi. All;authors had freedom to design, conduct, interpret, and publish research uncompromised by;any controlling sponsor.;Chun Z. Yang;George D. Bittner;CertiChem Inc.;Austin, Texas;Stuart I. Yaniger;Daniel J. Klein;PlastiPure Inc.;Austin, Texas;V. Craig Jordan;Lombardi Comprehensive Cancer Center;Georgetown University Medical Center;Washington, DC;References;Charles GD, Gennings C, Tornesi B, Kan HL, Zacharewski TR;Gallapudi BB, et al. 2007. Analysis of the interaction of;phytoestrogens and synthetic chemicals: an in vitro/;in vivo comparison. Toxicol Appl Pharmacol 218:280?288.;FDA (Food and Drug Administration). 2002, 2007. Guidance;for Industry: Preparation of Premarket Submissions;volume 119 | number 9 | September 2011;for Food Contact Substances: Chemistry Recom?;menda? ions. Available:;t;GuidanceComplianceRegulatoryInformation/;GuidanceDocuments/FoodIngredientsandPackaging/;ucm081818.htm [accessed 10 August 2011].;Patisaul HB, Jefferson W. 2010. The pros and cons of phyto?;estrogens. Front Neuroendocinol 31(4):400?419;doi:10.1016/j.yfme.2010.03.003 [Online 27 March 2010].;Wagner M, Oehlmann J. 2010 Endocrine disruptors in bottled;mineral water: estrogenic activity in the E-screen. J Steroid;Biochem Mol Biol, doi:10.1016/j.jsbrnb.2010.10.007 [Online;2 November 2010].;Yang CZ, Yaniger SI, Jordan VC, Klein DJ, Bittner GD. 2011.;Most plastic products release estrogenic chemicals;a potential health problem that can be solved. Environ;Health Perspect 119:989?996, doi:10.1289/ehp.1003220;[Online 2 March 2011].;Environmental Factors;Develop Different Patterns;of Immune Disease;doi:10.1289/ehp.1104043;I read with interest the article by Schmidt;(2011) on the sprawling explosion of auto?;immune diseases and its link to environ? ental;m;exposure. Schmidt (2011) summarized the;problematic state of the field: Systemic auto?;immune diseases are common but thought;rare, their clinical identification is far from the;medical school description, and they continue;to be identified as an auto? ntibody?target?;a;manifestation scheme. Experience shows that;a patient develops different auto? ntibodies;a;through the lifespan, with different clinical;patterns within each phase, deeper investiga?;tion shows that organ auto?mmune disease is;i;in fact systemic. Likewise, allergy, food intol?;erance, cancer, and immuno? eficiency (all;d;broad diseases that are immune in nature);cross and share auto?mmunity. This suggests;i;that immature immune systems are promoted;and prevented from natural selection in the;era of anti? iotics, but they pay the cost of fos?;b;tered health dysfunctions or diseases exposed;to the current complex hostile environment.;I noticed this complex scenario in a sur?;vey of 22 patients reporting sick building;syndrome (Blasco 2011). Although reported;data was limited to auto?mmune cases and;i;the involved substances were not yet identi?;fied, I found that the same environment trig?;gered and worsened other immune dis? rders.;o;The health of two patients with asthma;inexplicably worsened when they started to;work in the building. One patient developed;gyneco?ogical cancer, another patient, who;l;had a past history of Hodgkin?s lymphoma;developed chronic fever and fatigue again;that lasted 3 years, until she was relocated.;Some of the patients reported new adult onset;of clinical intolerance of milk or other foods;and one patient was positive in a breath test;for lactose intolerance. A review of family;histories revealed that in 20% of the patients;more than one direct relative was affected by;cancer. Personnel records showed that allergy;A 379;Correspondence;was present in 59% of the patients, recurrent;infections during childhood were common;20% required amigdalectomy. One patient;suffered rheumatic fever, one patient had not;been effectively immunized after repeated;hepatitis vaccines, and another had defective;CD4 and suffered recurrent pneumo? occal;c;infections.;It would be surprising if these illnesses;did not share a common root in the immune;system. Schmidt (2011) underlined rising;prevalence rates of auto?mmunity and dis?;i;cussed causes. I believe that this trend is rele?;vant in general to immune disorders because;of different reactions within the same scope;of lymphocyte dysfunction in response to;our new aggressive environment.;The author declares that he has no actual or;potential competing financial interests.;Luis M. Blasco;UARH;Hospital Marqu?s de Valdecilla;Santander, Spain;E-mail:;References;Blasco LM. 2011. Sick building syndrome and autoimmunity.;Lupus 20:544?546.;Schmidt CW. 2011. Questions persist: environmental factors in autoimmune disease. Environ Health Perspect;119:A248?A253.;Dietary Intervention and DEHP;Reduction;doi:10.1289/ehp.1103852;Rudel et al. (2011) reported a surprising;reduction in metabolites of bis(2-ethyl? exyl);h;phthalate (DEHP) in their dietary interven?;tion study, considering that?to the best of;the industry?s knowledge?the plasticizer is;no longer used in the food packaging prod?;ucts that the authors removed from the sub?;jects? dietary routine. Although we question;the public health significance of a potential;reduction of a few micrograms per liter of;DEHP metabolites, we initially saw the study;as having the potential to improve our under?;standing of how low-level exposure to DEHP;suggested by the presence of the metabolites;may be occurring. Unfortunately, in review?;ing the Rudel et al. analysis more thoroughly;we were disappointed.;The 56% reduction in mean levels sug?;gested by Rudel et al. (2011) is based on the;concentration of DEHP metabolites?before;correcting for creatinine levels. With little;more than a sentence, Rudel et al. dismissed;the accepted practice of correcting for crea?;tinine levels to account for the substantial;variability in an individual?s urine output.;They suggested that such adjustment may;?bias associations between urine metabo?ite;l;concentrations and age or sex? (Rudel et al.;A 380;2011) without explaining that the correction;is widely used in urinary bio? onitoring (by;m;the Centers for Disease Control and most;others) to improve the comparability of meas?;ure? ents across individuals.;m;To their credit, Rudel et al. (2011) did;conduct a compari? on of the creatinines;adjusted levels of DEHP metabolites and;found no statistically significant difference in;the mean levels of two of the three metabo?;lites before and after dietary intervention.;The authors did not report the change in;the adjusted levels of the third metabolite in;the article.;The authors also did not address the;variability in preintervention levels among;the study participants. The presence of two;individuals with very high metabolite levels;clearly skewed the mean value upward and;consequently, exaggerated the significance of;the intervention. Although Table 2 of Rudel;et al. (2011) provides the minimum, mean;and maximum values, the variability is best;seen in their Supplemental Material, Figure 3;(doi:10.1289/ehp.1003170), and on Silent;Spring Institute?s web site (Silent Spring;Institute 2011). It is unfortunate that Rudel;et al. (2011) chose not to address the vari?;ability in their article?and a bit surprising?;because the post? ntervention increase in;i;DEHP metabolites was significantly lower;than the reported decrease (16% versus 56%).;The author is employed by the American;Chemistry Council to represent the manufacturers;of phthalates, including DEHP.;Stephen P. Risotto;American Chemistry Council;Washington, DC;E-mail:;Reference;Rudel RA, Gray JM, Engel CL, Rawsthorne TW, Dodson RE;Ackerman JM, et al. 2011. Food packaging and bisphenol A;and bis(2-ethylhexyl) phthalate exposure: findings from a;dietary intervention. Environ Health Perspect 119:914?920;doi:10.1289/ehp.1003170 [Online 30 March 2011].;Silent Spring Institute. 2011. Phthalate Levels Decline during;3-Day Fresh Food Diet. Available: http://www.silentspring.;org/images/our_research/DEHP_results.jpg [accessed;12 August 2011].;Dietary Intervention and DEHP;Reduction: Rudel et al. Respond;doi:10.1289/ehp.1103852R;Steven Risotto, representing phthalate;manufacturers for the American Chemistry;Council (ACC), commented on our study;that found a 3?day diet with limited food;packaging reduced participants? average;bis(2-ethyl? exyl) phthalate (DEHP) expo?;h;sure by > 50% (Rudel et al. 2011).;Risotto?s statement that creatinine adjust?;ment by normalization is accepted practice;is misleading. Creatinine normali? a? ion is;z t;appropriate in a longitudinal study if the;daily creatinine excretion of the partici?;pants remains approximately constant. That;assumption is not reasonable in a dietary;intervention because short-term changes in;diet can strongly influence creatinine levels;(Kesteloot and Joossens 1993). In our article;(Rudel et al. 2011), we addressed urinary;dilution by including creatinine as a vari?;able in the mixed-effects model that estimates;exposure reduction from the intervention, as;currently recommended by researchers at the;Centers for Disease Control and Prevention;(Barr et al. 2005). Our analysis showed sig?;nificant decreases of 53?56% in the three;DEHP metabo?ites. Because creatinine nor?;l;malization is common, we also included nor?;malized results. Creatinine levels dropped;significantly during the intervention, indicat?;ing that creatinine normalization artificially;reduced the observed change. Nonetheless;results showed a 42?45% decrease in all;three DEHP metabolites, the decrease was;statistically significant for the most abun?;dant metabolite, MEHHP (mono-(2-ethyl5-hydroxy? exyl) phthalate).;h;Risotto also questions whether DEHP;reductions are attributable to two individu?;als with high initial exposures. However, we;reported the decreases in geometric means;which are not strongly influenced by a;few high values. After removing these two;participants, we still observed decreases of;37?42% in the geometric means of DEHP;metabolites, and reductions in the two most;abundant metabolites remain statistically sig?;nificant. Removing participants with high;pre?ntervention exposures is appropriate if;i;an unknown exposure may have covaried;with the inter? ention, but because the two;v;highest exposures were in different families;such confounding seems unlikely.;As to why DEHP metabolite levels;dropped during the intervention but did;not increase significantly after the interven?;tion?as discussed in detail in our article;(Rudel et al. 2011)?the discrepancy may be;attributable to the different-length ?washout;periods? (~ 48 hr between the beginning of;the intervention and the first intervention;urine sample, and ~ 36 hr between when;participants resumed their regular diet and;the first post?ntervention urine sample).;i;Risotto questions the public health;signifi? ance of our observed reduction in;c;DEHP exposure. However, DEHP exposure;levels in our study (Rudel et al. 2011)?and;in the U.S. population?are similar to or;higher than those recently reported to exceed;health guidelines. Koch et al. (2011) found;that 5 of 108 children studied had daily;DEHP intakes in excess of the current U.S.;Environmental Protection Agency reference;dose, and 25% exceeded the tolerable daily;? ?? Environmental Health Perspectives


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