May 12, 2008

Attention: Docket ID Numb er EPA–HQ–OPPT–2008–0273 Environmental Assist ance Division (7408M) Office of Pollution Prevention and Toxics Environmental Protection Agency 1200 Pennsylvania Ave., NW Washington, DC 20460–0001 Re: Comments on Mr. Michael Dochniak Section 21 TSCA Petition Dear Sir or Madam: The Rubber Manufacturers Association (“RMA”) submits the following comments on the petition from Michael J. Dochni ak filed pursuant to Section 21 of the Toxic Substance Control Act on March 6, 2008, requesti ng that the Environmental Protection Agency (“EPA”) “establish regulations prohibiting the use and distribution in commerce of Hevea brasiliensis natural rubber latex (NRL) adhesives having a total protein content greater than 200 micrograms per dry weight of latex based on the American Society for Testing and Material’s method ASTM D1076–06 (Category 4)” because “implementation of an EPA regulation may affect the incidence and prevalence of latex al lergy and allergy-induced autism in neonates.” 1 (“Dochniak Petition”)

1 EPA, Hevea brasiliensis Natural Rubber Latex Adhesives; TSCA Section 21 Petition; Notice of Receipt, 73 Fed. Reg. 22,368 (April 25, 2008) [EPA–HQ–OPPT –2008–0273; FRL–8361–3] (“Dochinak Petition Fed. Reg. Notice”).Docket ID Number EPA–HQ–OPPT–2008–0273 May 12, 2008 Page 2
RMA is a not-for-profit national tr ade association, which represents approximately 80 member companies who manuf acture goods made with rubber. A number RMA members use and di stribute in commerce Hevea brasiliensis natural rubber latex adhesives and some members produce Hevea brasiliensis natural rubber latex that is used in the manufacture of adhesives. If EP A promulgates a regulation consiste nt with the relief requested in the Dochniak Petition, these companies would be banned from selling their products in the United States. Therefore, RMA members have a significant interest in this proceeding. In summary, autism can be a severe medi cal condition that presents significant obstacles to the individual w ho have the condition and daunting challenges to the relatives and friends of these individuals. Rightfully, th e Federal government a nd private groups support research into this condition. However, the al legations in the Dochni ak Petition that claim exposure to natural latex rubber allergens cause autism are not supported by any peer reviewed scientific article or any original data. The allega tions also do not follow the criteria for reviewing scientific information provided in EPA’s Assessm ent Factors Document. Therefore, there is no unreasonable risk to health. Finally, the relie f sought (a complete ban) is not the least burdensome requirement, as required by TSCA. Our comments are organized as follows. Section I provides a brief background on the Petition, including a discussion of the requirements of TSCA Section 21. Section II summarizes the weight of scientific opinion c oncerning the allegation and the reasons that EPADocket ID Number EPA–HQ–OPPT–2008–0273 May 12, 2008 Page 3
should reject the Petition. Sec tion III summarizes the lack of ev idence linking latex exposure to autism.



### I. BACKGROUND ON THE PETITION A. Introduction EPA received the Dochniak Petition on March 6, 2008 and published notice of the petition on April 25, 2008. Subsection B descri bes the basic TSCA statutory framework. Subsection C discusses the Secti on 21 petition process. Subsecti on D summarizes the scientific factors that EPA uses in assessing such a petition. B. The Basic TSCA Framework The Toxic Substances cont rol Act, 15 U.S.C. §§ 2601-2629, was first enacted in 1976. The overall purpose of the Act was to es tablish a comprehensiv e national system for “evaluating and regulating chemical substances to protect against unreas onable risks to human health and to the environment.” Chemical Mfrs. Ass’n v. EPA , 359 F.2d 977, 979 (D.C. Cir. 1988); Ausimont U.S.A., Inc. v. EPA, 838 F.2d 93, 95 (3d cir. 1988). Section 6 of the Act authorizes EPA to impose controls on the produc tion, distribution, use, an d disposal of toxic substances if the evidence shows that such activit y “presents or will present an unreasonable risk of injury to health or the environment.” 15 U.S.C.§ 2605(a). Regulator y controls may include labeling guidelines, notice requirements, or rest rictions on the production and distribution of toxic substances. Id . Section 4 of the Act authorizes EP A to require testing of chemical substances or mixtures if it find that such substa nces “may present an unr easonable risk of injuryDocket ID Number EPA–HQ–OPPT–2008–0273 May 12, 2008 Page 4

to health or the environment” and that “there are insufficient data and experience” upon which to predict the effects of such s ubstances. 15 U.S.C. § 2603(a)(1)(A) . Lastly, section 8 authorizes EPA to impose reporting and r ecord-keeping requirements on the manufacturers and processors of toxic substances. 15 U.S.C. § 2607; see also Environmental Defense Fund v. Thomas , 657 F. Supp. 302, 304 (D.D.C. 1987). While seeking to eliminate “unreasonab le risk,” Congress directed EPA to exercise its authority “in such a manner as not to impede unduly or create unnecessary economic barriers to technical inno vation.” 15 U.S.C. § 2601(b)(3). EPA must carry out the provisions of the Act in a “reasonable and pr udent manner” and must “consider the environmental, economic, and social impact of any action” taken. 15 U.S.C. § 2601(c); see also Ausimont U.S.A., Inc. v.
EPA , 838 F.2d at 95. 2 If EPA issues rules governing the production or disposal of any toxic substance, it must consider th e “reasonably ascertainable econo mic consequences” of potential regulatory restrictions. 15 U.S.C. § 2605(c)(1)(D). The agency must also select “the least burdensome requirements” that would be effective. 15 U.S.C. § 2605(a); see also 122 Cong. Rec. 32,828 (1976). 3

2 Congress required EPA to carefully consider the costs and benefits of any regulatory restrictions imposed under the Act. See S. Rep No. 698, 94 th Cong. 2d Sess. 13 (1976) (“It is important to note that in the testing and key regulatory provisions of the legislation, it is specifically required that the Administrator evaluate the risks and benefits of his actions before talking regulatory action. Thus, costs are not to be incurred unless they are offset by benefits of at least the same magnitude.”); 122 Cong. Rec. 32,852 (1976); see also 15 U.S.C. § 2605(c)(1).

3 As EPA has stated, a “basic principle embodied in TSCA is that the Agency must adopt regulatory requirements which impose the smallest social and economic burden possible . . . .” Guidance for Petitioning the Environmental Protection Agency Under Section 21 of the Toxic Substances Control Act, 50 Fed. Reg. 46,825, 46,826 (1985) (“ Petition Guidance”).Docket ID Number EPA–HQ–OPPT–2008–0273 May 12, 2008 Page 5
In addition to authorizing EPA to regul ate the use and dis posal of all toxic substances, the Act imposes specific restricti ons on the use and dispos al of polychlorinated biphenyls and asbestos. C. TSCA Section 21 Petition Process TSCA specifically provides that “[a]ny pe rson may petition the Administrator to initiate a proceeding for the issuance, amendment, or repeal of a rule under Sections 2603, 2605, or 2607 . . . .” 15 U.S.C. § 2620(a). Such a peti tion “shall set forth the facts” justifying the requested relief. EPA may “hold a public he aring or may conduct such investigation or proceeding” as may be necessary. 15 U.S.C. § 2620(b)(2). EPA must either grant or deny the petition within 90 days of its filing. 15 U.S.C. § 2620(b)(3). 4 Section 21 itself does not impose a legal standard for the issuance of relief. 5 The agency’s decision, therefore, must be based upon the fundamental policies underlying the entire Act. EPA’s regulatory approach must be designed to eliminate any “unreasonable risk” using the least burdensome and least costly means available. 15 U.S.C. §§ 2601( b),(c), 2605(a), (c), (e). If EPA grants a citizens petition, it must promptly initiate a proceeding under the appropriate section. 15 U.S.C. § 2620(b)(3). If EPA denies the petition, it must publish its reasons for the denial in the Federal Register. Id . Where the petition is denied, or where EPA

4 The “remedies under this section shall be in addition to and not in lieu of, other remedies provided by law.” 15 U.S.C. § 2620(b)(5).

5 EPA has issued “guidance” on section 21 petitions, but this guidance is non-binding and is mainly procedural in nature. See Petition Guidance, supra , note 3. In its guidance, however, EPA must “balance the benefits derived from risk reduction against the social and economic costs” of regulation. Id . at 46,826.Docket ID Number EPA–HQ–OPPT–2008–0273 May 12, 2008 Page 6
fails to act on the petition within the prescribed 90-day period, the petitioner may seek judicial review in federal district court. 15 U.S.C. § 2620(b)(4); Environmental Defense Fund v. Thomas , 657 F. Supp. at 304-305. For the Dochniak Petition, EPA must respond by June 3, 2008. EPA is allowing public comment until Monday, May 12, 2008. 6
D. EPA Uses Generally Accepted Scie ncific Principles To Assess Data EPA’s notice of the Latex A dhesive Petition states that EPA uses the “Assessment Factors Document” to evaluate data quality. These Factors include:

“ Soundness - The extent to which the scientific and technical procedures, measures, methods or models employed to generate the information are reasonable for, and consistent w ith, the intended application. Applicability and Utility - The extent to which the information is relevant for the Agency’s intended use. Clarity and Completeness - The degree of clarity and completeness with which the data, assumptions, methods, quality a ssurance, sponsoring organizations and analyses employed to generate the information are documented. Uncertainty and Variability - The extent to which the variability and uncertainty (quantitative and qualitative) in the information or in the procedures, measures, methods or models are ev aluated and characterized. Evaluation and Review - The extent of independent verification, validation and peer review of the information or of the procedures, measures, methods or models. ” 7

(continued...) 6 Dochinak Petition Fed. Reg. Notice, 73 Fed. Reg. at 22,369.

7 EPA Science Policy Council, A Summary of General Assessment Factors for Evaluating the Quality of Scientific and Technical Information at 4 (EPA 100/B-03/001, June 2003) (“Assessment Factors Document”) (available at <http://www.epa.gov/OSA/spc/ pdfs/assess2.pdf>) was prepared under the auspices of the EPA ScienceDocket ID Number EPA–HQ–OPPT–2008–0273 May 12, 2008 Page 7

________________________ (continued...) The Assessment Factors Document “complements the Guidelines for Ensuring and Maximizing the Quality, Objectivity, Utility, and Integrity of Information Disseminated by the Environmental Protection Agency.” 8 The EPA Information Quality Guidelines “involves a ‘weight-of-evidence’ approach that considers all relevant informa tion and its quality, consistent with the level of effort and complexity of deta il appropriate to a part icular risk assessment.” 9 EPA relies upon “the best available science and supporting studies conducted in accordance with sound and objective scientific pract ices, including, when available, peer reviewed science and supporting studies,” “data collected by accepted me thods or best available methods, and use of comprehensive, informative information. 10
Scientific causation “can be answered onl y through ... formulating a question that can be answered, designing a study that can answer it, collecting objectivel y verifiable evidence that will address the question, and drawing only those conclusions supported by the evidence.” 11

Policy Council (SPC) to describe the assessment factors and considerations generally used by the Agency to evaluate the quality and relevance of scientific and technical information. Id . at iv.

8 Id . at 1.

9 Guidelines for Ensuring and Maximizing the Quality , Objectivity, Utility, and In tegrity of Information Disseminated by the Environmental Protection Agency at 21 (EPA/260/R-02-008), available at < http://www.epa.gov/QUALITY/informationguidelin es/documents/EPA_Inf oQualityGuidelines.pdf .>.

10 Id . at 22.

11 Brief of Amicus Curiae The New England Journal of Medicine and Marcia Angell, M.D., In Support of Neither Petitioners Nor Respondents at 5, in General Electric Co. v. Joiner , 522 U.S. 136, 118 S. Ct. 512 (1997).Docket ID Number EPA–HQ–OPPT–2008–0273 May 12, 2008 Page 8
However, if the theory passes the test, it “is not confirmed, but merely corroborated.” 12
Causation is determined after an evaluation of the weight of all the scientific evidence in light of: (1) the temporal relationship; 13 (2) consistency of the effect across different studies; 14 (3) the magnitude of the theoretic inci dence of disease in an expos ed population compared to an unexposed or less exposed population (called re lative risk) found in the studies (i.e. , preferably there is a relative risk ratio 15 of greater than 2.0); 16 (4) whether there is a biological gradient between the level of exposure and the magnitude of the effect (that is, does higher exposure

12 National Academy of Sciences proceeding on scien tific evidence workshop: Science, technology, and law program at 12 (September 2000), at http://www7.nationalacademies.org/stl/Scientific_Evidence_PDF.pdf (“NAS Scientific Evidence Workshop”).

13 The adverse health effect has to occur within a biologically reasonable time after initial exposure. Because some adverse health effects are believed to become manifest only after a latenc y period, the determination of temporal effect is no t always straightforward.

14 The strongest association occurs when the same effect in the same organ with the same biological mechanism is observed in several independent studies of a similar exposure in different populations. The association may be strong if it consistently occurs in di fferent subgroups in the same study. Bias and confounding factors need to be taken into account in reviewing multiple studies.

15 The relative risk is the ratio of the risk of disease or death among the exposed population to the risk in the unexposed population.

16 A statistically significant relative risk of 2.0 means that the more exposed population had twice the rate of disease than expected from an exam ination of a population that was not exposed or significantly less exposed. Thus, in those situations where, based on the weight of the evidence, the exposure cause d an increased relative risk of 2.0, any one individual in the exposed population would have a 50% probability of having their disease caused by the exposure. J. Rosenbaum, Lessons from Litigation over Silicone Br east Implants: A Call for Activism By Scientists , Vol. 276, SCIENCE, No. 5318, Issue 6, p. 1524 (June 6, 1997), at http://www.sciencemag.org/content/vol276/issue5318/

. According to US EPA, “when a relative risk is less than 2, if confounders [i.e. , other potential causes of the disease being studied]... are having an effect on the obse rved risk increases, it could be enough to account for the increased risk.” US EPA, Health Assessment Document for Diesel Engine Exhaust at 7-138 (EPA/600/8-90/057F, May 2002), at http://cfpub.epa.gov/ncea/cfm/ recordisplay.cfm?deid=29060

.Docket ID Number EPA–HQ–OPPT–2008–0273 May 12, 2008 Page 9
result in a higher incidence of disease); 17 (5) the specificity of the association; 18 (6) the biological plausibility that the exposure could cause the effect; 19 and (7) coherence. 20 Thus, a statistical association in one or even a few studies is typically not sufficient to determine that an exposure caused cancer, unless the cancer is rare and the risk ratio is very large. Thus, there are well established data evaluation rules that EPA must follow. E. The Requested Relief – Banning the Use or Impact of “Latex Adhesives” In this case, the Petitioners request that EPA totally ban the use or sale in interstate commerce of “latex adhesives”. Even if there were a risk, which, in any event, is not supported by the scientific evidence, there are many less burdensome approaches than a ban.

17 Generally, the risk ratio should increase with increasing exposure or dose.

18 For most chemicals, exposure resu lts in a specific type of disease or adverse health outcome. It is generally considered less biologically plausible to hypoth esize a substance that would cause an increase in all diseases or all cancers.

19 Biological plausibility is the factor that is both conceptually simple to understand, yet difficult to apply. The mechanism for many diseases is not yet fully understood. Generally, toxicologists evaluate data from animal studies, the toxicokinetics of the substance (i.e., how the chemical moves through the body and interacts with cells), the structure-activity relationship compared to other known carcinogens, and the data from short-term studies of the agent’s influence on biological steps known or believed to occur.

20 Evaluating coherence involves comparing the assume d cause-and-effect relationship with what is known about the history and biology of the disease, i.e., the entire body of knowledge about the agent. Some authors do not include coherence as a se parate factor. The A.B. Hill. criteria have long been recognized as the key criteria to assess causality.Docket ID Number EPA–HQ–OPPT–2008–0273 May 12, 2008 Page 10



### II. THE WEIGHT OF SC IENTIFIC OPINION FAVORS A FINDING THAT EXPOSURE TO NATURAL LAT EX RUBBER DOES NOT CAUSE AUTISM The Dochniak Petition alleges that: (a) natural rubber latex "has seen a dramatic increase in usage over the last 30-years;" (b) this timing coincides with an increase in the diagnoses of autism; and (c) natural rubber la tex causes allergic react ions in the general population. The petition also make s a number of unsupportable stat ements such as "an immune response associated with Hev-b proteins ma y induce IgE-secreting lymphocytes to form antibodies that target dissimilar exogenous/e ndogenous proteins thr ough the cross-react mechanisms." Autism spectrum disorders Exog enous protein insult ar ticle at 545-46. The risk assessment process generally requ ires: (a) a hazard identification (i.e., the substance at some plausible exposure level is capable of causing the adverse health impact), (b) evidence of exposure; (c) a dose-response (i.e ., evidence that there is scientific correlation between exposure and the adverse response) ; and (4) the risk characterization (i.e ., the quantitative risk from the likely exposure). None of these elements have been met. The allegations in the Dochniak Peti tion are just that -- unsupported and unsupportable allegations. Given the short period of time available to review the material, the RMA provides the following prelimin ary list of fundamental problems with the allegations. This list is not complete. 1. The paper attached to the Dochniak Peti tion is not a peer reviewed journal ("TSCA Petition Paper").Docket ID Number EPA–HQ–OPPT–2008–0273 May 12, 2008 Page 11
The TSCA Petition Paper is published in "Medical Hypotheses." The editors of Medical Hypothesis candidly state th at this publication takes a delib erately different approach to review. Most contemporary practice tends to discriminate against radical ideas that conflict with current theory and practice. “ Medical Hypotheses will publish radical ideas , so long as they are coherent and clearly expressed. Furthermore, traditional peer review can oblige authors to distort their true views to satisfy referees, and so diminish authorial responsibility and accountability. In Medical Hypotheses, the authors' responsibility for the integrity, precision and accuracy of their work is paramount.” 21 (bold face and red highlighting added). According to the author's web site, the "costs of publication of the Med. Hypotheses article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C.Section 1734 solely to indicate this fact.)" 22 In short, this is a radical theory propounded by the author. By definition, publication in Medical Hypothesis means that th is “radical” allegation in the TSCA Petition Paper is not generally accepted and does not follow scientifica lly sound, reproducible methodology. The TSCA Petition Paper does not even attempt to statistically correlate increased use (however defined) with increases in autism. In the field of Autism diagnosis, there has been considerable increase in physicians’ ability to detect autism in the la st 30 years. But even if there

21 Available at < http://www.elsevier.com/wps/find/journaldescrip tion.cws_home/623059/description#description >).

22 Available at ( http://www.autismdoc.org/page2.html ).Docket ID Number EPA–HQ–OPPT–2008–0273 May 12, 2008 Page 12
is a component of increased risk that is not due to better diag noses, it could be due to other confounding factors, not latex. 2. The TSCA Petition Paper provides no new data, but paraphrases other published articles, newspaper articles and web sites. The TSCA Petition Paper cites no origin al data, and citations to newspaper articles, press releases and ot her nonscientific sources of info rmation are not the type of “scientific evidence” that EPA’s Assessment Factors Document and Information Quality Guidelines permit EPA to be rely upon in promulgating a TSCA rule. 3. No peer reviewed scientific articles s upport a relationship between exposure to natural latex rubber and autism.

The assertions made in the Dochniak Pe tition are not supported by any scientific evidence or generally accepted scientific methodology. A search of Medline yielded no peer reviewed scientific studies that found a correlat ion between exposure to natural latex proteins and autism. Similarly, a search of the National Institute of Environmental Research and EPA web sites found no research inves tigating a hypothetical link betw een exposure to allergenic natural rubber latex proteins and autism. 23 RMA is not aware of any other article (peer reviewed or not) that demonstrates a corr elation between exposure to natura l latex proteins and autism.

23 Obviously, there is research on autism generally and nothing in this comment on the Dochniak Petition suggests otherwise. However, no researcher, as far as RMA can determine, has deemed testing this allegation worth the expenditure of limited research funds.Docket ID Number EPA–HQ–OPPT–2008–0273 May 12, 2008 Page 13
The Food and Drug Administration, 24 the Consumer Product Safety Commission, 25 the National Institute of Occupational Safety and Health, 26 the American Conference of Governmental and Indus trial Hygenists (“ACGIH”) (2008), 27 and the Occupational Safety and Health Administration 28 have investigated allergic reactions to natural rubber latex proteins, primarily from dipped rubb er products (discussed below). None of these agencies (although focused on allergic reactions from exposure to natura l rubber latex) found a link to autism. Natural rubber latex has been utilized for over a hundred years without any observation of a link (even among the rubber farms and latex processor workers who have significantly higher levels of exposure).

24 FDA, Natural Rubber-Containing Medical Devices; User Labeling, 62 Fed. Reg. 51,021 (September 30, 1997). This rule covers medical adhesives that are in contact with humans. Id. at 51,024. On 12/20/2007, Michael J. Dochniak (the author of th e Dochniak TSCA Petition that is the subject of this comment) also filled a petition (2007P-0486) requesting the issuance of a regulation for Hevea Basiliensis naturalrubber-latex, used in the manufacture of infant products (available at < http://www.fda.gov/ohrms/docke ts/CITPETS/07citpetlist.htm >. It is pending.

25 Letter from Todd Stevenson, Secretary of CPSC to Ms. Debra Adkins, Petitioner, re: Denying the petition requesting the CPSC to declare natu ral latex rubber a strong sensitizer at 2 (June 4, 2004), in part because exposure to consumer products containing natural latex rubber (including adhesives) resulted in few documented cases of allergic reactions and most were from me dical devices within the jurisdiction of the FDA.

26 NIOSH, Alert, Preventing Allergic Reactions to Natural Rubbe r Latex in the Workplace (June 1997, DHHS (NIOSH) Publication No. 97-135), available at < http://www.cdc.gov/niosh/latexalt.html >.

27 The ACGIH threshold limit value ("TLV") for natural latex is 0.0001 mg/m 3 , as Inhalable allergenic proteins. ACGIH, Natural Rubber Latex: TLV® Chemi cal Substances 7th Edition Documentation (Publication #7DOC-720)(2008), available at < http://www.acgih.org/store /ProductDetail.cfm?id=1706 >). This review did not find any relationship between autism and natural latex rubber.

28 OSHA, Technical Information Bulletin – Potential for Allergy to Natural Rubber Latex Gloves and other Natural Rubber Products (April 12, 19 99). See OSHA, Hosp ital eTool - HealthCare Wide Hazards Module Latex Allergy, available at <http://www.osha.gov/S LTC/etools/hospital/hazards/latex/latex.html >.Docket ID Number EPA–HQ–OPPT–2008–0273 May 12, 2008 Page 14

4. The TSCA Petition Paper does not define, quantify or correlate exposure to allergenic natural rubber latex proteins and autism (even though the Dochniak Petition repeatedly claims some relationshi p between allergenic natural rubber latex proteins and the increase in the diagnosis of autism) Exposure is essential both to identifying a hazard, as well as calculating the risk. Here, there simply is no effort to define or ca lculate exposure and correl ate that exposure to the rates of autism. Even some of the allegations concerning exposure to natural latex rubber are incorrect, imprecise or unavailable. First, contrary to the statements in the Petition, use of natural rubber latex in the US has not dramatically increased. 29 Second, the Dochniak Petition does not provi de any evidence that natural rubber latex allergens are transported from natural latex rubber adhesives in to humans and, if so, at what levels. Exposure requires eviden ce that there is a significant re lease of latex allergens from adhesives and that these a llergens enter the human body at significant level. Third, the TSCA Petition Paper fails to dist inguish between natural latex proteins from dry rubber and dipped rubber, which are th e two basic types of ma terials used to produce NRL products. The different processes involved in producing dry rubber or dipped latex rubber

29 According to the Rubber Manufact urers Association, Factbook 2006, US Tire Shipment Activity Report For Statistical Year 2005, the use of total US rubber consumption has increased 18.6% from 1970 to 2003 (an average of 0.56% per year). Si milarly, FAO indicated that use of natural rubber in US would decrease from 2000 to 2010. The Food and Agricultural Organization of the United Nations, FAO Corporate Document Repository, available at http://www.fao.org/docrep/006/y5143e/y5143e1d.htm >). Much of these long te rm increases are due to increases in population and, therefore, would not necessa rily result in an increase in the average exposure to individuals.Docket ID Number EPA–HQ–OPPT–2008–0273 May 12, 2008 Page 15
products result in dry rubber products having very low levels of bioa vailable NRL proteins compared to most dipped latex products. Products made from liquid latex are usua lly very thin, pliant, and elastic. Examples of these types of products include gl oves, condoms, and balloons. These products are made by dipping glass or porcelain molds into th e liquid latex and allowi ng the latex to dry on the mold. The dipping process is repeated a de fined number of times to achieve the desired thickness (Subramaniam 1995). It has been demonstrated that dipped latex products contain extractable NRL allergens that may become bioavailable under cert ain conditions (Alenius et al. 1994; Yip et al. 1994; Yunginger et al. 1994; Lu et al. 1995; Yunginger 1995). Products made from dry rubber are thicker, less pliant, and sometimes very rigid. Examples of dry rubber products include tires, hoses, belts, ^ sports equipment, balls, and some baby pacifiers and bottle nipples. Dry rubber pro ducts are produced via a process that includes extremes of heat and pH, extensive processing, and the addition of a large proportion of fillers (Subramaniam 1995). NRL proteins in dry rubbe r products are largely denatured, diluted, and immobilized to a far greater extent than in products fo rmed from liquid latex (Yip et al. 1994; Yunginger et al. 1994; Yunginger 1995). In fact, most dry rubber products that have been tested have had no detectable leve ls of latex allergens (Yip et al. 1994; Yunginger et al. 1994; Yunginger 1995; Thomsen and Burke 2000) and di d NOT elicit strong allergic reactions in sensitized patients when challenged with a skin pr ick test with an extract from the various dry rubber products and dry rubber com pound mixtures (Yip et al. 1994) ( see Table 1 below).Docket ID Number EPA–HQ–OPPT–2008–0273 May 12, 2008 Page 16

Table 1: Extractable Latex A llergens from Rubber Products RUBBER PRODUCT ALLERGENIC RESPONSE (skin-prick test) ALLERGEN (AU/ml) SMR CV/vulcanisate a 0 NA SMR L/vulcanisate a 0 NA SMR 10/vulcanisate a 0 NA SMR 20/vulcanisate a 0 NA Hot Water Bottle 0 NA Divers Flippers 0 NA Latex Glove (dipped) 100 NA Baby pacifier NA <5 Baby bottle nipples NA <5 Intravenous tubing NA <5 Rubber ballons (dipped) NA 4,7000 a. Yip et al. 1994 b. Yunginger et al. 1994 NA: Not assessed SMR: Standardized Malaysian Rubber SMR CV: Standardized Malaysian R ubber – viscosity stabilized rubber SMR L: Standardized Malaysia n Rubber – light-colored rubber SMR 10 and 20: Standardized Malaysian Rubber th at is graded based on the amount of dirt in the rubber sample. As noted below, the difference in the le vel of potential exposure to bioavailable NRL between dipped latex products in the hea lth-care setting and dry rubber products in consumer products is magnified even more by the differences in the exposure scenarios. Precisely because a small perc entage of individuals in the population are allergic to natural latex rubber, there is less likelihood that significant exposure can occur from natural latex rubber adhesives. Either the adhesive is not in contact with the public or the adhesive contacts the skin and contact dermatitis alerts th e person wearing the adhesi ve of the allergy. As a result, there is unlikely to be long term exposure to natural latex rubber in adhesives. Finally,Docket ID Number EPA–HQ–OPPT–2008–0273 May 12, 2008 Page 17
if there was exposure to adhesi ves, it would primarily be th rough medical bandages that use adhesives and RMA believes that FDA, not EPA, would have jurisdiction. In summary, it is not clear there has been a significant increa se in the use of natural latex rubber in adhesives. Although there was an increase in the use of latex surgical gloves (a dipped rubber product) to protect the health of health car e workers, this does not mean that there was a similar increase in the use of dry rubber products (which have not had a dramatic increase in use). The TSCA Petition Paper fails to acknowledge that there has been a dramatic decrease in the use of latex gloves. 5. More generally, the allegation in the Dochniak Petition is that all allergens may be related to autism, not just allergenic natural latex rubber proteins, therefore, any evaluation would need to examine (equally) all allergenic substances (natural and manmade), rather than focus on just natural latex rubber. The allegation presented in the TSCA Petition Paper is that there is a link between any allergic reaction and autism. Many subs tances including ragweed and other prevalent allergens stimulate the same type of allergic reactions as allergen ic natural latex rubber proteins. Ignoring the lack of evidence for this allegation, the implication is that every allergic reaction would impact autism. Additionally, the fact that the Dochniak Petition supports multiple allergens undercuts the allegations in the Petiti on that natural latex rubb er in adhesives cause autism. 6. The Dochniak Petition does not demonstrate a dose-response between natural latex rubber allergens and autismDocket ID Number EPA–HQ–OPPT–2008–0273 May 12, 2008 Page 18

It is essential to a determination ofan unreasonable risk to develop a doseresponse. No such demonstration is ev en attempted in the Dochniak Petition. 7. The Dochniak Petition fails to address th e numerous confounding factors that would need to be assessed in determining whet her exposure to natural latex rubber allergens causes autism. 8. In many cases, the citations provided in the TSCA Petition do not support the corresponding allegations in the text. For example, the paper states that "In humans, repeated exposure to the Hev-b proteins during pregnancy may aff ect the genetic code of immune cells possibly making the fetus more susceptible to ASD [7]" at 546. Reference 7, however, is a newspa per article about a study that found "Expectant mothers suffering from asthma, allergies or a type of skin disease have a higher risk of giving birth to an autistic child" and "there was no statistical link between autism in children and 44 auto-immune diseases in moth ers, including rheumatoid arthritis, lupus and multiple sclerosis." The article states that th e researchers "speculated that there may be a common underlying genetic cau se to such ailments as asthma a nd autism." Nothing in this news article refers to repeated exposure to Hev-b proteins. Also, the TSCA Petition Paper states: In genetic research, studies conti nue to find mutations associated with immunity that may affect the incidence of allergy induced autism. Several candidate gene loci are described below: Chromosome-1 [1q23, Fc fragment of IgE] [30]; Chromosome-11 [11q12-q13, IgE responsiveness][31]; and Chromosome-19 [19p13.3, CD23] [32]. Reference 31 (which has a slightly different title) does not discuss na tural rubber, latex or autism. Rather the article cited in Reference 31 describes "the chromoso mal localization of theDocket ID Number EPA–HQ–OPPT–2008–0273 May 12, 2008 Page 19
gene for squamous cell carcinoma-associated reac tive antigen for cytotoxic T cells (SART-1)." Likewise, Reference 32 is a press release entitle d: “Key molecular signaling switch involved in allergic disease identification.” 30 Finally, Reference 30 is an abstra ct of a poster of a study of the genetic component or nature of autism. In f act, the study connected 21 Finnish autism families by genealogical links extending to 17th century. It does not me ntion natural rubber or latex. In other cases, the text of the paper cites a series of statements and implies that they lead to a conclusion that there is a connection between na tural latex protein exposure and autism. For example, the paper states that homologous enolases from yeasts, molds, and fungi are known to cross-react with Hev-b 9 [22]. Studies indicate that elevated levels of Candida Albicans in some autistic individuals may exacerbate many behavior and health problems, especially those with lateonset autism [23]. A Hev-b 9 indu ced cross-react immune response to exogenous enolases may further affect allergy induced autism. Reference 23, however, does not even mention He v-b 9. As the quote indicates, the web site in Reference 23 simply states that exposure to Candida Albicans in some people may aggravate symptoms. In fact, the web site states that "treat ment for candida albicans infrequently results in a cure for autism." As writ ten, the paper is misleading.

30 Available at < http://hmg.oxfordjournals.org/cgi/content/full/11/18/2143 >). < www.sciencedaily.com/releases/2006/10/061029174930.htm/ > (October 30, 2006).Docket ID Number EPA–HQ–OPPT–2008–0273 May 12, 2008 Page 20



### III. THERE IS NO EVIDENCE TO DEMONSTRATE A CAUSAL LINK BETWEEN EXPOSURE TO NATURAL LATEX RUBBER ADHESIVES AND AUTISM EPA guidance requires sound, applicable, and complete evidence that follows generally accepted scientific principles. The evidence on the Petition fails to meet any of these criteria. In fact, there is no scie ntific evidence of an unreasonable risk of autism from exposure to natural latex rubber allergens from adhesives. 31 The relief being sought in the Dochniak Petition on natural rubber latex adhesive products does not meet TSCA’s “least burdensome” requirement. For example, in the case of latex used in health care (e .g., rubber gloves), the FDA simply required labeling latex containing items to warn health care workers of the potential for an allergic reaction. RMA appreciates the opportunity to comme nt and urges EPA to consider these comments. Please feel free to contact us if we can provide you with any further information. Yours truly,

Tracey J. Norberg Senior Vice President Rubber Manufacturers Association

31 Latex rubber may even reduce the symptoms of autism, according to one member of the Autistic Society who has successfully used "trance suits," i.e., inflatable natural latex rubber suits. Autistic Society Internet Page, available at < www.autisticsociety.org/Forums/vie wtopic/t=1920/view=previous.html >.Docket ID Number EPA–HQ–OPPT–2008–0273 May 12, 2008 Page 21
cc: Colby Linter, Regulator y Coordinator, Environmental Assistance Division (7408M), Office of Pollution Prevention and Toxics, Environmental Protection Agency Gerry Brown, Chemical Control Division ( 7405M),Office of Pollution Prevention and Toxics, Environmental Protection AgencyDocket ID Number EPA–HQ–OPPT–2008–0273 May 12, 2008 Page 22

REFERENCES Alenius et al. 1994: Alenius, H., S. Makinen-Kiljunen, K. Turjanmaa, T. Palosuo, and T. Reunala. 1994. Allergen and protein conten t of latex gloves. Ann. Allergy 73(4):315–320.
Lu et al. 1995: Lu, L.J., V.P. Kurup, J.N. Fi nk, and K.J. Kelly. 1995. Comparison of latex antigens from surgical gloves, ammoniated a nd nonammoniated latex: Effect of ammonia treatment on natural rubber la tex proteins. J. Laboratory Clin. Med. 126(ISS 2):161–168. Subramaniam, A. 1995. The chemistry of natural rubber latex. Latex Allergy 15(1):1–20. Yip et al. 1994: Yip, E., K. Turjanmaa, K.P. Ng , and K.L. Mok. 1994. Allergic responses and levels of extractable proteins in NR latex glov es and dry rubber products . J. Nat. Rubb. Res. 9(2):79–86. Yunginger, J.W. 1995. Variance s in antigenicity of latex Products. Immunology and Allergy Clinics of North America 15(1):61–70. Yunginger, J.W., R.T. Jones, A.F. Fransway, J. M. Kelso, M.A. Warner, and L.W. Hunt. 1994. Extractable latex allergens and pr oteins in disposable medical gl oves and other rubber products. J. Allergy Clin. Immun. 93(5):836–842.