Document Yr8vEbyDmYOkLNwygx7RJznRN

FILE NAME: Doubt Science (DBTS) DATE: 2006 DOC#: DBTS008 DOCUMENT DESCRIPTION: Editorial from Environmental Health - Selected Science: An Industry Campaign to Undermine an OSHA Hexavalent Chromium Standard Environm ental Health: A Global Access Science Source q BiotVled Central Com mentary Open Access Selected science: an industry campaign to undermine an O S H A hexavalent chromium standard David M ichaels*1, Celeste Monforton1 and Peter Lurie1'2 Address: 'The Project on Scientific Knowledge and Public Policy, Department o f Environmental and Occupational Health, The George Washington University School o f Public Health and Health Services, 2100 M Street NW, Suite 203, Washington, DC, 20037, USA and 2Public Citizen Health Research Group, 1600 20th Street NW, Washington, DC, 20009, USA Email: David Michaels* - eohdmm@gwumc.edu; Celeste Monforton - eohcnm@gwumc.edu; Peter Lurie - plurie@citizen.org * Corresponding author Published: 23 February 2006 Received: 10 November 2005 Environmental Health: A Global Access Science Source 2006, 5:5 5 doi: 10.1186/I476-069X-5- Accepted. 23 February 2006 This article is available from: http^/www.ehjournal.net/content/5/1/5 2006 Michaels et al; licensee BioMed Central Ltd. This is an O pen Access article distributed under the terms of the Creative Comm ons Attribution License fhttp://creativecommons.or;/licenses/bv/2.01. which permits unrestricted use, distribution, and reproduction in any medium, provided the original w ork is properly cited. A b s t r a c t___________________________________________ _____________________________ While exposure to hexavalent chromium (Cr(VI)) has been associated with increased lung cancer risk for m ore than 50 years, the chemical is not currently regulated by the U.S. Occupational Safety and Health Administration (OSHA) on the basis of its carcinogenicity. The agency was petitioned in i 993 and sued in 19 9 7 and 2002 to lower the workplace Cr(VI) exposure limit, resulting in a cou rt order to issue a final standard by February 2006. Faced with the threat of stronger regulation, the chromium industry initiated an effort to challenge the scientific evidence supporting a m ore protective standard, This effort included the use of "product defense" consultants to conduct post hoc analyses of a publicly-funded study to challenge results viewed unfavorably by the industry. The industry also commissioned a study of the mortality experience of workers at four lowexposure chromium plants, but did not make the results available to OSHA in a timely manner, despite multiple agency requests for precisely these sorts of data. The commissioned study found a statistically significant elevation in lung cancer risk among Cr(VI)-exposed workers at levels far below the current standard. This finding changed when the multi-plant coh ort was divided into two statistically underpowered components and then published separately. The findings of the first paper published have been used by the chromium industry to attempt to slow OSHA's standard setting process. The second paper was withheld from OSHA until it was accepted for publication in a scientific journal, after the rulemaking record had dosed. Studies funded by private sponsors that seek to influence public regulatory proceedings should be subject to the same access and reporting provisions as those applied to publicly funded science. Parties in regulatory proceedings should be required to disclose whether the studies w ere performed by researchers who had the right to present their findings without the sponsor's consent o r influence, and to certify that all relevant data have been submitted to the public record, whether published o r not. Background In recent years, efforts by major corporations to deflect unwanted scientific findings have been reported increasingly in the lay and biomedical literature. The tobacco P a ge 1 of 8 (page number not for citation purposes) Environmental Health: A Global Access Science Source 2 0 0 6 ,5 :5 http://www.ehjournal.net/content/5/1/5 industry, for example, used the attorney-client privilege to shelter scientific studies from disclosure [1-3]; it also funded apparently independent organizations to provide a patina o f credibility for its work [1,4]. Pharmaceutical manufacturers have withheld unfavorable clinical trial results [5,6] and have disparaged research that produced unwelcome findings [7,8]. We report a case in the less-scrutinized field of occupa tional health in which all these elements were combined in a coordinated strategy to challenge the Occupational Safety and Health Administration's (OSHA) action to reduce workers' exposures to the lung carcinogen hexava lent chromium (Cr(VI)). Cr(VI) is not a newly-identified hazard; the increased risk o f lung cancer has been documented in Cr(VI)-exposed workers for more than 50 years [9,10]. Thomas F. Mancuso and Wilhelm C. Hueper, for example, studied the mortality experience o f chromium-exposed workers employed between 1931 and 1937 at a Painesville, Ohio facility. Results o f their study were published in 1951 [10,11], with updates on the cohorts published by Dr. Mancuso in 1975 [12] and again in 1997 [13], consist ently finding an excess risk of lung cancer among exposed workers. Cr(VI) has been classified as a human carcinogen by the National Toxicology Program [14] and the Interna tional Agency for Research on Cancer [15], It is used in chrome plating and in the production o f metal alloys and pigments. OSHA estimates that approximately 380,000 U.S. workers are currently exposed to Cr(VI) [16]. At present, OSHA does not regulate Cr(VI) on the basis of its carcinogenicity. The agency's current Permissible Expo sure Limit (PEL) o f 52 ug/m3was originally recommended in 1943 by the American National Standards Institute as a level adequate to prevent nasal perforations in chromiumexposed workers [17]. This 52 ug/m3limit was adopted by OSHA in 1971 when the agency was created, without any formal review. In 1976, OSHA announced plans to lower the Cr(VI) standard [18] and in 1994, the OSHA adminis trator acknowledged that "there is clear evidence that exposure...at the current PEL...can result in an excess risk o f lung cancer" [19]. However, until recently, no change was officially proposed and the 5 2 ug/m3 PEL remains in effect today. In 1993, Public Citizen and the Oil, Chemical and Atomic Workers International Union (OCAW) (now part o f the United Steelworkers) petitioned OSHA to reduce its PEL from the current level of 52 ug/m3 to 0.25 ug/m3, meas ured as an 8-hour time-weighted average. Two lawsuits ensued, challenging OSHA's "unreasonable delay" in promulgating a stronger standard. Although the chro mium industry, through its trade association the Chrome Coalition, had intervened in the lawsuits on OSHA's behalf opposing a change in the PEL, on April 2 ,2 0 0 3 , the U.S. Court o f Appeals for the Third Circuit ordered the agency to issue a final rule reducing occupational expo sure to Cr(VI) by January 18, 2006 [20], later extended to February 28, 2006. In the words o f Judge Edward Becker, OSHA's decade-long delay in issuing a Cr(VI) standard "exceeded the bounds of reasonableness" [21]. The industry strategy to forestall O S H A rulemaking Long before the court ruling, however, the chromium industry had initiated an effort to challenge the scientific evidence supporting any stronger OSHA standard, engag ing the services o f ChemRisk and Exponent, Inc., two con sulting firms that specialize in "litigation support" and "product defense" [22,23], One industry document noted that "this route [hiring the consultants] is expensive and success is not guaranteed, [but] the longer we wait the more difficult the task becomes." [See additional file 1: Filel to view this document.] In a meeting with chromium industry representatives in 1996, ChemRisk scientists outlined a strategy that included obtaining and analyzing the raw data from a not-yet-published study of Cr(VI) exposure funded by the Environmental Protection Agency (EPA) in order "to fore stall the [OSHA] rulemaking." [See additional file 2: File2 to view this document.] Simultaneously, the industry commissioned new publications that questioned the health effects o f low levels o f exposure to Cr(VI) [24-26], a central issue in any OSHA regulatory initiative. The industry paid for services provided by ChemRisk and Exponent, Inc. through its trade association's attorneys. This arrangement was selected to "...preserve the confi dentiality o f information, opinion, and data to the extent provided for under the attorney-client privilege and attor ney work product privilege." [See additional file 3: File3to view this document], ensuring that material developed through the process could be sequestered from public view. [See additional file 4: File4 to view meeting sum mary and plan to preserve attorney-client privilege.] The industry also contracted with a third consulting firm, ENVIRON [27], to study workers who had only been employed in facilities that were either designed with or converted to production processes that resulted in lower levels o f Cr(VI) exposure. ENVIRON was hired through a contract with the Industrial Health Foundation (IHF), a descendant of the Air Hygiene Foundation, an organiza tion founded in 1935 in the wake o f the 1930's Gauley Bridge occupational silicosis tragedy to provide employers with confidential assessments o f industrial hazards [28]. The study protocol entailed combining workers from four plants using newer, lower-exposure processes - two in the U.S. (Castle Hayne, NC, and Corpus Chnsti, TX) and two P age 2 of 8 (page number not for citation purposes) Environmental Health: A Global Access Science Source 20 06 , 6:5 http://www.ehjournal.net/content/5/1/5 in Germany - into a single cohort. ENVIRON's proposal noted that "the relatively small study sizes and short fol low-up periods resulted in a limited ability o f [previous] studies to clarify the relationship between modern [lowlevel] occupational chromate exposures and cancer in general, and respiratory cancers in particular." According to the proposal, creating a single cohort with workers from multiple plants was crucial "to improve statistical power and the inferential value o f the results" [29], Following a three-month comment period, OSHA held 11 days o f public hearings [38], at which OSHA reiterated its request for more data and industry repeatedly criticized OSHA for relying on data from high-exposure cohorts [39-44], In reviewing the hearing transcript, we found no mention by industry representatives or anyone else o f any imminent new epidemiological evidence. The public was given until April 20, 2005, to submit additional data and post-hearing comments. In August 2000, the EPA study was published. It is the largest, most comprehensive study ever conducted on the effects o f workplace Cr(VI) exposure. The study examined a cohort o f more than 2,300 workers employed at a chro mate production facility in Baltimore, MD, from 1950 to 1974, and followed through 1992. Exposure histories were reconstructed utilizing 70,000 measures o f airborne Cr(VI) concentrations; smoking histories for 93% o f the cohort were also incorporated into the analyses. Using OSHA's standard assumption o f a 45-year working life time, the study reported a significantiy elevated lung can cer risk o f 1.57 among workers whose mean exposure was at levels just above the PEL requested in the Public Citizen-OCAW petition [30], No sooner had the EPA study been published than the industry-sponsored critiques began. Scientists with the product defense firm Exponent, Inc. created and analyzed the mortality experience o f a "simulated cohort" derived by computer from the EPA study's summary data, stand ard deviations and ranges [31]. In another report, the con sultants obtained the raw data from the EPA study through a Freedom o f Information Act request and re-ana lyzed them [32], Each o f these reports challenged the validity o f the EPA study's conclusions and was either entered into the record in litigation or submitted to OSHA by the chromium industry, although not published in the peer-reviewed literature. After extensive analysis, most o f the issues raised in these critiques were rejected by OSHA {33]. OS H A publishes its proposed rule On October 4, 2004, OSHA published its court-mandated proposed rule for Cr(VI), including a PEL o f 1 ug/m3 [34], The agency issued a general request for additional scien tific evidence, along with a specific appeal for epidemio logical data about the aforementioned cohort in Castle Hayne, where exposure levels were more representative o f the concentrations o f airborne Cr(Vl) found in work places today [35], A mortality study o f this group had been published in 1994 [36] and OSHA asked directly, "Are there updated analyses available for [this cohort]?" In addition, OSHA asked, "Are there other cohorts availa ble to look at low exposures?" [37], Selected science Just weeks before the close o f the comment period, a study reporting on the mortality experience of workers employed at the Castie Hayne and Corpus Christi facili ties appeared in the Journal o f Occupational and Environ mental Medicine (JOEM) [45], The article had been submitted to JOEM in July 2004 and was accepted for publication that October [46], the same month OSHA proposed its mle and specifically asked for information about the Castle Hayne or other cohorts. The analysis has little statistical power (only three lung cancer deaths) and suffers from short follow-up (fewer than half o f the work ers in the study were followed for twenty years or more, the minimum length o f time needed to begin to detect occupational cancer) [47], Even though they collected data on Cr(VI) exposure, none is presented in the paper and the small sample size precludes logistic regression. Nonetheless, the authors offer the "preliminary conclu sion" that "the absence of an elevated lung cancer risk at this time may be a favorable reflection of the post-change [i.e., lower exposure] environment [45]." Three trade associations made reference to the study in their post-hearing comments [48-50], For example, the Specialty Steel Industry o f North America stated it had "recently" learned o f the study: [W]hile we have not had any opportunity to examine this study...[it] contains potentially incredibly significant data which would allow the development o f a dose response relationship based on actual, experienced exposures, as opposed to the modeled exposures upon which OSHA currendy relies to set the PEL. Indisputably, this would be much more relevant and appropriate data upon which to establish a risk-based regulatory limit [48]. The Specialty Steel Industry warned that OS HA's failure to consider these results would be "arbitrary and capricious," a legal term, signaling that failure to address these "new1' findings would be grounds for a legal challenge. The Soci ety o f the Plastics Industry, Inc. (SPI) remarked on the "potentially great significance" [49] o f the new ENVIRON study. P a g e 3 of 8 (page number not for citation purposes) Environmental Health: A Global Access Science Source 2 006, 5:5 http://www.ehjoumal.net/content/5/1/5 Moreover, the comments by these trade associations con firm that they were privy to unpublished details o f the ENVIRON analysis. For example, one wrote: SPI has learned that in the German plants, excess lung cancer mortality was demonstrated only in the highest exposure group, using chromium exposure estimates based on urinary chromium results. It is possible that the data obtained from the German facilities demonstrates that no increase in risk at any but the highest exposure lev els to CrVI [49], The industry thus succeeded in inserting this hearsay material into the record without ever providing the actual study data. Intrigued by these developments, we conducted an Inter net search, using the terms "Industrial Health Founda tion" and "Chrome Coalition." To our surprise, we located a notice for a hearing related to the bankruptcy o f IHF. In this proceeding, two chromium industry trade associations asserted that files in the possession o f IHF actually belonged to the industry, because the IHF was, according to the petitioner, simply a "third-party admin istrator o f the trade association." [See additional file 5: File5 to view this document.] Using the Public Access to Court Electronic Records system [51], we obtained docu ments filed with the court, some o f which have been quoted in this manuscript. These materials also led us to parties in the bankruptcy proceedings who provided addi tional documents, including ENVIRON's study protocol and the final report o f the combined study o f the U.S. and German plants. That report, submitted by ENVIRON to IHF in September 2002 but never by the industry to OSHA and never pub lished in its entirety, provides strong support for the inad equacy o f the current standard, and raises questions about whether the proposed OSHA PEL o f 1 ug/m3is adequately protective. The ENVIRON authors found a significantly elevated risk o f lung cancer mortality associated with exposure to Cr(VI) in these newer low-exposure facilities (SMR = 1.66, 95% Cl = 1.08-2.46, using a combination o f German national rates and U.S. state rates for comparison; SMR = 1.37, 95% Cl = 0.89-2.03, using German and U.S. state rates). The investigators developed a series o f job exposure matrices and utilized air monitoring data from the U.S. plants and urine monitoring from the German plants to estimate the exposure history of each worker. In order to convert the urinary measurements (ug/L) into air measurements (ug/m3), we divided by 0.77, the same con version factor used by the industry [52], and divided by 45, to convert cumulative exposures in to m ean annual ones. Logistic regression analyses of the four-plant cohort found increased risk associated with increased cumulative (or lifetime) exposure to Cr(VI). In one analysis, the lung can cer mortality odds ratio among workers with highest annual exposure ( 5.8 ug/m3) was 20.2 (95% Cl = 6.2 65.4), compared to the lowest exposure group (< 1.2 ug/ m3) [53], For the intermediate exposure group (1.2 ug/m3 - < 5.8 ug/m3), the odds ratio was 4.9 (95% Cl = 1.5 16.0), also in comparison to the lowest exposure group [53], Thus, the intermediate group includes exposure at levels only slightly higher than the 1 ug/m5PEL proposed by OSHA in 2004, and showed elevated lung cancer risk at that level. The final unpublished four-plant report reiterated the strength o f the study design: "This study benefited from the multi-site design that provided a reasonably large cohort o f post-change [lower exposure] chromium chem ical workers, along with the corresponding increase in sta tistical power generally lacking in previous studies of post change cohorts" [52]. The published JOEM article, however, reports the mortal ity experience only o f workers at the two U.S. plants stud ied by the ENVIRON researchers. After submitting the results to their sponsors in 2002, the authors evidently separated the German and U.S. results, despite their repeated emphasis in the protocol on the strength o f the combined cohort. Instead of a positive result based on four plants, a negative two-plant study was published. In a response to a letter [54] in the JOEM, the authors stated that the German component o f the study had not been published because it was rejected by a journal to which it had been submitted, and defended the exclusion o f the German data on the ground that different exposure meas urements (air vs. urine) were used [55], This claim is not consistent with the need for large sample size to increase statistical power, as stated in the protocol and the final report. In June 2005, we provided the study protocol [29] and final report o f the four-plant study [52] to OSHA [56]. On October 17, 2005, the ENVIRON researchers submit ted the German component o f the study to OSHA, accom panied by a note saying the paper had been accepted for publication in JOEM [57,58]. In this manuscript, the ENVIRON researchers report that "lung cancer risk was elevated only in the highest exposure group (SMR = 2.09 95% Cl = 1.08-3.65)" [58], The authors conducted another logistic regression analy sis, but in this new version the estimate of relative risk for workers with high exposure is derived by comparing them to workers in the low and interm ediate exposure groups combined. The result o f this change is the disappearance o f the statistically significant increase in lung cancer mor- Page 4 of 8 (page number not for citation purposes) Environmental Health: A Global Access Science Source 2006, 6:5 http://www.ehjoumal.net/content/5/1/5 Table I : Elevated lung cancer mortality risk in intermediate and high exposure groups in original unpublished studyt Mean Exposure to Cr(VI)* O R** 95% Cl Low (< 1.2 ug/m3) Intermediate ( 1 . 2 - <5.8 ug/m3) High (>. 5.8 ug/m3) Ref 4.9 20.2 1 .5 - 16.0 6.2-65.4 lAdapted from Table 17 in: Final report* Collaborative cohort mortality study o f four chromate production facilities, I9 5 8 -I9 9 8 [531. Mean bcposure to C r(V I) derived by dividing cumulative urinary chromium exposure by 0.77 (conversion factor for air concentration), and then dividing by 45 years (O S H A s working life assumption); see text for details. **O d d s Ratio tality risk among the intermediate group that was found in the unpublished final report. Tables 1 and 2, adapted from the unpublished final report [52] and the pre-publi cation manuscript o f the German component o f the study submitted by the authors to OSHA [58], respectively, compare the results o f the two regression analyses. In addition, while the elevation of the lung cancer SMR in the unpublished final report o f the four-plant study was statistically significant, when the cohort was divided into two components, the lung cancer SMR was not statisti cally significant in either the German or U.S. components. Discussion Faced with the threat o f stronger OSHA regulation of workplace exposure o f Cr(VI), a powerful carcinogen, the chromium industry initiated an effort to challenge the sci entific evidence that the agency would likely use to justify a new standard. While criticizing OSHA for relying upon data from high-exposure cohorts, the chromium industry also commissioned a study o f the mortality experience of workers at four plants with lower exposures, the results o f which confirmed the elevated lung cancer risk in such workers. The consultants presented a final report to their chromium industry sponsors in 2002, but industry never provided OSHA a copy o f the full four-plant study. Even when the agency specifically asked for precisely these sorts o f data during its 2 0 0 4 -2 0 0 5 rulemaking proceedings, the chromium industry and the authors remained silent. For publication, industry-funded scientists divided this study into two components and published them sepa rately. The first paper to be published was a statistically underpowered, negative study, the findings o f which are being used by industry to attempt to reduce its regulatory burden. The second paper combined two exposure strata from the final report, resulting in the disappearance o f the stratum o f particular regulatory interest in which a statis tically significant finding was apparent in the unpub lished final report. This allowed the industry trade associations to make the misleading assertion that ele vated lung cancer mortality risk was only seen among workers with the highest exposure histories. OSHA's statute instructs its decision makers to use the "best available evidence" [59] in the rulemaking process. The circumstances regarding these studies raise troubling questions about the ability of government to effectively issue rules protecting public health when studies are con ducted, controlled and selectively published or provided to the rulemaking agency by the regulated industry [8,60], The entry o f the German study into the OSHA record only after it was accepted for publication, months after the reg ulatory docket closed and years after data collection was complete, raises an important question for public health research: when regulatory proceedings are underway, should potentially important data be sequestered until the peer review process is complete? Many U.S. regulatory agencies, including the EPA and the Food and Drug Administration (FDA) rely heavily on unpublished stud ies, submitted by study sponsors, in reaching regulatory decisions. In this case, sponsors withheld data that OSHA requested during an active rulemaking process. Table 2: Lung cancer mortality risk in intermediate group disappears after Germ an component of study published separately Mean Exposure to Cr(V|)* O R** 95% Cl Low and Intermediate (<5.8 ug/m3) Ref High (> 5.8 ug/m3) 6.9 2 . 6 - 18.2 Adapted from B irk T , M undt KA, Dell LD, et al: Lung cancer mortality in the German chromate industry, 1958--1998. / Occub Environ Med fin press) [58], Jr \ Mean Exposure to C r(V I) derived by dividing cumulative urinary chromium exposure by 0.77 (conversion factor for air concentration), and then dividing by 45 years (O S H A 's w orking life assumption); see text for details. **O d d s Ratio Page 5 of 8 (page number not for citation purposes) Environmental Health: A Global Access Science Source 2006, 6:5 http://www.ehjoumal.net/content/5/1/5 It is now widely recognized that pharmaceutical manufac turers have an obligation to report the existence and results o f all clinical trials, although this is often not done satisfactorily [61,62], The higher standards o f practice now being sought in the reporting o f pharmaceutical trial results should also be applied in occupational health and safety research. The editors o f thirteen leading journals will no longer publish articles based on studies done under contracts in which clinical trial investigators did not have the unfettered right to publish the findings, asserting that such restrictions "erode the fabric o f intellectual inquiry that has fostered so much high-quality clinical research" [63]. Parties in regulatory proceedings should be required to disclose whether the studies they submit were performed by researchers who had the right to present or publish their findings without the sponsor's consent or influence [64], Regulatory agencies should weigh the sub mitted information accordingly. Public health is not well served by the unequal treatment o f public and private science [65], Parties submitting sci entific analyses and reports to the record should be required to disclose the true sponsorship o f the study, including the original source o f the sponsor's funding. Parties involved in the rulemaking process should also be required to certify that they have submitted all relevant data to the public record, whether or not those data have undergone peer review. Medical journals are increasingly willing to publish findings even if they have already been made available in another form. Regardless, public health rulemakings should not be based on partial records or limited by scientists' career concerns, particularly when lives hang in the balance. List of Abbreviations Cr(VI) Hexavalent Chromium EPA US Environmental Protection Agency IHF Industrial Health Foundation JOEM Journal o f Occupational and Environmental Medi cine OCAW Oil, Chemical and Atomic Workers International Union OSHA US Occupational Safety and Health Administra tion Competing interests PL is with Public Citizen's Health Research Group, a party in the lawsuit filed against the US Department o f Labor to compel OSHA to issue an occupational hexavalent chro mium standard. DM and CM declare that they have no competing interests. Authors' contributions DM, CM and PL researched and wrote the article. All authors read and approved the final manuscript. Additional material Additional File 1 Chrome Coalition Ad Hoc PEL Committee. Summary o f Chrome Coali tion's meeting with ChemRisk on February 13,1996. Click here for file [http://www.biomedcentral.com/content/suppIementary/1476069X-5-5-Sl.pdf] Additional File 2 Chrome Coalition Meeting Minutes. Meeting minutes describing the Chrome'Coalition's February 13, 1996 meeting with ChemRisk Click here for file [http://www.biomedcentral.com/content/supplementary/1476069X-5-5-S2.pdf] Additional File 3 Agreement between Collier, Shannon, Rill & Scott, PLLC, ChemRisk and the Industrial Health Foundation signed September 10,1996. The agree ment outlines services to be provided by ChemRisk on behalf o f the Chrome Coalition. Click here for file [http://www.biomedcentral.com/content/supplementary/1476069X-5-5-S3.pdf] Additional File 4 Chrome Coalition Meeting Summar)', September 12,2002. Summary o f the Chrome Coalition's meeting on September 12, 2002. Click here for file [http://www.biomedcentral.com/content/supplementary/1476069X-5-5-S4.pdf] Additional File 5 Affidavit o f Dr. foel Barnhart, December 17, 2004, in Re: Industrial Health Foundation, Inc., U.S. Bankruptcy Courtfo r the Western District o f Pennsylvania. The affidavit describes, among other things, the Indus trial Health Foundation's role with respect to the Chrome Coalition. Click here for file [http://www.biomedcentral.com/content/supplementary/1476069X-5-5-S5.pdf] PEL Permissible Exposure Limit SM R Standardized M ortality Ratio g/m3 micrograms per cubic meter o f air Acknowledgements D M and C M are employed by the George Washington University School of Public Health and Health Services as part o f the Project on Scientific Knowl edge and Public Policy (SKAPP). Their salaries, in part, are funded by the Comm on Benefit Litigation Expense Trust, a fund established pursuant to a court order in the Silicone Gel Breast Implant Products Liability litigation. Page 6 of 8 (page number not for citation purposes) Environmental Health: A Global Access Science Source 2006, 6:5 http://www.ehjournal. net/content/5/1 /5 22. ; = = = ~ . ~ - 23. S S S S f u,l!"lms""" W e are grateful to Mr. James W alker of W alker & W ylder Ltd of Rl - rTM*w-- : References "1 T ` " ^ w* MD son documents. JAM A 1995, 274^79-224 B a" d William- s i 3. & r s S 5 K SA:hUwyer " 1995, 274:234-240. Williamson documents. JAMA 4' nantioEna.GAgencAy fo r' t a f t f ! smoke study. Jncet 2000 355:1253 " 259 * seeond-ha" d ^fn*i:eipubiiatinsiiS^^i3EmijjQ ^252_tozf* iaB-/!" c.ngh G-: l^stirriony before the U s S t e C o m m i t Finance, November 18, 2004 Committee on iitepaves/hparinji11 IP^ ^ tnapi/fiaaoM,senate,gpy/ 98' Machfw G r^tu s*F ian cer of the AT ^^' W :9` 101. tries/mediral^m|] 24. top.//wvyw.Bxg8njjnt,cprn/inHi B iPm pV teDdMsc|aenceJ?n RJ: Need for 25. mium. Regul Toxicol Pharmacol 1999, i o i heXaValent chr- ^ S S " : dR'Mund`K'Uebig* *>"<>J, of airborne hexavalent c h r o m i , , ^ 0 ' ! ^ and r*s*t c e s s m e n t 26. RLuisikpAponladl 2R0S0,3,M2u3n:d11t-4K7A-1, 1A6u3stin RP L3inehdiuncdcani cer, m,,ortality. Crump K, Proctor D: Lung cancer J' ? rumP C - 27. production workers I Orr,,h r among chromate In 2004 E N v m o u ' 1 ET on M e d m *. 0:451-457. 28. pany and its predecessor 29. N for both that " 30. 31. n ared ExPonent, Irvine, C A . 2002 33. **' ' pre* l0' T ^T T" i ^ B2 r r ,0n" 1 -- * " d other ^ o m a t e n f c r ^ C m ,': 34. S s s s l r s " " 35. eralR egister59306-S 94I4. O c t o b e r 4 5 Jk 4 roposed RU' e ' 6 9 h d ' 13 nTdT/m y^^ranlndustrialcarcin*e"=p - t I- An l4' n t l a ^ Service: 11 iilS m " 1" " S is " T - I F w b r td K o S : r14 's ^ t i s a a s s as.osha.fov/yr00i/V024A/ni/a[pi P r n ' 94` i?rfj;,sr2i? Jus'TM "7-- 2 I' " " K T S & " F " S TM toa/Zdask . (JSApp. w s i S ; 36. Pastldes H, Austin R, Lemeshow S, Klar J, Mundt KA: A r e t TM TM - tive-cohort study of occupational exposure to hexavafont 37. chromium. AmerJ Ind Med 1994, 25:663-675 a lent 38. 4 5 ? Z l ? , fr Z n ? V Ubli? HeaH" S Socket H0S4A, Exhibit 39. 3 T S a S S S 40. o t H A p 7 b l i ? A e T r T n v PF * " ? lndu5t^ f N h America: V0-447,A/nn/74/H [ ppp[ BtttpdV/dpek,oectst.enHa a05g4pAy/yMgopb\ii! 41. Joan Fessler, Carpenter Technology Corporation- o t u a 8?g; y '5^ ary4,i S 5 S S 42. s p a S ^ ' 43. Marr P, Dominion Colour Corporation: O S H A Rublir W : 44. w^u:..TrwS L/ 'tLo 2p^,//d-ockteotcstoes'hHa.0^5v^/vpn^pI f4yo5r.:9 ,,nfwl,Ydnp,^t nppnj *f ; 65gpDF] 'Q60~ /0d5 ihap://dpckets osha.gov/vffnn [W')47A/00M4/ Page 7 of 8 (page number not for citation purposes) Envi/cnmcntsl H ccltlv A Globe! Access Science S e m e 2006, 5:5 http://www.ehjournal.net/content/5/1/5 45. Luippold R.S, Mundt KA, Dell L D Birk T- Lo w lvi u , c h r o m a e x p o s e and rate ! % 47^8l-385.d employees. J Occup Environ*Med 2005, 46. Spraycar M: Managing Editor, Journal of Occupational and Environmental Medicine: Email to David Michaels, May 16^ 47. international Agency for Research on Cancer: Preamble to IA R C onographs: Studies of cancer in humans. 1998 rhttiv//www. 48 aPoa srtar^hfer/amrionngoebvraile/fsnsiurlbiem^uitmteandshotnmlb] ehalf of Specialty Steel M ?M St|7 i N,rth Am ericasubmitted by counsel, Kathryn McMahon-Lohrer and Kristina Nelson Co llier Shannon Scott, P LLC , April 2 0 ,2 0 0 5 Docket H054A,'Exhibit 47-27-1 fhttn:/ /dockets.osha.rov/vgOn I/Vp47A/0 1/73/19 p n p i WtBi 49. H ow e SR. The Society of the Plastics Industry Inc: L e tte r to O SH A rtoS/H <?ffice; APril 2. 2005. Docket H0S4A. Exhibit 47-24*1 50. R[bictfhpt.e/r/dCoMck,etHsa.onsnhaap.peol vJ/Sv,fTnhnei /PVoQl4ic7yA/G0r1o/u2p3:/3P6oPsntm-Hearlne C o m ffijK g 3 J K ffl5 !3 S = S & SI ^ p c V R ecords!tHe 52. Final report: Collaborative cohort mortality study of four A o ' i X d P r od"c.tion facilities, m s - W S ^ S u b r n f c t l d by -- n. 53. fm dT ofto 17 t Final rePort: Collaborative cohort mortality mi ^ e H f h A ChrunL r Productln facilities, 1958-1998. Sub- u A PP,ied Epidemiology, Inc. to the Industrial 48e? 2 hrhttU//datr n' SePtember 22, 2002 Docket H054A, Exhibit 54 n t l'i [t o p-//dock^,osha.poy/vrflniA>'047A/nt/i:vt |p p n s t u d v W o I6 ' M,Chaf Wolfe ^ H e x a v a le n t chrom ium 47:980. nC,US' o n s uni ustlf,ed' J Occup Environ M ed 2005, 55. Mundt k, Luippold R, Dell L, Birk T: Reply to Hexavalent chro m ium study s conclusions unjustified. J Occup Environ M ed 2005, 56. e l r - J ' N ^'Su S.K U t t e r to A manda Edens, Occupational c"?, Administration, June 29, 2005.P Docket ^ 5 ^ Exhibit 48-1 [hap;//dpckeB.osha.gov/vBflnl 57. Healihl^Vdm f i! ! ^ andy Edens> Occupational Safety and Health Administration, October 17 2005 u n caa 58. 59. Section 6(b)5, Occupational Safety and Health A c t of P.L. 60. Michaels D, Monforton C: Manufacturing uncertainty con tested science and the protection of the public's health and 61. DeenAvnirgoenlims eCn, tD, rAazmejn PJuMb,HFerailztehll2e00FA5,, 9H5aiSu3g9C-S,48Hoey I, Horton R Kotzin S, Laine C, Marusic A, Overbeke AJ, Schroeder T V Sox H C Van D e r W eyden MB: Is this clinical trial f ^ y registered' A statement from the International Committee of Medical 62. Journal Editors. N EnglJ Med 2005, 352:2436-2438 J a n u ^ 9 2005rUg firm S ' "" `" S " openness- The * * > be . 63. Davidoff F DeAngelis C D , Drazen JM, Hoey j, Hoigaard L Horton R Kotzin S, Nicholls MG, Nylenna M, Overbeke AJ, Sox HC, Van D er eyden MB, Wilkes MS: Sponsorship, Authorship and 64. Accountability. JAMA 2001, 286:1232-1234 P' " 2 0 0 ?3 0 ^ 2 0 7 3 gn6rW : DiSClSUre in u h to ry science. Science 65. W agner W , Michaels D M : Equal treatment for regulatory sci ence, extending the controls governing public research to private research. J Law & Med 2004, 30:119-154, Publish with Bio Med Central and every scientist can read your w ork free of charge BioM ed Central will be the most significant development for disseminating the results o f biomedical research in our lifetime. " Sir Paul Nurse, Cancer Research UK Your research papers will be: available free of chargeto the entire biomedicalcommunity peer reviewed and published immediately upon acceptance o cited in PubMed and archived on PubMed Central yours -- you keep the copyright Submit your m anuscript here: http://www.blo1nedcentral.conVinfQipublishing._adv.a5p BioMedcentral P age 8 of 8 (page number not for citation purposes)