A nano-mesothelioma false alarm

Nanotechnology Law and Business

Volumn 5, Issue 3, 2008, Pages 319-333

  Monica Jr , John C ^a   Monyca, John C ^b  

^a Porter Wright Morris and Arthur LLP   (United States)

^b UNIVERSITY OF VERMONT   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

COURT OF LAWS; DAUBERT; FALSE ALARMS; SCIENTIFIC COMMUNITIES; SCIENTIFIC STUDIES; SPONTANEOUS FORMATIONS;

ALARM SYSTEMS; LAWS AND LEGISLATION; MULTIWALLED CARBON NANOTUBES (MWCN); NANOCOMPOSITES; NANOSTRUCTURED MATERIALS; NANOSTRUCTURES; NANOTUBES; SURFACE CHEMISTRY; TUMORS;

CARBON NANOTUBES;

EID: 56449095444     PISSN: 15462080     EISSN: 15462080     Source Type: Journal    
DOI: None     Document Type: Article

References (103)

1. C. Poland, et al., Carbon Nanotubes Introduced Into The Abdominal Cavity Of Mice Show Asbestos-Like Pathology In A Pilot study, NATURE NANOTECHNOLOGY, May 20, 2008 ("Poland Study"). Along with their paper, the authors also published a document entitled "Supplementary Information" which describes in detail how they conducted the research.
2. The authors define "nanotube" as "a graphene cylinder, typically a few nanometers in diameter, which can range in length from a few nanometers to millimeters." Poland Study, at 1. Single-walled nanotubes consist of one cylinder, while the MWCNTs used in the Poland Study were comprised of "2 to 50 cylinders concentrically stacked with a common long axis." Id.
3. The stated intent of the exclusion issued on September 24, 2008 by Continental Western Insurance Group was to "remove coverage for the yet unknown and unknowable risks created by products and processes that involve nanotubes." The posting of the exclusion together with two explanatory documents on Continental's website was quickly removed the same day after BNA published an article about the exclusion. These documents can be found at http://www.nanolawreport.com/2008/09/articles/first-commercial-insurance- exclusion-for-nanotechnology/.
4. A. Kane, et al., The Asbestos Analogy Revisited, NATURE NANOTECHNOLOGY, Vol. 3, 378-379 (July 2008) ("Kane & Hurt").
5. Poland Study, at 1.
6. Pathogenesis is the origination and development of a disease-called also pathogeny. (Medline Plus Dictionary).
7. A granuloma is a mass or nodule of chronically inflamed tissue with granulations that is usually associated with an infective process. A granulation is a minute mass of tissue projecting from the surface of an organ; one of the minute red granules made up of loops of newly formed capillaries that form on a raw surface (as of a wound) and that with fibroblasts are the active agents in the process of healing. (Medline Plus Dictionary).
8. Poland Study, at 1.
9. The authors make a point of leading off by reiterating "concerns that widespread use of carbon nanotubes may lead to mesothelioma. Poland Study, at 1.
10. Asbestos consists of a group of minerals that occur naturally as masses of strong, flexible fibers that can be separated into thin threads and woven. (National Cancer Institute web definition).
11. Poland Study, at 1.
12. Kane & Hurt, at 378. While acknowledging that the nanotube/asbestos "analogy" exists due to the similarity of the small fiber diameter, long length, and biopresence characteristics of the two substances, Kane & Hurt point out that there are also important differences between these two fibrous materials such as their chemical composition and surface properties.
13. The mesothelium is a "sac-like membrane that protects most of the body's internal organs that is divided into two distinct protective layers of cells: the visceral (the layer directly surrounding the organ) and the parietal (a sac surrounding the body cavity). By releasing a lubricating fluid, the mesothelium allows the organs to move more freely within the body cavity; for example, the contraction and expansion of the lung." (National Cancer Institute web definition).
14. Poland Study, at 2.
15. Id. at 4. Mesothelioma is a relatively rare cancer with approximately 2,000 new cases diagnosed in the United States each year. A history of occupational asbestos exposure is reported in about 70 percent to 80 percent of all cases. (National Cancer Institute web definition).
16. Kane & Hurt in their review of the Poland Study suggest that the normal defense mechanism against foreign materials is accumulation of activated marcrophages and multinucleated giant cells to form a granuloma. They further assert that if the foreign materials are resistant to degradation and cause persistent generation of tissue-damaging free radicals, granulomas can become sites for recruitment of fibroblasts, deposition of collagen scar tissue and in-growth of new blood vessels. Continuing in their attempt to explain the mechanism of disease, Kane & Hurt assert that the free radicals also cause DNA damage and mutations in proliferating cells that are the precursors of mesothelioma. Kane & Hurt, at 379.
17. The following substances were injected into separate mice: long fiber amosite asbestos; short fiber amosite; MWCNTs consisting of a "substantial portion" of long straight fibers; MWCNTs consisting of long tangled MWCNTs; and ultrafine carbon black. Poland Study, at 2.
18. Id. at 2.
19. Id.
20. Id.
21. Id. at 4-5.
22. Id.
23. Id. at 5.
24. Steadman's Medical Dictionary, Williams & Wilkins (1972).
25. Kane & Hurt, at 379.
26. Id.
27. Id.
28. Poland Study, at 1 & 5.
29. Id. at 1.
30. Id. at 6, n. 11 (citing with approval Mossman & Churg, Mechanisms In The Pathogenesis Of Asbestos And Silicosis, AM. J. RESPIR. CRIT. CARE MED., Vol. 157, pp. 1666-1680 (1998) ("Mossman Article")).
31. Poland Study, at 1 & 5.
32. Poland Study, at 5.
33. Kane & Hurt, at 378-79.
34. Id.
35. See Toxicity Tests in Animals: Extrapolating to Human Risks, ENVIRONMENTAL HEALTH PERSPECTIVES, Vol. 101, No. 5 (Oct. 1983); P. Shubik, The Validity of Animal Studies with Chemical Carcinogens, CA CANCER J. CLIN., 1981; 31; 120-123.
36. Kane & Hurt, at 378-379 (July 2008).
37. Poland Study, Supplementary Information, "Experimental Animals", at 4.
38. Kane & Hurt, at 379.
39. Id.
40. Poland Study, at 3.
41. Infections granulomas are defined as any granulomatous lesion caused by a living agent including bacteria, fungi, helminths, etc. Stedman's Medical Dictionary, Williams & Wilkins (1972).
42. M. Mahler, et al., "Health Monitoring in the Laboratory Mouse," edited by Hans Elsevier, Academic Press (2004).
43. Poland Study, at 3.
44. Id. at 1.
45. Mossman Article, at 1670.
46. Id. at 1670-1671.
47. Poland Study, at 1.
48. Mossman observed: "Epidemiologic studies indicate very clearly that the development of asbestosis requires heavy exposure to asbestos and provide strong evidence that there is a threshold fiber dose below which asbestos is not seen." Further: "[T]he lower the exposure, the longer it takes to reach this threshold in workplace settings." Mossman Article, at 1667.
49. Mossman Article, at 1672.
50. Poland Study, at 2.
51. The dose-response relationship between a substance and the reaction it causes in the human body is very important. Dose-response analysis usually involves an extrapolation from the generally high doses administered to experimental animals or exposures noted in epidemiologic studies to the much lower exposure levels expected from normal human contact with the agent. Positive studies above the maximum tolerated dose (MTD) must be carefully reviewed to ensure that the responses are not due to factors inoperative at exposure levels below the MTD.
52. Poland Study, at 2.
53. Id. at 4.
54. Mossman observed: The geometry and dimensions of these (asbestos) materials may govern their deposition and clearance kinetics, biologic reactivity, and dissolution in the lung, but chemical and surface properties, including sorption, oxidation/reduction reactions, and charge, also play important roles in biopersistence, cellular responses, and pathogenicity. [S]urface chemistry is important in driving oxidant production and possibly other deleterious reactions in the lung that are linked to the advent of inflammation and fibrogenesis." Mossman Article, at 1668, 1675.
55. Poland Study, at 2.
56. Equally curious is the fact that this sample did not truly consist of nanoscale materials. The mean diameter of the particles in this sample was 165.02 + 4.68 nanometers. Approximately 85% of those particles were greater than 15 micrometers in length. Poland Study, at 2, figure 1. Commonly accepted standards require at least one dimension of the particle be less than 100 nanometers in length for the material to be deemed "nanoscale."
57. Poland Study, at 2, Table 1.
58. Id.
59. The Poland Study concludes that only long-fiber nanotubes cause granulomas but admits that a "small insignificant" granuloma response was also found in one of the three mice injected with the tangled/short sample. The authors speculate that this may have been caused by either contamination of the short-fiber sample with long fibers, spontaneous occurrence of granulomas by "chance," or an unidentified substance such as a metal contaminating the nanotube test samples. The Poland Study also observes that "transitional metals" were implicated in CNT-mediated stress in an earlier study published on nanotubes.
60. Poland Study, Supplementary Information, at 3.
61. Id.
62. Mossman Article, at 1669.
63. Poland Study, at 2, Table 1.
64. Id.
65. Id.
66. Id.
67. Id.
68. There was some attempt to remove the contaminating metals contained within the samples which the study first states produced "no significant" inflammatory effects 24 hours after injection" but then admits a "remote possibility" that some unmeasured metal or other component could have contributed to the difference in the peritoneal response observed between long and short MWCNTs. One might legitimately raise a question as to whether 24 hours is long enough to wait for inflammation to develop.
69. Mossman Article, at 1669.
70. Poland Study, at 3-4.
71. Id. at 4.
72. Id.
73. Poland Study, Supplementary Information, at 1.
74. Id.
75. Id.
76. Id.
77. Kane & Hurt, at 379.
78. C. Smith, Peering into the Microscope: the Rise of Judicial Gatekeeping After Daubert and Its Effect on Federal Toxic Tort Litigation, 13 B. U. J. SCI. & TECH. L. 218, 218 (2007).
79. Fed. R. Evid. 702.
80. See Daubert v. Merrell Dow Pharmaceuticals, Inc., 509 U.S. 579 (1993).
81. See Id.
82. See Id.
83. See Id.
84. See Id.
85. See General Elec. Co. v. Joiner, 522 U.S. 16, 146 (1997).
86. See Claar v. Burlington N.R.R., 259 F. 3d 499 (9th Cir. 1994).
87. Daubert v. Merrell Dow Pharmaceuticals, Inc., 509 U.S. 579 (1993).
88. S. Loomis, The Daubert Test of Reliability: Fighting 'Junk Science' in the Courtrooms, http://www.skepticreport.com/skepticism/dauberttest.htm (citing North Dallas Diagnostic Center v. Dewberry, 900 S. W. 2d 90, 95 (Tex. App.-Dallas 1995, writ denied)).
89. Id. (citing Merrell Dow Pharmaceuticals, Inc. v. Havner, 953 S.W.2d 706, 714 (Tex. 1997)).
90. In Re Paoli R. R. Yard PCB Litigation, 35 F.3d 717, 745 (3d Cir. 1994).
91. Kane & Hurt, at 378-379.
92. Mossman Article, at 1670.
93. Id. at 1670-1671.
94. Rider v. Sandoz Pharmaceuticals Corp., 295 F.3d 1194, 1202 (11th Cir. 2002).
95. Id.
96. Moore v. Ashland Chemical, Inc., 151 F.3d 269, 272 (5th Cir. 1998).
97. Allen v. Pennsylvania Engineering Corp., 102 F.3d 194, 197 (5th Cir. 1996).
98. General Electric Co. v. Joiner, 522 U.S. 136, 143-44 (1997) (citing Turpin v. Merrell Dow Chemical, Inc, 959 F.3d 1349, 1360 (6th Cir. 1992)); see also Moore v. Ashland Chemical, Inc., 151 F.3d 269, 272 (5th Cir. 1998); Mitchell v. Gencorp Inc., 165 F.3d 778, 782 (10th Cir. 1999).
99. General Electric Co. v. Joiner, 522 U.S. 136, 143-44 (1997).
100. See Karte v. Exxonmobil Coal USA, Inc., 164 Fed. Appx. 553, 556 (7th Cir. 2006) (excluding evidence because expert failed to properly consider and exclude possible alternative causes "such as seasonal allergies, pesticides, or cigarette smoking.").
101. While many state courts have adopted the same analysis as federal courts, some use an older, more general test. In those jurisdictions, scientific evidence is admissible if it is based on science generally accepted as reliable in the scientific community. Frye v. United States, 293 F. 1014 (D.C. Cir. 1923). We reach the same conclusions applying this broader test.
102. One of the Poland Study's findings was that short and tangled nanotubes did not cause either inflammation or granulomas. Poland Study, at 4. Thus, it might arguably be used to absolve short and tangled nanotubes from having an adverse health impact on mice (or humans). The difficulty of using the Poland Study to extrapolate to other nanotubes due to the limited nature of its findings is also recognized by Kane " Hurt.
103. Susan R. Morrissey, Challenge of Risk-Based Nanotech Research, CHEMICAL & ENGINEERING NEWS (Oct. 15, 2007) (quoting Dr. Kristen Kulinowski, Director of the International Council on Nanotechnology at Rice University).