Full opinion text
MEMORANDUM OPINION AND ORDER EISELE, District Judge. Before the Court is defendant Associated Milk Producers, Inc.’s (“AMPI”) Motion to Exclude Opinion Testimony of Plaintiffs Experts and defendant’s Motion for Summary Judgment. The parties have thoroughly briefed this issue. Furthermore, the Court held a hearing on the issue January 7-13, 1998, at which many of the experts for the parties testified. This testimony supplemented the summary judgment submissions previously filed. Thereafter, on January 29, 1998, the Court heard the oral arguments of counsel. AMPI files its motion to exclude plaintiff, John McDougal’s (“plaintiff’), causation experts, contending that their proffered testimony fails to meet the standards set forth in Federal Rules of Evidence 702 and 703, Daubert v. Merrell Dow Pharmaceuticals, Inc., 509 U.S. 579, 113 S.Ct. 2786, 125 L.Ed.2d 469 (1993), and its progeny. AMPI seeks to exclude the testimony of Dr. Jimmie L. Valentine, Dr. Charles Fowler, Dr. Maly Mazumder, Dr. Alex Pappas, Dr. Brad H. Pollock, and Dr. Daniel T. Teitelbaum. These witnesses are being offered to opine regarding several issues crucial to this lawsuit, namely: the occurrence of aflatoxin M-l (hereinafter “AFM”) in milk sold by AMPI during a fifteen month period in 1990 and 1991, whether AFM causes laryngeal cancer in humans, and, if so, at what levels of exposure and dose. Plaintiff asserts he was subjected to AFM-contaminated milk. He contends, first, that under accepted scientific principles, he is not required to prove the dose of AFM to which he was exposed because there is no safe threshold, since one molecule of AFM could cause his cancer under the “one shot” theory. Alternatively, he argues that he has produced sufficient evidence of both his exposure to AFM and the dose he experienced. After exhaustively reviewing the record before it, the Court is ready to rule on defendant’s motions. For the reasons set forth in this Memorandum Opinion, the Court will grant defendant’s motion to exclude and, as a consequence, it will also have to grant defendant’s motion for summary judgment. I. BACKGROUND This diversity case alleges causes of action under Arkansas law based on the tort of outrage, strict liability, breach of implied and express warranties, fear of future conse-quenees and reckless and culpable negligence. From approximately July 26, 1990 until October 31, 1991, John McDougal worked in the Batesville, Arkansas, cheese manufacturing plant of Hills Valley Foods (“HVF”). HVF is an Arkansas corporation which bought milk from distributors and processed that milk into cheese and cheese curd. AMPI, a Kansas corporation, distributed milk in Arkansas (among other states), and supplied HVF with some of the milk it used to make cheese and curd. During his employment at HVF, plaintiff worked on the cheese production line and was allowed to consume cheese freely. Besides ingestion, it is undisputed that plaintiff was exposed to some quantity of milk via inhalation of aerosolized milk particles that were produced by the cheese making process. After suffering from hoarseness for approximately six weeks, plaintiff first presented for treatment on February 27, 1995. He was diagnosed as having laryngeal cancer. He then had surgery to remove half of his voice box and vocal cords on March 6, 1995. He subsequently underwent additional surgeries. Plaintiff asserts that, in June of 1995, he learned that certain AMPI employees had pled guilty in federal court to the distribution of, and conspiracy to distribute, contaminated milk in interstate commerce. This was the first notice he had of such contamination. Plaintiff alleges he developed laryngeal cancer because AMPI provided HVF with AFM-contaminated milk to which he was exposed at his workplace. The tainted milk allegedly was utilized by HVF as a result of the falsification and alteration of test results designed under a regulatory regime to determine the quality of milk. Plaintiff alleges that AMPI redirected to HVF certain shipments of milk that had tested positive for AFM. AFM is a natural by-product of aflatoxin B-l (“AFB”), a substance occasionally found in grains, corn, peanuts, and other food products which often are used to feed cattle. When cows consume AFB-contaminated feed, their systems break down the aflatoxin B-l into the metabolite AFM, which they excrete in their milk. Plaintiff alleges he was exposed to AFM through eating cheese, by inhaling both “dried” and liquid aerosol milk particles produced by the cheese making process at HVF, and by dermal exposure. Plaintiff has named AMPI as the only defendant in this lawsuit. Although plaintiff earlier relied on the opinion that his laryngeal cancer was caused by his exposure to aflatox-in through his eating of aflatoxin-tainted cheese, it is now clear that he is relying upon the theory that aflatoxin inhaled in aerosol form was the cause of his cancer. In any event, plaintiff does not now rely upon any expert opinion that his exposure to aflatoxin through his skin or from eating or drinking-contaminated cheese or milk caused his laryngeal cancer. However, he does still contend that his eating of contaminated cheese forms a legal basis for his fear of future cancer such as hepatic (liver) cancer. Defendant filed its motion to exclude plaintiffs experts’ causation testimony, asserting that the testimony fails to meet Daubert’s admissibility requirements. Prior to the January 7, 1998 hearing on the issue, AMPI contended that plaintiffs experts’ testimony did not constitute “scientific knowledge” and that their theories and methodologies had no general acceptance in the scientific community. AMPI argued that plaintiff must, but cannot, establish: (1) the level of exposure to AFM that is hazardous to human beings generally; (2) that such level of exposure causes the type of injury (laryngeal cancer) of which plaintiff complains; and (3) that John McDougal was exposed while working at HVF to such level of AFM from the milk sold by AMPI to Hills Valley Farms. Quoting Cavallo v. Star Enter., 892 F.Supp. 756 (E.D.Va.1995), defendant has maintained pri- or to, and after, the Daubert hearing that “toxicity is a function of dose. Thus, the question for causation purposes is: At what levels of exposure do what kinds of harm occur?” After the hearing on this issue, the Court is convinced that it must conduct a two pronged analysis. First, the cornerstone issue is whether plaintiff may proceed under a “no-threshold” or “one-hit” theory (hereinafter “no-threshold”). Under a no-threshold approach, plaintiffs experts maintain that there exists no safe level of exposure to genotoxins in general, and AFM in particular. Consequently, they posit that exposure to as little as one molecule of aflatoxin can produce alterations in genetic material leading to cancer. Defendant argues this approach fails to meet the Daubert admissibility standard even if the underlying scientific, biologic theory has acceptance. See discussion below. Alternatively, if the Court rejects the no-threshold theory, the inquiry turns to whether AFM causes laryngeal cancer in humans, and if so at what dose. If plaintiff has admissible evidence on those issues, the question becomes whether Mr. McDougal was subjected to a sufficient dosage to have caused his laryngeal cancer. Defendant’s argument is: “It is simply that there is not evidence in any medical literature or studies that aflatoxin (and particularly aflatoxin M-l which is the metabolite to which Mr. MeDou-gal was allegedly exposed) causes laryngeal cancer such as Mr. McDougal had. They also fail to prove, even if aflatoxin M-l were assumed to cause laryngeal cancer, the level of exposure at which it would do so or the level of Mr. McDougal’s exposure.” II. DISCUSSION A The Daubert Standard Of course, Daubert provides the starting point when a district court undertakes its “gatekeeper role” in determining the admissibility of proffered scientific testimony. This Court provided an extended presentation of what Justice Blackman’s opinion requires of trial courts in National Bank of Commerce v. Dow Chemical Co., 965 F.Supp. 1490 (E.D.Ark.1996), aff'd 133 F.3d 1132 (8th Cir.1998). The Court quotes extensively from its opinion in that case in order to put its analysis of the evidence in its doctrinal context: We start with Justice Blackmun’s opinion in Daubert. After concluding that the Frye Rule (“that austere standard”) should not be applied in federal trials, Daubert, 509 U.S. at 589, 113 S.Ct. at 2794, Justice Blackmun went on to discuss the proper test for admissibility of scientific evidence. He pointed out that Rule 702 nowhere refers to the “general acceptance” test of Frye. He then explained as follows: That the F'i'ye test was displaced by the Rules of Evidence does not mean, however, that the Rules themselves place no limits on the admissibility of purportedly scientific evidence. Nor is the trial judge disabled from screening such evidence. To the contrary, under the Rules the trial judge must ensure that any and all scientific testimony or evidence admitted is not only relevant, but reliable. The primary locus of this obligation is Rule 702, which clearly contemplates some degree of regulation of the subjects and theories about which an expert may testify. “If scientific, technical, or other specialized knowledge will assist the trier of fact to understand the evidence or to determine a fact in issue” an expert “may testify thereto.” The subject of an expert’s testimony must be “scientific ... knowledge.” The adjective “scientific” implies a grounding in the methods and procedures of science. Similarly, the word “knowledge” connotes more than subjective belief or unsupported speculation. The term “applies to any body of known facts or to any body of ideas inferred from such facts or accepted as truths on good grounds.” Webster’s Third New International Dictionary 1252 (1986). Of course, it would be unreasonable to conclude that the subject to scientific testimony must be “known” to a certainty; arguably, there are no certainties in science. * * * * * * But, in order to qualify as “scientific knowledge,” an inference or assertion must be derived by the scientific method. Proposed testimony must be supported by appropriate validation — i.e., “good grounds,” based on what is known. In short, the requirement that an expert’s testimony pertain to “scientific knowledge” establishes a standard of evidentiary reliability. Daubert, 509 U.S. at 589-90, 113 S.Ct. at 2794-95 (emphasis in original). It is important also to consider Justice Blaek-mun’s footnote to this observation: We note that scientists typically distinguish between “validity” (does the principle support what it purports to show?) and “reliability” (does application of the principle produce consistent results?). i|s ‡ :¡: :*i :¡t *5* ... our reference here is to evidentiary reliability — that is, trustworthiness. In a case involving scientific evidence, evidentiary reliability will be based upon scientific validity. Id. at n. 9. The majority opinion then goes on to state that: Rule 702 further requires that the evidence or testimony “assist the trier of fact to understand the evidence or to determine a fact in issue.” This condition goes primarily to relevance. “Expert testimony which does not relate to any issue in the case is not relevant and, ergo, non-helpful.” Ht & sic í-í 45 Rule 702’s “helpfulness” standard requires a valid scientific connection to the pertinent inquiry as a precondition to admissibility. That these requirements are embodied in Rule 702 is non surprising. Unlike an ordinary witness, see Rule 701, an expert is permitted wide latitude to offer opinions, including those that are not based on firsthand knowledge or observation. See Rules 702 and 703. Presumably, this relaxation of the usual requirement of first-hand knowledge — a rule which represents “a ‘most pervasive manifestation’ of the common law insistence upon ‘the most reliable sources of information.’ ” Advisory Committee’s Notes on Fed.Rule Evid. 602 (citation omitted) — is premised on an assumption that the expert’s opinion will have a reliable basis in the knowledge and experience of his discipline. Daubert, 509 U.S. at 591-92, 113 S.Ct. at 2796. With this doctrinal background in mind, Justice Blackmun then provides the trial judge with practical instructions on how to proceed when expert scientific testimony is challenged: Faced with a proffer of expert scientific testimony, then, the trial judge must determine at the outset, pursuant to Rule 104(a), whether the expert is proposing to testify to (1) scientific knowledge that (2) will assist the trier of fact to understand or determine a fact in issue. This entails a preliminary assessment of whether the reasoning or methodology underlying the testimony is scientifically valid and of whether the reasoning or methodology properly can be applied to the facts in issue. We are confident that federal judges possess the capacity to undertake this review. Many factors will bear on'the inquiry, and we do not presume to set out a definitive checklist or test. But some general observations are appropriate. Ordinarily, a key question to be answered in determining whether a theory or technique is scientific knowledge that will assist the trier of fact will be whether it can be (and has been) tested. “Scientific methodology today is based on generating hypotheses and testing them to see if they can be falsified; indeed, this methodology is what distinguishes science from other fields of human inquiry.” Green at 645. See also C. Hempel, Philosophy of Natural Science 49 (1966) (“[T]he statements constituting a scientific explanation must be capable of empirical test”); K. Popper. Conjectures and Refutations: The Growth of Scientific Knoivledge 37 (5th Ed.1989) (“[T]he criterion of the scientific status of a theory is its falsifiability, or refutability, or testability”). Another pertinent consideration is whether the theory or technique has been subjected to peer review and publication. Publication (which is but one element of peer review) is not a sine qua non admissibility; it does not necessarily correlate with reliability, see S. Jasa-noff. The fifth Branch: Science Advis-ors as Policymakers 61-76 (1990), and in some instances well-grounded but innovative theories will not have been published, see Horrobin, The Philosophical Basis of Peer Review and the Suppression of Innovation, 263 JAm.Med. Assn. 1438 (1990). Some propositions, moreover, are too particular, too new, or of too limited interest to be published. But submission to the scrutiny of the scientific community is a component of “good science,” in part because it increases the likelihood that substantive flaws in methodology will be detected. See J. Siman, Reliable Knowledge: An Exploration of the Grounds of Belief in Science 130-133 (1978); Reiman and An-gelí, How Good Is Peer Review?, 321 New Eng.J.Med . 827 (1989). The fact of publication (or lack thereof) in a peer-reviewed journal thus will be relevant, though not dispositive, consideration in assessing the scientific validity of a particular technique or methodology on which an opinion is premised. Additionally, in the case of particular scientific technique, the court ordinarily should consider the known or potential rate of error, see, e.g., United States v. Smith, 869 F.2d 348, 353-364 (7th Cir.1989) (surveying studies of the error rate of spectrographic voice identification technique), and the existence and maintenance of standards controlling the technique’s operation. See United States v. Williams, 583 F.2d 1194, 1198 (2d Cir.1978) (noting professional organization’s standard governing spectro-graphic analysis), cert. denied, 439 U.S. 1117, 99 S.Ct. 1025, 59 L.Ed.2d 77 (1979). Finally, “general acceptance” can yet have a bearing on the inquiry. A “reliability assessment does not require, although it does permit, explicit identification of a relevant scientific community and an express determination of a particular degree of acceptance within that community.” United States v. Downing, 753 F.2d at 1238. See also 3 Weinstein & Berger ¶ 702[03], pp. 702-41 to 702-42. Widespread acceptance can be an important factor in ruling particular evidence admissible, and “a known technique that has been able to attract only minimal support within the community,” Downing, supra, at 1238, may properly be viewed with skepticism. The inquiry envisioned by Rule 702 is, we emphasize, a flexible one. Its overarching subject is the scientific validity — and thus the evidentiary relevance and reliability — of the principles that underlie a proposed submission. The focus, of course, must be solely on principles and methodology, not on the conclusions that they generate. Daubert, 509 U.S. at 592-95, 113 S.Ct. at 2796-97. The DaubeH opinion also instructs the trial judge to be mindful of the provisions of Rules 703, 706 and 403. Finally, the trial judge is admonished that if she or he concludes that a scintilla of evidence supporting a position is insufficient to allow a reasonable jury to conclude that the position is more likely than not true, the court remains free to direct a judgement, see Fed.Rule Civ.Proc. 50(a), and likewise to grant summary judgment, Fed. Rule Civ.Proc. 56. This is to remind us that scientific evidence may raise questions not only as to admissibility but also as to sufficiency. It is interesting to note that Justice Blackmun cites the case of Brock v. Merrell Dow Pharmaceuticals, Inc., 874 F.2d 307 (5th Cir.1989), modified, 884 F.2d 166 (5th Cir.1989), in support of this proposition. In summary, Justice Blackmun states that the rules of evidence (especially Rule 702). ... do assign to the trial judge the task of ensuring that an expert’s testimony both rests on a reliable foundation and is relevant to the task at hand. Pertinent evidence based on scientifically valid principles will satisfy those demands. Daubert, 113 S.Ct. at 2799. Daubert holds that admissibility under Rule 702 is governed by Rule 104(a), which requires the judge to conduct “preliminary fact-finding, to make a preliminary assessment of whether the reasoning or methodology underlying the testimony is scientifically valid and whether that reasoning or methodology properly can be applied to the facts in issue.” Id. at 2796. Thus, before admitting scientific evidence, the Court must, inter alia, determine whether the theory advanced by the expert has been subjected to the “scientific method.” Id. at 2795, 2797. And the focus of this inquiry must be on “principles and methodology, not on the conclusions that they generate.” Daubert, at 2797. “Scientific validity” and “fit” inquiries may overlap. For example, if published theories and studies purport to prove A, yet from those studies an expert concludes B, it may be that the expert’s reasoning process is not valid, although the studies or theories she relies upon are. In sum, there may be a lack of “fit” between the studies and theories and the conclusion the expert draws from them. Each step of the experts’ methodology must be scientifically valid. See In re Paoli R.R. Yard PCB Litigation, 35 F.3d 717, 745 (3d Cir.1994). For example, in a situation where an expert relies on studies of the effects of animal exposure to a particular chemical to prove similar effects in humans, “[cjourts must assess the scientific validity of the hypothesis proffered to justify such an extrapolation.” Developments in the Law — Confronting the New Challenges of Scientific Evidence, 108 Harv.L.Rev. 1481, 1536 (1995).’ National Bank of Commerce v. Dow, 965 F.Supp. at 1493-96. Whether proceeding on a negligence or strict liability theory, a plaintiff in a toxic tort case must, under Arkansas law, establish medical causation through expert testimony. See Southern Co., Inc. v. Graham, 271 Ark. 223, 607 S.W.2d 677, 679 (1980) and 327 Ark. 367, 937 S.W.2d 183 (1997). Under Wright v. Willamette Indus., Inc. ., 91 F.3d 1105 (8th Cir.1996), a plaintiff must show proximate causation and, among other things, that it is more likely so than not so that another party has caused him harm. It is not enough to show that a suspect chemical agent sometimes causes the kind of harm complained of. This Eighth Circuit precedent arguably negates plaintiffs “no threshold” theory. Nevertheless, the Court will deal with that theory upon the hypothesis that it is not entirely foreclosed by Wright. The Supreme Court recently reaffirmed the importance of the district court’s gatekeeper role in General Electric v. Joiner, — U.S. -, 118 S.Ct. 512, 139 L.Ed.2d 508 (1997). There, the Supreme Court addressed the standard of review in cases which hinge on a Daubert analysis. In Joiner the District Court excluded under Daubert the plaintiffs proffered expert testimony. Id. at 516. Applying a “particularly stringent standard of review to the trial judge’s exclusion of expert testimony,” the Eleventh Circuit reversed the trial court’s decision. Id. The Supreme Court then reversed the Eleventh Circuit’s decision holding that “abuse of discretion,” the standard applicable to evidentiary rulings, is the proper standard by which an appellate court reviews a district court’s decision to admit or exclude expert opinion testimony after a Daubert hearing. The Supreme Court held that the trial court did not abuse its discretion and, therefore, reversed the Court of Appeals’ decision. Id. at 517-18. While this Court appreciates the Supreme Court’s vote of confidence in the ability of United States District Judges to discharge their duties under Daubert, it would nonetheless welcome the critical appellate review of its decisions in this complex, difficult, and developing area of the law. This is particularly so when the trial court’s rejection of a plaintiffs proffered scientific causation evidence results in the dismissal of the lawsuit, i.e., is outcome determinative, thus raising Seventh Amendment concerns. B. Cancer — A Genetic Disease A brief description of cancer as a disease and its usual development stages is necessary. The Court will utilize the testimony of one of the plaintiffs experts for this purpose. Dr. Teitelbaum testified (as set forth in the textbook Molecular Oncology) that cancer is a genetic disease. He states that “it is the sequence of genetic events which occur, plus those epigenetic; that is, non-genetic but promotional events which occur in the right order which ultimately result in the development of cancer as a clinical disease.” (Tr. Vol. 2, p. 25 Daubert hearing). He states that “without the genetic changes, you don’t have cancer.” Id., p. 26. But, he acknowledges that some people have an “innate defect which pre-programs them to cancer,” and that there may be cancers which are purely genetic. Id. Dr. Teitelbaum drew a distinction between carcinogens that are mutagens and those that are promoters. Human carcinogens that are mutagens include x-rays, aflatoxin, and PAHs in tobacco. On the other hand, estrogen in breast cancer probably results from its promoter activity on breast tissue. So he distinguishes genotoxie carcinogens, those which directly affect the DNA, from epigenesis or promotional carcinogens, which change the growth patterns without necessarily changing the DNA. Aflatoxin is a mutagen genotoxie carcinogen. Dr. Teitlabaum’s testimony on the development of cancers is informative: That’s correct. And the whole process of development of cancer is an orderly progression from a normal cell to an initiated cell; the initiated cell has had a genetic hit. It is primed and ready to become cancer, but unless something further happens to it, it will not become cancer. That initiated cell takes further hits, and each of those hits moves the disease along. Ultimately enough hits are accumulated so that the cell possesses all the characteristics that we would call a cancer, capacity to invade other tissues, the capacity to produce its own blood supply, the capacity to break off and metastasize and set up shop in another tissue. Each of those characteristics requires a genetic hit. It requires a fundamental change in what is basically an ordinary process. That is, the growth of cells is ordinarily, under ordinary circumstances, we have billions of cells. They behave properly most of the time. One cell becomes a rogue because it has had a series of hits, a series of promotional events, it becomes cancer. Now, as each of these hits takes place and the cell multiplies, the target for the next hit is larger. And therefore each successive hit is far more probable than the early hit, which is why cancer tends to be a disease of older persons who have had a whole series of events which have taken place in their lives which permit the aging of the cell. Tr. Yol. 2, at 30-31. Dr. Teitlebaum also explained, “DNA ad-ducts” and epoxides: Now, we’ve gotten very much smarter in that we can do molecular studies. In this case there’s been all kinds of discussion about DNA adducts and so on. The DNA adduct is absolute evidence of an interaction between DNA and the carcinogen. If you are able to do that, typically if you do that, let’s say, with ethylene oxide, we can show that ethylene oxide binds to DNA. The patient doesn’t have cancer, but the patient clearly has had a DNA impact. That could have been done. Some of that work has been done, in fact, at the University of Arkansas on DNA adducts for various materials. In animals, DNA adducts for aflatoxin have been shown in tracheal tissue and nasal tissue and laryngeal tissue. THE COURT: Technically, what does that mean? You take the ordinary DNA— A. Right. THE COURT: And now you look at it again after this event. And what do we observe? A. What you now observe is that attached to the DNA is a metabolite of the chemical compound which you give. Now, again, in this case there’s been a lot of discussion about the activation of aflatoxin. Aflatoxin per se is not the problem. Activated afla-toxin is the problem. BY MR. DAVIDSON: Q. That’s the epoxide? A. That’s the epoxide. Epoxides are extraordinarily reactive. Because of the presence of the oxygen with the rather unstable bond, it is possible for that substance to bind to many large molecules. Some of what it does when it binds is to kill the liver cells. We know that aflatoxin causes toxic hepatitis and will kill in humans and in animals. We also know that the activated aflatoxin, whether it is B1 or Ml, can bind to DNA and can cause cancer in animals. Now, we know that the tissues of interest in this ease, upper airway tissues, squamous epithelium in the larynx, squamous epithelium in the nose, have been looked at both in animals and in humans for their capacity to activate carcinogens. And they do activate carcinogens, very actively. As I say, some of that work was done here in Arkansas. So you take a normal cell. You add the carcinogen. The cell activates it. You may not, looking at that cell under the microscope, be able to tell that anything has happened. But if you go to a process like autoradiograpy, which shows where the binding has taken place by having a radioactive molecule now incorporated in the DNA, you can show the carcinogen has, in fact, affected the DNA. That’s been shown with aflatoxin, with all of the afla-toxins that we are talking about, Ml and Bl. ‡ ‡ ‡ ‡ THE COURT: And there won’t be any cancer from a known carcinogen unless that particular tissue has the epoxide that will activate it? A. It not only has to have the epoxide, but it also has to go through this. The cell cannot die as a result of it. It has to multiply and be able to live the rest of the way. Otherwise, you don’t get cancer. THE COURT: Are each and every one of these epoxides specific to the specific carcinogen; in other words, or if you have the epoxide in the larynx tissue, any carcinogen will activate? A. You can’t say any carcinogen because there are a whole series of monooxygenas-es, some of which work on particular structures. But it appears that the capacity to active aflatoxin does exist in upper airway tissues. Tr. Vol. 2, at 35-37. Next we turn to a closer look at the particular disease at issue here: laryngeal cancer. C. Larynx Cancer in Humans Plaintiffs expert, Dr. Daniel T. Teitel-baum, testified that approximately seventy-five to ninety percent of the larynx cancers in humans are caused by smoking tobacco. Other potential causes he listed include metal working fluids, rayon, alcohol, asbestos, and substances common to the rubber industry. Even though smoking tobacco is recognized as the major cause of laryngeal cancer, it appears that there have been no studies indicating whether second hand or “side stream” tobacco smoke has been associated with that form of cancer. Since there have been no confirmatory studies showing that the inhalation of second hand or sidestream tobacco smoke causes laryngeal cancer, Dr. Teitel-baum would rule it out here even though there was evidence that Mr. McDougal was exposed to such tobacco smoke and even though the actual smoking of tobacco is known to cause 75% to 90% of all laryngeal cancers. See infra. Dr. Teitelbaum also stated that certain allergies may have a co-carcinogenic effect with other substances, a factor which he did not rule out in plaintiffs case. See discussion below. After receiving and reviewing all the parties’ submissions, testimony, and argument, the Court finds that there is no scientific literature drawing a direct connection between the inhalation of vapors containing AFM (or any other exposure to AFM) and the occurrence of laryngeal cancer in humans. Neither party has proffered any study, experiment, or other publication in which any exposure to AFM was found to cause laryngeal cancer in humans. Moreover, there is no scientific evidence showing that the much more potent aflatoxin B-l causes larynx cancer in humans. Where there is no direct scientific knowledge that a particular substance causes a particular form of cancer in humans, experts must turn to epidemiological studies, in vitro studies, animal studies, and other indirect methods in an attempt to make the connection. Here, there are no such studies in which AFM or AFB have been shown to cause cancer of the larynx. (See discussion, infra). These findings and conclusions are enough to sustain plaintiffs Daubert causation motion, but the draconic consequences of such a ruling (dismissal of the ease) counsel more discussion. D. Aflatoxins — A review of the history of their study and an assessment of the status of our current knowledye. It is the Court’s opinion that the Daubert issues presented in this case cannot be adequately dealt with absent an understanding of aflatoxins. Dr. Frances Ann Draughon, Professor of Food Microbiology and Toxicology in the Department of Food Science and Technology at the University of Tennessee, impressed the Court as the most knowledgeable expert in this case on the subject of aflatoxins. She is one of the defendant’s experts. Dr. Draughon joined the faculty at the University of Tennessee in 1979 immediately upon receiving her doctorate degree from the University of Georgia. She currently teaches food microbiology lecture and lab, advanced microbiology and food toxicology. She is a member of the faculty of Biotechnology and serves as a committee member on the University’s Environmental Toxicology Program. Dr. Draughon has won several awards for her research work. Her research has dealt with mycotoxins (mold toxins) since 1973 and her primary study has been with aflatoxins. She has also authored numerous publications on other mycotoxins. Her current research is aimed at reducing aflatoxin levels in foods and feeds through biodegradation or bior-emediation using enzymes obtained from various organisms. She considers her primary expertise to be in aflatoxins and food safety. From Dr. Draughon’s report of September 17, 1997, entitled “Aflatoxins in Milk and Other Foods, Biological Activity, Occurrence and Regulation,” and from her testimony in this proceeding the Court has obtained an immense amount of information concerning aflatoxins, most of which is not challenged by plaintiff. The “afla” portion of the word aflatoxin comes from the name of the organism Asper-gillus Flavus which was found to produce toxins in feedstuffs in the early 1960’s. In 1960 over 500 poultry farms in the United Kingdom lost over 100,000 turkey poults due to a mysterious disease called turkey “X” disease. The disease was quickly linked to peanut meal used in the feeds on those farms. A toxic chemical compound was isolated from the Aspergillus Flavus mold in the peanut meal. It was named aflatoxin and designated B-l because of the blue fluorescence of the chemical. Over the years studies have revealed that there are hundreds of naturally occurring toxins which are produced by the growth of mold on foods and feeds. However, only a few have been extensively studied. According to Dr. Draughon, aflatoxins are the most widely studied of the mycotoxins. She states that over 5,000 research papers have been published on the occurrence, analysis, toxicity, mutagenicity and carcinogenicity of afla-toxins. Much progress has been made in the understanding of these properties of aflatox-ins and also of them “target organs” and the biosynthesis of such compounds. According to Dr. Draughon the term “afla-toxins” refers to 18 different aflatoxins which are produced by the molds Aflavus, Aparar siticus or A.nominus or which are metabolites thereof or detoxification products. In this case we are dealing with aflatoxin M-l, a metabolite produced through animal metabolism from aflatoxin B-l. In her report, Dr. Draughon illustrates the differences in the chemical structures of these toxins. Although the structure activity relationship provides a method of predicting toxicity in new chemicals, that approach has serious limitations. As an example, she notes that benzene and toluene and ethel benzene have similar structure activity relationships. Nevertheless, benzene is highly associated with leukemia whereas the other two are not. She states that a similar situation exists with aflatoxins. “Some are highly toxic and carcinogenic, others are not. Fortunately, we do not have to ‘guess’ as to their mutagenicity since aflatoxins are not ‘new’ chemicals and extensive toxicity and mutagenicity testing have been done to determine which are most hazardous.” Id at 4. She goes on to state, “since some aflatoxins are extremely toxic and/or carcinogenic and others have no toxicity or carcinogenicity it is important to distinguish as to which aflatoxin is being referred to when we discuss aflatoxins.” Id at 4. She sets forth a chart which shows the relative mutagenicity of some twelve aflatox-ins ranging from 100 for aflatoxin B-l to 0 for aflatoxin G-2a. According to the Ames test aflatoxin M-l, with which we are here concerned, is given a relative mutagenicity of 3. This would indicate that aflatoxin M-l has only about 3% of the mutagenicity and carcinogenicity potential of aflatoxin B-l. Other documents and experts have placed the relative mutagenicity of AFM when compared to AFB as being in the range of 31 to 10%. It is important to understand the history of the effort of governmental agencies to regulate aflatoxins. In 1965 the FDA under the Food, Drug and Cosmetic Act established an information action level of 30 ppb for peanuts. Since then it has established action levels for aflatoxins in a variety of food products. Today the action level for aflatoxin M-1 for milk is 0.5ppb. Ten ppb has been established for aflatoxin B-l, B-2, G-l and G-2 for all foods except milk and for the feed for dairy cattle. The Action Level for feed for dairy cattle is twenty ppb. AFM is produced by dairy cows that eat food contaminated with AFB. A relationship can be seen between the action level (20 ppb) for AFB in the feed for dairy cows and the 0.5 ppb for AFM in milk. Studies have revealed that approximately 1% of the AFB in the feed consumed by dairy cows is converted to AFM in them milk. Using a 1% conversion it can be seen that a cow which consumes 50 ppb AFB over all in her feed will produce approximately 0.5ppb AFM in her milk. Therefore, if a cow consumes 20 ppb AFB, (the action level for dairy cow feed) then only approximately 0.2 ppb AFM will be found in her milk, a concentration considerably lower than FDA action level of 0.5 ppb. Dr. Draughon observes: Since the FDA Action Levels for aflatoxin B1 in other human foods is 20 ppb, some scientists consider the cow as a filter for removing 99% of the more hazardous afla-toxin B1 from corn and other cereals and therefore milk is considered to be a much safer product than grains and oilseeds (Bo-dine and Mertens, 1989). The very conservative level of 0.5 ppb aflatoxin Ml in milk was established because (1) milk can constitute the major nutrient of the rapidly growing young, (2) the rapidly growing young are theoretically at the most vulnerable stage of induction of carcinogenesis and (3) in the absence of firm knowledge on the degree of risk, exposure to “unavoidable” carcinogens should be kept to the lowest level practically achievable (Sto-loff, 1980). Id. at 9. In establishing regulatory “action levels,” responsible governmental agencies attempt to determine the level in the diet (of the substance under investigation) below which it would only constitute a “negligible risk.” According to Dr. Draughon: The term “negligible risk” is defined by FDA as one excess cancer above background per million persons exposed using conservative (the highest possible) risk assessment model (Winter and Francis, 1997). When regulatory levels of natural toxins are established in foods, these are termed “Action Levels” rather than safe levels or other nomenclature. It should be pointed out that the FDA is not bound to prosecute by these action levels and that exemptions can and have been made when necessary under emergency circumstances. Action levels may be raised or lowered as deemed appropriate by the FDA depending on environmental conditions. Id. 8. Plaintiffs expert Dr. Teitelbaum has served on an OSHA advisory panel. His testimony tends to confirm Dr. Draughon’s analysis of regulatory action levels. See his testimony in Volume 2, Daubert hearing, pp. 42-48. The greatest aflatoxin production occurs in those years which combine serious droughts followed by very rainy harvest seasons. Historically, three of the worst years, since records have been maintained, were 1977, 1978 and 1980. Dr. Draughon notes the many food products in which aflatoxins are found: Aflatoxins are found in numerous food products such as milk and dairy products (Blanco et al., 1989, Galvano et al, 1996); corn and other cereals (Shotwell, et al, 1973); peanuts, tree nuts, cottonseed and other oil seeds, Brazil nuts, coffee beans, pistachio, sunflower seeds and numerous tree nuts and animal feeds (Gelda and Luyt, 1977); health foods (Mislivic et al., 1979);. Aflatoxins can also be produced on cheese, fermented meats, and numerous other food products such as coffee, spices, etc. (Draughon, 1979). Aflatoxins have also been found in paprika, nutmeg, pistachio, cayenne pepper, chili powder, black pepper, sorghum, cassava, wheat, barley and tissues of pigs, beef cattle and poultry (Nakazato, et al., 1991). Aflatoxin are highly stable to heat and are not removed by cooking the food. Id. at 8. When one checks to determine the effect of AFB on humans it is natural to study its effect on those persons who work in a situation in which they are continuously, or often, exposed to airborne dusts containing such aflatoxin. Dr. Draughon states in her report: Agricultural workers may be exposed to aflatoxin contaminated spores in the transferring, harvesting, grinding, feeding and handling of contaminated corn or other grains or oilseeds. The effects on agricultural workers in the United States are not known, however, a number of small epidemiological studies in other countries (Hayes et al, 1984) have shown that breathing mold dust during grain or peanut handling is potentially a problem and that it deserves further investigation in the United States. * * * * * * Studies have been conducted on airborne dust generated from corn contaminated with A. flavus in the United States and several epidemiology studies in the Netherlands have shown a potential hazard of increased liver cancer after inhalation of aflatoxin B1 contaminated dusts (Hayes et al, 1984). Airborne levels of aflatoxin B1 in 1980 (one of the high aflatoxin years) in a grinding and feeding operation in the United States ranged from 1,200 to 43,200 ng/g or 183 to 1760 ng aflatoxin B1 per cubic meter of air (Drake et al, 1976). An excellent study by Hill et al. (1984) on viable fungi (mold) in dust showed that over 90% of the aflatoxin B1 detected in dusty air at a grain elevator was in the fraction containing conidia (spores) and live fungi. Caution must be used in trying to compare respiratory exposure of workers in a dirty dusty environment such as feedmill where aflatoxin B1 is present in the air primarily in mold spores and mycelia at levels as high as 42,000 ppb to a dairy plant environment where the only source of aflatoxin is as a chemical metabolite (aflatoxin Ml) found at low levels (generally 0.05ppb) in the milk. Not only are the two chemicals (aflatoxin B1 and Ml) very different, but the levels of exposure and potential carcinogenicity are extraordinarily different (Stoloff, 1980) Id. at 11. The highest levels of aflatoxin B-l have been found in peanuts, cottonseed and corn. According to Dr. Draughon, “these levels may range as high as 740,000 ppb Aflatoxin B-l in one peanut and 207,000 ppb Aflatoxin in B-l in a small kernel of corn.... A study of peanut butter from 1982-1989 revealed that 9.8% of 2510 market basket samples exceeded the FDA Action Level of 20ppb. Of these 8.6% were between 20 and 50ppb, 3.7% were between 50 and 100 ppb, and 2.2% were above 100 ppb.” Id. at 12. This background information has not been challenged. What evidence exists that AFB is a human carcinogen? To answer this question Dr. Draughon reviews studies conducted on a variety of animals. The Court sets out her review in considerable detail: Aflatoxin Bl has been tested on almost all domestic animals, trout and common and uncommon laboratory animals including rhesus monkeys (Adamson et al, 1973). Even the lowly cockroach has not been spared (they are resistant). The common target organ of all species has been repeatedly shown to be the liver and bile duct (Van Rensburg et al, 1985; Wang et al, 1996; Zarba et al, 1992; Linsell, 1977). Since the majority of the metabolized Afla-toxin Bl (in the form of aflatoxin PI, Q1 and Ml) (Cast 1989) is excreted through the kidney (as urine) and through the colon (as feces), it is not surprising that aflatoxin Bl has also been shown to cause toxicity or carcinogenicity to the colon and kidney. :*c sfc íj: ;¡s Kidney and colon tumors have been reported along with liver tumors in animals given high levels of aflatoxin Bl. ****** Work since [1980] then has confirmed that aflatoxin Bl is a potent liver carcinogen primarily due to the manner in which it is metabolized in the Ever to the epoxide form (Bujons et al, 1995, Busby and Wog-an, 1984). My own studies with Salmonella typhimurium in the Ames test system clearly showed the mutagenicity of aflatox-in Bl but only when a liver enzyme fraction was added to metabolize the aflatoxin to the epoxide or active form (Draughon, 1982). Without metabolism of aflatoxin Bl to the epoxide by the mixed function oxi-dase enzymes of the liver, aflatoxin Bl has little or no mutagenicity in “in vitro” studies. Levels of aflatoxin Bl in the diet of test animals are generally in the 0.25 to 2 mg/kg (ppm) range to induce liver carcinoma. However, trout are much more sensitive and pale livers and liver tumors have been seen at 15 ppb aflatoxin Bl in the diet (Busby and Wogan, 1980). The scientific literature clearly shows that aflatoxin Bl causes toxicity, mutagenicity and hepa-toearcinogenicity in a number of animal models and toxicity and mutagenicity in various cell culture lines (Feuell, 1966; Wogan, 2967; Adamson, 1973; Peers and Linsell, 1973; Shibahara, et al, 1995). Aflatoxin Bl has been shown to be a hepa-tocarcinogen in rats at levels of 70 ng per dose over a two week period (total dose 0.63 mg). The target organ has been clearly shown to be the liver where most of the metabolism of aflatoxin Bl takes place. Other changes seen in the liver of animals exposed to aflatoxin Bl include focal lipid, hyperplasia, transitional cells (preneopla-sic) and hepatocellular carcinoma (Wogan et al., 1971). Numerous epidemiological studies have been conducted in other countries on afla-toxin Bl contaminated foods and invariably the major target organ has been the liver (Dvorackova, 1977; Peers, 1977; Butler and Neal, 1977) Although a positive correlation has been seen between aflatoxin Bl exposure and liver cancer in African and Asian populations, there is no evidence that aflatoxins contribute similarly to liver cancer incidence in the United States (CAST, 1989). Unlike Africa and Asia the incidence of liver cancer in the United States is relatively low. Although people in the Southeastern United States tend to have a higher dietary consumption of afla-toxin Bl than the other parts of the United States (7 ppb vs. 3ppb), no correlation between the increased level of aflatoxin in their diet and liver cancer can be found (CAST, 1989). The CAST report emphasizes that our current system of aflatoxin monitoring and control must be maintained to assure that exposure to aflatoxin remains low in the United States. Levels of aflatoxin B1 consumed in various parts of Africa and Asia have shown a direct correlation between consumption of large amounts of aflatoxin B1 and liver cancer (CAST, 1989). The levels of afla-toxin consumed by humans in these studies are in the milligram quantities per kilogram of body weight. For example, in Kenya the daily dietary aflatoxin intake was 3 to 15 mg/kg of body weight. Since a kg is approximately 2 pounds, a 140 pound man would have consumed 70(kg) times the 3 to 15 mg/kg aflatoxin B1 daily or 210 to 1050 mg (210,000,000 to 1,050, 000,000 ng) aflatoxin B1 daily. These levels would have resulted in a liver cancer incidence of 1 to 16 per 100,000 population, respectively. In Swaziland, the highest consumption of aflatoxin B1 in food was 43 to 53 mg/kg daily which would translate to 3,010 to 3,910 mg (3,010,000,000 to 3,910,000,000 ng) aflatoxin B1 daily for a 140 pound man. At this level of consumption, the cancer incidence increased to 35 liver cancers per 100,000 population. (CAST, 1989). If we look at the epidemiological studies of various populations in Africa which show an increased level of liver cancer (not respiratory), the mam source of aflatoxin B1 was cassava and peanut butter which had 465.5ppb (100% of samples were positive) and 143.6 ppb (99% of samples were positive), respectively (Peers and Linsell, 1973; Linsell and Peers, 1977; Appleton, 1985; Doll, 1990). Other epidemiological studies have repeatedly shown that humans are susceptible to liver carcinoma from consumption of high levels of aflatoxin B1 contaminated food products from Africa and Asia (Campbell et al., 1970; Akintonwa, 1982). Thai and Indian children became ill after eating 2 to 6 mg (2,000,000 to 6,000,000 ng) of aflatoxin daily in their corn over a period of a month. They developed a toxic hepatitis. There was no respiratory or oral cancer reported in this study. In Mozambique and Tanzania, there is a direct correlation between the ingestion of aflatoxin B1 in the diet and liver cancer. There have been no epidemiological associations reported in the 35 year’s of study of aflatox-ins between aflatoxin B1 and Ml and laryngeal cancer. The target organ for these toxins has repeatedly been reported to be the liver and bile duct. Adamson et al (1973), fed a newborn rhesus monkey with 0.05 mg/day (50,000 ng/ day) three times a week for 5 months; at 5 months the amount was increased to 0.2 mg/kg (200,000 ng/daily) every other week, at 44 months of age the dose was increased again to 0.8 mg/kg three times weekly every other week. A total of 840 mg (840,-000,000 ng) of aflatoxin B1 was given to the monkey by the time it was 74 months old. The major site of activity of the aflatoxin was on the liver and bile ducts. No respiratory or oral cancer was observed. It should be noted that “mg” are 1,000,000 times more concentrated than the “ng” which we generally measure in milk. Reddy et al. (1976) produced liver tumors in 50% of 18 Tree Shrews, a small (95 to 140 g) nonhuman primate, by feeding 2 ppm. Aflatoxin B1 .in the diet for 74 weeks or more (estimated intake was 24 to 66 mg (24,000,000 to 66,000,000 ng)). No respiratory cancer or tracheal cancer was seen in this study and all cancers observed in the study were hepatocellular (liver) carcinoma. The target organ was the liver and bile ducts. Primates tend to be in the middle range of susceptibility to hepatocar-cinogenicity of aflatoxin B1 with trout being one of the most sensitive animals and sheep being one of the most resistant mammals (CAST, 1989). Id. at 13-15. Plaintiff recognizes that aflatoxin B-l has been found to cause liver cancer in humans. Dr. Draughon, see supra, notes that, “Although a positive correlation has been seen between aflatoxin B-l exposure and liver cancer in African and Asian populations, there is no evidence that aflatoxins contribute similarly to liver cancer incidence in the United States.” And she notes that in various parts of Africa and Asia there are very high levels of exposure to aflatoxin B-l. So do these same Asian and African populations have a higher incidence of laryngeal cancer? Dr. Draughon answers: “There have been no epidemiological associations reported in the 35 years of study of aflatoxins between afla-toxin B-l and M-l and laryngeal cancer. The target organ for these toxins has repeatedly been reported to be the liver and bile duct.” To the Court, the absence of studies showing a correlation between even dramatically high exposures to aflatoxin B-l and laryngeal cancer in the very populations which do show a high correlation between such exposure and liver cancer, is of some significance. Of course, many of the studies dealt with dietary intake of aflatoxins rather than exposure via inhalation. But the handling of agricultural products which are sources of aflatoxin B-l in these African and Asian areas would seemingly subject such populations to significant exposure to aflatox-ins in the dust. Regardless, for whatever reason or reasons, we do not have epidemiological support for the proposition that those exposed to aflatoxin B-l in them diet or by inhalation have a higher incidence of laryngeal cancer than those who are not so exposed. After dealing with AFB, Dr. Draughon turns her attention to a study of the scientific evidence relating to the carcinogenicity and mutagenicity of AFM with which we are dealing in this case and which has not been studied nearly as thoroughly as aflatoxin B-1. Nevertheless, many studies have been made and she reviews them in her report as follows: Only a few studies are available on the carcinogenicity of aflatoxin Ml in animals and these will be reviewed. The first study is by Grice et al. (1973). Aflatoxin Bl was fed to lactating or pregnant rats in a toxic meal containing 10 ppm (10,000 ppb) aflatoxin Bl. The diet was so toxic that animals died so the researchers diluted the toxic meal with wholesome meal by 50% and 25% so that animals would not die before the study was completed. At this level, there were still abortions and deaths in the animals. Researchers were able to show liver toxicity and liver cancer developed in the adults and in some of the progeny. The referenced study used a toxic meal containing 10 ppm (10,000 ppb aflatoxin Bl). (The action level for milk is 0.5 ppb aflatoxin Ml). Therefore, extremely high levels of aflatoxin Bl had to be fed the Rat Dams to bring about liver damage in offspring. It is notable in this study that even with the extremely high levels of aflatoxin Bl being fed to rats and the high levels of Ml which progeny received in the milk of the dams (approximately 100 ppb aflatoxin Ml) that liver/bile duct toxicity and liver cancer were the findings. Three of the animals had cancer which had spread from the liver to other body organs (metastasis) due to the high levels of toxin being fed. One study actually looked at the feeding of aflatoxin Ml to rats at levels of 0.5, 5.0 and 50 ppb aflatoxin Ml and 50 ppb aflatoxin Bl (Hsieh et al, 1984). No tumors were produced at 0.5 or 5.0 ppb aflatoxin Ml in the diet of the animals which fed for 21 months. No tumors were produced in the 50 ppb aflatoxin Ml treatment group until after the 19 months of treatment. In the 50 ppb aflatoxin Ml treated rats, two animals out of 18 animals developed tumors which were confirmed as hepatocellular carcinomas. Four animals receiving 50 ppb aflatoxin Ml were found to have neoplastic nodules. In the aflatoxin Bl treated animals, 19 of 20 animals had liver tumors. Control animals receiving no afla-toxin had one liver tumor. The authors (Hsieh et al., 1984) concluded that aflatoxin Ml is about 2 to 10% as hepatocarcinogenic as aflatoxin Bl. A follow-up to this study by the same researchers (Cullen et al., 1987) reported that four animals had pulmonary adenomas. Two lung adenomas occurred in the control group (no aflatoxin) and two in the the aflatoxin treated group. Numerous testicular neoplasms were found in controls (no aflatoxin) and other treatments. The authors reported that Male Fisher strain 344 rats have been reported to develop these neoplasms spontaneously and frequently. There were no tracheal or respiratory cancers reported when animals were exposed to 50 ppb aflatoxin Ml. One interesting finding was that three intestinal neoplasms were found in the afla-toxin treated animals. As mentioned previously, this is probably due to the fact that aflatoxin is excreted in large amounts in the urine and feces of animals (Appleb-aum et al, 1982). In fact, aflatoxin Ml has been shown to be toxic to the kidney of animals because of this route of excretion. To quote the authors of this study (Cullen et al., 1987) “In the United States, human exposure to aflatoxin Ml occurs by ingestion of milk and other dairy products. The average human ingestion of aflatoxin Ml based on contamination levels of milk has been estimated to be 0.11 ppb. This is below the levels which were carcinogenic in Male Fisher Rats in this study. Human susceptibility to aflatoxin B1 hepatocarci-nogenesis is believed to be lower than that of Fisher rats. This is based on the low susceptibility of primates to aflatoxin-in-duced carcinogenesis and the similarity of aflatoxin B metabolism by postmitochon-drial fractions of human and monkey liver compared to the Fisher rat. Since aflatox-in M is considerably less potent than afla-toxin B, the risk of hepatocellular carcinoma induced by aflatoxin M appears to be low.” It is very important not to confuse aflatox-in Ml with aflatoxin B1 because of differences in their mutagenicity and carcinogenicity. While the mechanism of action of these toxins may be the same, their mutagenicity and carcinogenicity are quite different as shown above. In a few animal studies done with aflatoxin Ml in rats, the target organ has been shown to be the liver with occasional kidney toxicity. There have been no studies on aflatoxin Ml with primates of any type but we would expect primates to be more resistant than rats to aflatoxin Ml as they are to aflatoxin B1 for reasons discussed above by Cullen et al. (1987). There have been no studies showing any association between aflatoxin Ml and pulmonary diseases or respiratory cancer. There have been no studies either epidemiological or otherwise showing carcinogenicity in humans consuming aflatoxin Ml. This is due to the fact that levels of afla-toxin Ml are much lower than aflatoxin B1 in the food supply and aflatoxin Ml is much less carcinogenic than aflatoxin B1 (Cullen et al, 1987; CAST, 1989).' Id. At 15-17. The plaintiff does not agree with Dr. Drau-ghon’s analysis of some of the studies, see infra, but the Court concludes after reviewing those studies that her analysis is correct. E. The No-Threshold. Theory Citing the Reference Manual on Scientific Evidence, Federal Judicial Center (1994), plaintiff contends there is no threshold for genotoxins, in that any one molecule of such a carcinogenic mutational agent can produce alterations in genetic material leading to cancer. Plaintiff argues that everyone agrees Mr. McDougal was exposed to some aflatox-in, and, thus, he contends it is not necessary to calculate the level of his exposure. The Court has reviewed the Reference Manual on Scientific Evidence and notes the section upon which plaintiff relies is entitled Reference Guide on Toxicology. That section begins by noting that toxicology “classically is known as the science of poisons.” Id. at 185. A more modern definition includes “the study of the adverse effects of chemical agents on biological systems.” Id. (quoting Louis J. Casarett, John Doull, Casarett and Doull’s Toxicology: The Basic Science of Poisons, 3 (4th ed.1991)). The Reference Manual notes that there are “three central tenets of toxicology: First, ‘the dose makes the poison’; this implies that all chemical agents are harmful — it is only a question of dose.... Second, many chemical agents produce a specific pattern of toxic effects that are used to establish disease causation. Third, the responses of laboratory animals are useful predictors of toxic responses in humans.” Id. (footnotes omitted). Specifically, this section addresses the no-threshold model and determination of cancer risk at page 189: Certain mutational events, such as those leading to cancer and some inherited disorders, are believed to occur without any threshold. In theory, the cancer-specific alteration in the genetic material of the cell can be produced by any one molecule of the mutational agent. The no threshold model led to the development of the one hit theory of cancer risk, in which each molecule of a chemical has some finite possibility of producing the mutation that leads to cancer. This risk is very small, since it is unlikely that any one molecule of a potentially cancer-causing agent will reach that one particular spot in a specific cell and result in the change that then eludes the body’s defenses and leads to a clinical case of cancer. However, the risk is not zero. The same model also can be used to predict the risk of inheritable mutational events. [Footnote 18 in original] The plaintiff also brings our attention to the Appleton article. The “no threshold” views expressed therein deal with the Hepatic Maeromolecular Binding of AFB in rats showing a linear dose-response curve even at very low exposures. The significance of this seems to be: liver cancer can be induced with low level exposure to AFB. This study was designed to investigate whether a low dose threshold could be observed for the covalent binding of aflatoxin to liver macromoleeules at very low AFB exposures. A secondary objective was to examine the effect of hepatic GSH depletion caused by DEM pretreatment on the dose response curve for aflatoxin maeromolecular binding. Within the dose levels of AFB used, the authors could find no evidence for a threshold for such covalent binding to macromolee-ules. But they caution: although covalent binding of aflatoxin to macromoleeules is thought to be the first step in the pat