MEMORANDUM ORDER1
COPENHAVER, District Judge.
This matter is before the court on the motion of defendant E.I. DuPont De Nemours and Company, Inc. ("DuPont") to exclude
I.
Minor plaintiff Andrew Bourne ("Bourne") by and through his parents, Christopher Bourne ("Mr.Bourne") and Maggie Bourne ("Mrs.Bourne"), all residents of Essex, England, filed this action in February of 1997 against DuPont alleging that Mrs. Bourne's exposure to the DuPont-manufactured agricultural fungicide Benlate, while pregnant with the plaintiff, caused plaintiff to be born with severe birth defects.
Mrs. Bourne contends that she purchased Benlate from a local nursery to use in her home garden in March of 1986. (Mrs. Bourne Dep. at 39-41.) The Benlate was packaged in small sachets roughly the size of an individual-serving sugar packet, with each sachet containing 2.25 grams of Benlate powder, approximately 53% of which was comprised of Benlate's active ingredient, the chemical benomyl. (Upstone Aff. at 5.) Also supplied with the Benlate were separate sachets containing 3.0 grams of a surfactant called "Activex." (Id.) According to the directions contained in the package of Benlate, each sachet of Benlate powder was to be mixed with a sachet of Activex along with one UK gallon of water, approximately 4.5 liters, before application on plants. (See copy of Benlate label, attached as Ex. C to Upstone Aff.)
Mrs. Bourne contends that she followed the instructions and mixed a sachet of the Benlate and a sachet of the Activex in a gallon of water. Mrs. Bourne says that she sprayed the entire gallon of the Benlate-Activex-water mixture (hereinafter "Benlate mixture") on her home garden every ten to twelve days from March through late June, 1986. (Mrs. Bourne Dep. 39, 45-47, 68.) She testified at deposition that she applied the Benlate mixture liberally to her beans, strawberries, and roses, using a watering can, and when the beans grew taller, using both a watering can and a hand sprayer. (Id. at 38-40, 43-46, 91.) She testified that it took her approximately 45 minutes to one hour to mix and apply the Benlate mixture to her plants. (Id. at 105.)
Mrs. Bourne wore no gloves or protective face covering while working with the Benlate. (Id. at 98-100.) She testified that some Benlate powder got on her hands when she prepared the Benlate mixture and that the Benlate mixture got on her hands and perhaps her legs as she mixed. (Id. at 84-85.) When applying the Benlate mixture to her plants, she testified that the solution would get on her hands, legs, feet, and possibly face. (Id. at 85, 92-94, 96-97, 109.) She would bathe every day or every other day. (Id. at 128.)
Mrs. Bourne became pregnant with the plaintiff on or about May 5, 1986. (Ravits
II.
In a toxic tort case, a plaintiff must generally establish both general and specific causation for his injuries. Bourne must establish that he, via his pregnant mother, was exposed to a human teratogen, both at a level and by a means capable of causing his birth defects. He must also establish that the exposure to the teratogen did, in fact, bring about his particular maladies. Drs. Howard and Tackett both opine that Mrs. Bourne was exposed to Benlate, which they contend to be a human teratogen, at a critical stage in her son's fetal development, with the Benlate being absorbed into her blood stream at a level capable of causing Bourne's defects. They rule out genetic causes for Bourne's birth defects, and each opines that Mrs. Bourne's Benlate exposure is more likely than not the cause of her son's anophthalmia. In their reports, neither Dr. Howard nor Dr. Tackett refers to the cause of the plaintiff's birth defects other than the anophthalmia.
Dr. Howard is the senior lecturer at the University of Liverpool in the Faculty of Medicine. He is a licensed medical practitioner and a fetal toxio-pathologist. According to his report, in reaching his conclusions, Dr. Howard relied upon various studies and reports involving Benlate, the deposition transcripts of the Bournes, reports of plaintiff's expert witnesses and plaintiff's physicians, the existing epidemiology studies
Dr. Tackett is a pharmacologist and a professor of pharmacology and Toxicology at the University of Georgia. Dr. Tackett reached the same conclusion as Dr. Howard with respect to the causation of Bourne's anophthalmia. His opinion is based upon "(1) the known pharmacological/toxicological actions of Benlate which have been demonstrated to produce anophthalmia; (2) exposure to Benlate at a critical time in Mrs. Bourne's pregnancy; and (3) the fact that dermal absorption of Benlate results in systematic levels of benomyl and its metabolites in humans." (Tackett report at 1.)
A. Mrs. Bourne's exposure to Benlate
Dr. Howard estimated the amount of Benlate to which Mrs. Bourne was dermally exposed, and Dr. Tackett adopted the estimate. Based upon Mrs. Bourne's deposition transcript, Dr. Howard opined that 30% of Mrs. Bourne's skin was exposed to 5% of the gallon of Benlate mixture each time she applied the Benlate to her plants every 10 to 12 days. The 5% figure, Dr. Howard testified, represents "how much liquid ... [is necessary] to achieve the level of wetness which [Mrs. Bourne] described in her deposition." (Howard Dep. at 255.)
The 5% of a gallon, which is 225 milliliters,
Dr. Howard admits that these figures are not measured values, but are estimates based upon Mrs. Bourne's deposition testimony. (Id. at 333-334.) Dr. Howard conducted no testing or measurements to arrive at his figures. (Id. at 255, 295, 331-34, 670-71.) He is unsure how much, if any, of the purported 50 microliters per square centimeter of the Benlate mixture either ran off of Mrs. Bourne's skin or was rubbed off onto her clothing. (Id. at 337-38.) He did not address a published study conducted by DuPont examining dermal exposure to Benlate in a home garden setting which concluded that dermal exposure to benomyl using two gallons of Benlate containing approximately 9.5 grams of benomyl in a compression sprayer was less than 1 milligram of benomyl. See Leighton P. Everhart & Richard F. Holt, Potential Benlate Fungicide Exposure During Mixer' Loader Operations, Crop Harvest, and Home Use, 30 J. Agric. Food Chem. 222 (1982)("DuPont Everhart study"). Converting 1 milligrams to 1,000 micrograms and dividing by 4,500, the number of square centimeters of Mrs. Bourne's body Dr. Howard contends was exposed to the Benlate mixture, then dividing by 2 to account for the study's use of 2 gallons, one is left with a figure of .11 micrograms per square centimeter. Dr. Howard's estimate of 12.5 micrograms per square centimeter exceeds this figure by about 113 times. (Howard Dep. at 333.) Nor did he address a study conducted by the National Institute for Occupational Safety and Health ("NIOSH") which found that nursery workers engaged in weighing, mixing, and applying Benlate with compression sprayers are exposed to between .14 and
B. Dermal Absorption
The estimate of the dermal transmission rate of benomyl into human blood varies based upon the source. DuPont's expert, Dr. Howard I. Maibach, opines that the human dermal absorption rate for benomyl is less than 1%, whereas the United States Environmental Protection Agency ("EPA") has adopted a 3.5% dermal transmission rate and the California EPA refers to a 10% dermal transmission rate.
The dermal absorption rates of both the EPA and the California EPA are based upon rat studies. The EPA's figure is based upon a study conducted in 1978-79 by Belasco involving the dermal absorption of benomyl on rat skin. In this study, the dermal absorption rate was 3.5% after 10 hours at a .1 milligram dose, but with lower absorption rates for lesser time intervals.
Based upon his estimation that Mrs. Bourne was dermally exposed to 56.25 milligrams of Benlate with each use, Dr. Howard calculated Mrs. Bourne's total amount of benomyl absorption using several different dermal absorption rates.
Plaintiff nevertheless asserts that in addition to the California EPA rat dermal absorption study finding a 10% dermal absorption, a study conducted for plaintiffs by TNO ("TNO study") in the Netherlands and led by W. Mueling, involving human dermal absorption of benomyl, provides "compelling evidence" of a dermal transmission rate of at least 3.5%. (Pl.'s Resp. Motion to Exclude Howard and Tackett at 28.) Drs. Howard and Tackett address the TNO study generally in their reports to state that the study provides evidence that benomyl applied dermally becomes bioavailable.
The study was conducted in two phases. In the first phase, the samples were analyzed by high performance liquid chromatography ("HPLC") to detect and measure benomyl metabolites MBC, 5-HBC, and STB. (Mueling Dep. at 74-76.) MBC is the only benomyl metabolite that Drs. Howard and Tackett believe to be teratogenic. (Howard Dep. at 240, 401-02; Howard 10/04/01 Dep. at 97-98; Tackett Dep. at 59.) Specifically, 5-HCB is not claimed by Drs. Howard and Tackett to be teratogenic. (Id.)
No MBC or STB was detected in any blood sample and only 1 of 176 blood samples had a detectable, but non-quantifiable, level (i.e., a trace) of 5-HBC. (TNO study at 3.) 5-HBC was detected and measured in the urine samples. (Id.) In the second phase of the test, half of the blood and urine samples were re-analysed using a more sensitive detection method called liquid chromatography-tandem mass spectrometry. (Mueling Dep. at 74-76.) MBC was detected in some plasma samples but not at quantifiable levels. (Id.) Again there were detectable amounts of the benomyl metabolite 5-HBC found in the urine excreted for up to 72 hours following exposure.
However, the highest levels of MBC detection were found in blood plasma samples taken prior to benomyl administration, and urine samples from four of the testing subjects tested positive for 5-HBC prior to any benomyl administration. (TNO study, Appendix 3) Mueling "speculate[s]" that the pre-dose benomyl metabolite detection could be the result of food ingested by the test subjects prior to the commencement of the study. (Mueling Dep. at 59-60.) Mueling testified that he only subtracted pre-exposure amounts of 5-HBC found in the urine and MBC found in plasma from the amounts of these metabolites
Mueling testified that no conclusions could be drawn from the second portion of the study and that other than listing those results in the TNO study report, he did not use the results for any other purpose. (Id. at 75-77.) The first portion of the study found "the plasma levels did not reach the limit of detection [and] [w]hat cannot, therefore, be determined from this investigation is the degree of skin exposure at which plasma levels of benomyl would have become detectable, which (naturally) would occur when the clearance rate of the liver was being exceeded." (TNO study at 24.)
It is the presence of the 5-HBC metabolite in the test subjects' urine samples which Drs. Howard and Tackett contend support their 3.5% dermal absorption rates for Benlate on human skin. Dr. Howard contends that the 5-HBC evidences the amount of benomyl that had at one time been absorbed through the skin of the test subjects before being excreted in their urine. (Howard 10/04/01 Dep. 53-64.) Despite the fact that no quantifiable MBC was found in the plasma of the test subjects, Dr. Howard, using the respective molecular weights of 5-HBC and the benomyl metabolite MBC, took the measured amounts of 5-HBC present in the test subject's urine to calculate what he contends is the amount of benomyl that was absorbed through their skin to become bioavailable in the form of MBC in their blood. (Howard 10/04/01 Dep. at 61.) While his specific mathematical computations of the back-calculation of 5-HBC to MBC
C. Teratogenicity
In addition to concluding that Mrs. Bourne was exposed to benomyl which was absorbed into her body through her skin, Drs. Howard and Tackett opine that benomyl is a human teratogen, capable of causing the plaintiff's anophthalmia. They rely upon in vivo
Drs. Howard and Tackett cite to another rat gavage study conducted by a professor at the University of California in 1991 which revealed ocular abnormalities in 43% of rat offspring at a dose level of 62.4 milligrams per kilogram of weight. E. Hoogenboom, Effects on the Fetal Rat Eye of Maternal Benomyl Exposure, 10 Current Eye Research 7, 601-612 (1991) (Ex. 12, Def.'s Mot. Exclude.) Another rat gavage study performed by Culick in 1981 wherein 125 milligrams per kilogram per day of benomyl were injected into pregnant rats revealed teratogenic effects. Robert Culick, Determination of Benomyl/Methyl-2-Benzimidazole Carbamate (MBC), 4-OH MBC and 4-OH MBC Concentration in Maternal Blood and in the Concepti of Rats Exposed to Benomyl by Gavage, Haskell Report No. 970-80. Finally, a whole body autoradiography study ("Covance study"), sponsored by DuPont, revealed a concentration of benomyl in the uveal tract, the area lining the inside of the eye behind the cornea. Whitby, C-Benomyl: Quantitative Whole Body Autoradiography Following Oral Administration (2mg/kg) to Female Pigmented Rats, Covance Laboratories (1998) (Ex. 49, Def.'s Mot. Exclude.)
In addition to using in vivo rat studies to support their contention that benomyl is a human teratogen, Drs. Howard and Tackett also used in vitro tests. Dr. Howard relies upon in vitro tests conducted by Dr. Dick Van Velzen and Dr. Graham McLean. Dr. Tackett relied only on the in vitro study of Dr. McLean. Dr. Van Velzen, in studies performed in 1996 and 1997, dosed human fetal lung cells, fibroblasts, in varying concentrations of Benlate for a period of 24 hours. He then examined the cells to ascertain the smallest amount of Benlate concentration at which there was any observable effect on the cell through micronuclei
Dr. McLean, in a similar in vitro study conducted in 1997, exposed human cancer nerve cells, neuroblastomas, and rat cells, to benomyl of varying concentrations for 24 hours. (McLean Dep. at 77-78.) He reported a LOEL for the rat cells at 3 parts per billion benomyl. McLean, et al., The Effect of Benomyl on Neurite Outgrowth in Mouse NB2A and Human SHSY5Y Neuroblastoma Cells In Vitro, NeuroToxicology 19(4-5):629-631 (1998).
Based upon these in vitro and in vivo tests, Drs. Howard and Tackett inferred that benomyl is a human teratogen and extrapolated the human threshold dose for teratogenicity.
D. Epidemiology
In reaching their opinions with respect to causation, Drs. Howard and Tackett considered three epidemiological studies relating to pesticide exposure and birth defects, but rejected those studies as irrelevant and unreliable, based upon the opinions of plaintiff's expert epidemiologist, Dr. David Ozonoff.
1. Spagnolo study
A 1994 study by A. Spagnolo was conducted "following the report of clusters of anophthalmia and microphthalmia in England and Wales and their possible relation to the pesticide Benomyl." See A. Spagnolo, et al., Anophthalmia and Benomyl in Italy: A Multicenter Study Based on 940,-615 Newborns, Repro. Toxicology 8:397-403, 397 (1994). In this two-part study, the authors utilized registries of birth defects to identify 111 children with anophthalmia and microphthalmia born in Italy between 1986 and 1990, of a total of 940,615 births. After controlling for defects associated with chromosomal abnormalities, the authors divided Italy into regions and, in the first part or ecological portion of the study, examined the relationship between incidence of birth defects and use of benomyl by region. The results revealed a negative, nonsignificant coefficient, with there being a negative relationship between increased benomyl use by region and the incidence of anophthalmia and microphthalmia. Id. at 401.
In the second part or case control portion of the study, the authors examined the relationship between parental occupation and the incidence of children with eye defects by identifying children with anophthalmia and microphthalmia from the birth defect registries. The authors used the birth records to identify those children with parents who worked in the agricultural field. Of the 111 children with anophthalmia and microphthalmia as just noted, information on parental occupation was available in 90 of the 111 cases. Of those 90 cases, 4 had a parent with an agricultural occupation. Id. at 401-02. After excluding the defects associated with chromosomal abnormalities, there were 63 cases of anophthalmia and microphthalmia in which parental occupation information was available. Two of the children had a parent with an agricultural occupation. Id. at 402. The second phase of the study "did not show a significant association between agricultural occupation and anophthalmia and microphthalmia at birth." Id. at 402.
Dr. Ozonoff contends that the Spagnolo study is "incapable of providing information on the risks of anophthalmia/microphthalmia to the offspring of exposed pregnant women from Benlate exposure." (Ozonoff report at 5.) He maintains that the study does not examine the relationship between prevalence of exposure and prevalence of a health outcome inasmuch as the study does not measure individual exposure to benomyl, but instead compares disease prevalence with benomyl's use by region in Italy. (Id. at 6,8.) He contends that the results are "fundamentally uninterpretable in terms of the risks of Benlate to individuals."
In his evidentiary deposition, Dr. Ozonoff expounded on his report by stating that one who was employed as an agricultural worker in Italy during the relevant time period was not necessarily exposed to benomyl. (Ozonoff Dep. Dec. 17, 2001, Depo. at 154-56.) He testified that even assuming farm workers were exposed to benomyl, the subjects could have been all male or non-pregnant females, which would not have yielded useful results. (Id.) He also indicated that, while birth defect registries are mandatory, it is quite common that they aren't filled in, making it difficult to tell whether all the cases of a particular defect were properly recorded. (Id. at 150-51.) Upon cross-examination, Dr. Ozonoff testified that while not desirable, the use of exposure surrogates is common in epidemology. (Id. at 96-97.)
Dr. Ozonoff also testified that it would be "possible" but "extremely difficult" to design and conduct an epidemiology study to test the hypothesis of whether or not there is an association between benomyl exposure and anophthalmia. While he testified that he doesn't "know very much about ... the prevalence of Benlate exposure" in different populations, he stated that where the outcome, anophthalmia, is rare, and the exposure to benomyl is rare as well, "there is no real design you can use." (Ozonoff Dep. Dec. 17, 2001, at 129.) He refers to no studies or reports to support his opinion about the difficulty of designing such a study. Nor does he set parameters for what level of exposure and/or outcome would constitute "rare." He testified that if exposure to Benlate is not rare, then it would be possible to design a case control study examining the association between benomyl exposure and anophthalmia. (Id. at 130.)
2. Kristenson study
In a study published in 1997, the authors examined the relationship between the prevalence of birth defects as reported to the Medical Birth Registry of Norway from 1969 to 1989 out of a total of 192,417 births, and parental occupations in farming. The study found significant correlations between parental occupation in farming and several birth defects, but not eye malformations. P. Kristenson, et al., Birth Defects Among Offspring of Norwegian Farmers, Epidemiology 8:537-44 (1997). This 1997 published study does not mention benomyl but refers only to pesticides generally. However, in a letter to the editor of the British Medical Journal published in 1994, Kristenson offered an additional description of the same study and its results. The letter states in relevant part:
Kristenson, P. "Clusters of anophthalmia: No link with benomyl in Italy ... or in Norway." BMJ, 308: 206-207, 1994.
Dr. Ozonoff disregards the Kristenson study because the 1997 published study does not mention benomyl but refers only to pesticides generally. With respect to the letter to the editor by Kristenson which appears to further describe the results of his study as it related to benomyl, Dr. Ozonoff maintained simply that the study "is not informative as to the question of whether [bemomyl is] a risk factor." (Ozonoff Dep. Dec. 17, 2001, at 85.) In his report he also noted that the study might have erroneous results as a consequence of the failure to recognize less conspicuous forms of microphthalmia or cases in which microphthalmia is a concomitant malformation, and because the use of Benlate in Norway was very restricted during the relevant time. (Ozonoff Rep. at 11.) Neither his report nor his evidentiary deposition explain the basis for his statement that the use of Benlate in Norway was then very restricted.
3. Dolk study
A study examining geographical variation in anophthalmia and microphthalmia in England published in 1998 investigated the allegations of an English newspaper that there were "clusters" of blind children in England in farming areas associated with Benlate use. H. Dolk, et al., Geographical Variation in Anophthalmia and Microphthalmia in England, 1988-1994, British Medical Journal, 317:905-09. The study found that the overall prevalence of anophthalmia and microphthalmia in England was 1 in 10,000 births and found no statistically significant variation from region to region of England. Id. at 907.
Dr. Ozonoff does not discuss the Dolk study in his report except to state that "the existing data from England and Norway is similarly without relevance to this question [the risk of anophthalmia and microphthalmia to the offspring of exposed pregnant women to Benlate]."
Dr. Howard and Dr. Tackett both relied upon Dr. Ozonoff's opinions regarding the irrelevance of the epidemiological studies relating to Benlate use and anophthalmia and microphthalmia. (Howard report at 1.) Inasmuch, however, as Dr. Ozonoff acknowledged that the use of exposure surrogates, as in the Spagnolo study, is common in the field of epidemiology, and considering he provided only conclusory and speculative remarks about the Kristenson study and the Dolk study, it appears that the blanket rejection by Drs. Howard and Tackett of these epidemiological studies was unfounded. The court finds this particularly to be true when plaintiff had pointed to no epidemiological evidence supportive of his position.
III.
DuPont seeks to exclude the testimony of Drs. Howard and Tackett on several
In response, plaintiff asserts that, while each piece of data underlying the conclusions of Drs. Howard and Tackett may not be sufficient to independently justify the experts' conclusions, taken as a whole the body of data relied upon by Drs. Howard and Tackett support their conclusions, rendering their methodologies sound.
IV.
Effective December 1, 2000, Federal Rule of Evidence 702 was amended to reflect the United States Supreme Court's landmark decision of Daubert v. Merrell Dow Pharmaceuticals, Inc., 509 U.S. 579, 113 S.Ct. 2786, 125 L.Ed.2d 469 (1993). The revised Rule 702 states:
Fed.R.Evid. 702. As the Advisory Committee Notes indicate, the amendment to Rule 702 is consistent with the district court's "gatekeeping" function as articulated in Daubert. The proponent of the proposed expert testimony must establish its admissibility by a preponderance of proof. See Daubert, 509 U.S. at 592 n. 10, 113 S.Ct. 2786; Fed.R.Evid. 104(a).
In Daubert, the United States Supreme Court charged trial judges with the responsibility to act as "gatekeepers" to "ensure that any and all scientific testimony ... is not only relevant, but reliable." Daubert, 509 U.S. at 589, 113 S.Ct. 2786. As a part of its analysis, a trial court is to determine "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." Id. at 592, 113 S.Ct. 2786. It is for the trial court to make the "preliminary assessment of whether the reasoning or methodology underlying the testimony is scientifically valid and of whether that reasoning or methodology properly can be applied to the facts in issue." Id. at 592-93, 113 S.Ct. 2786. As to the first prong of the inquiry, whether the expert offers "scientific knowledge," the analysis focuses on whether the subject of the expert's testimony is grounded in the "methods and procedures of science," and constitutes "more than subjective belief or unsupported speculation." Id. at 590, 113 S.Ct. 2786. In order to qualify as "scientific knowledge," an inference or assertion must be derived by the "scientific method." Id. That is, the testimony must be supported
The Supreme Court in Daubert set forth a flexible, non-exhaustive checklist of four factors for trial courts to utilize in their evaluations of reliability. Id. at 593-94, 113 S.Ct. 2786. These factors include: (1) whether a theory or technique can be or has been tested; (2) whether it has been subjected to peer review and publication; (3) whether a technique has a high known or potential rate of error and whether there are standards controlling its operation; and (4) whether the theory or technique enjoys general acceptance within a relevant scientific community. Id. at 592-94, 113 S.Ct. 2786. In a later opinion, the Court further emphasized that these factors are flexible, not rigid, may or may not be pertinent in a given case and are to be applied based upon "the particular circumstances of the particular case at issue." Kumho Tire Co. v. Carmichael, 526 U.S. 137, 150, 119 S.Ct. 1167, 143 L.Ed.2d 238 (1999).
The second prong of the Daubert analysis focuses on whether the expert's testimony will be helpful to the trier of fact in deciding a fact in issue. Included in that analysis is the question of relevancy or "fit." Id. at 591, 113 S.Ct. 2786. The expert's proffered scientific testimony must be sufficiently tied to the facts of the case that it will be of assistance to the factfinder in resolving a disputed fact. Id. (citing United States v. Downing, 753 F.2d 1224, 1242 (3rd Cir.1985)). That is, there must be a "valid scientific connection to the pertinent inquiry" before the testimony is admissible. Id. at 591-92, 113 S.Ct. 2786.
The Court noted in Daubert that "vigorous cross examination, presentation of contrary evidence and careful instruction on the burden of proof are traditional and appropriate means of attacking shaky but admissible evidence." Daubert, 509 U.S. at 596, 113 S.Ct. 2786. However, when making the determination as to admissibility, a trial judge has considerable leeway in both the determination of reliability and the means the judge uses to make it. See Kumho Tire Co., 526 U.S. at 152, 119 S.Ct. 1167.
V.
The court does not propose to question the qualifications of Drs. Howard and Tackett for purposes of this order.
A. General Causation
Drs. Howard and Tackett have derived their general causation theory, that benomyl is teratogenic to humans, based solely upon in vivo rat gavage studies and in vitro tests. They discredit the only existing human data, consisting of epidemiological studies reflecting no statistical relationship between potential Benlate exposure
There can be no dispute that properly designed and conducted animal testing can yield relevant and useful information in the field of human toxicology. See, e.g., Turpin v. Merrell Dow Pharmaceuticals, Inc., 959 F.2d 1349, 1360-61 (6th Cir.1992), cert. denied, 506 U.S. 826, 113 S.Ct. 84, 121 L.Ed.2d 47 (1992) ("We do not mean to intimate that animal studies lack scientific merit or power when it comes to predicting outcomes in humans. Animal studies often comprise the backbone of evidence indicating biological hazards, and their legal value has been recognized by federal courts and agencies. Here, the record's explanation of the animal studies is simply inadequate.... The record fails to make clear why the varying doses of Bendectin or doxyalamine succinate given to the rats, rabbits and in vitro animal cells would permit a jury to conclude that Bendectin more probably than not causes limb defects in children born to mothers who ingested the drug at prescribed doses during pregnancy."). Likewise, in vitro tests provide useful information about metabolic processes at a cellular level, and may supplement existing animal and human data. See, e.g., Allen v. Pennsylvania Engineering, 102 F.3d 194, 198 (5th Cir.1996) (in vitro data shows only that ethylene oxide has mutagenic and genotoxic capabilities in living organisms, not that it necessarily causes brain cancer in humans). However, the extrapolations of Drs. Howard and Tackett, from highdosage, single species in vivo testing and lengthy benomyl exposure in vitro testing, to conclude that benomyl is a human teratogen and to establish the levels at which it is alleged to be teratogenic, are neither reliable, pursuant to the first prong of Daubert, nor relevant, under the second prong.
Courts considering the reliability of experts' extrapolation to human teratogenicity from in vivo and in vitro tests have recognized that such tests are generally considered to be suspect when relied upon for that purpose. In the absence of other strong indicators of the reliability of in vivo and in vitro tests, including supporting epidemiological studies, testing on closely related species,
The only existing epidemiological evidence
Moreover, the rat gavage studies and the in vitro tests relied upon by Drs. Howard and Tackett, using injections of high-levels of benomyl directly into the stomach of rats and high-level in vitro dosing of cells of both rats and humans in benomyl for 24 hours, do not "fit" with the facts of the case as alleged. General Elec. Co. v. Joiner, 522 U.S. 136, 118 S.Ct. 512, 139 L.Ed.2d 508 (1997), is germane. In Joiner, a city electrician who suffered from lung cancer filed suit against the manufacturer of polychlorinated biphenyls (PCBs) and manufacturers of electrical transformers and dielectric fluid, alleging strict liability, negligence, fraud, and battery. The district court excluded the testimony of electrician experts and granted defendants' motion for summary judgment. The United States Court of Appeals for the Eleventh Circuit reversed. The Supreme Court considered the fact that the plaintiff's proffered causation expert relied upon studies indicating that infant mice developed cancer of a different type than the plaintiff, after receiving massive gavage doses of PCBs. Id. at 144, 118 S.Ct. 512. The Court noted that the experts never explained "how and why [they] could have extrapolated their opinions from animal studies "far removed" from the circumstances of the plaintiff's exposure to PCBs." Id. Finding the studies upon which the experts relied to be "not sufficient, whether individually or in combination, to support their conclusions," the Court found that the district court had not abused its discretion in excluding their testimony. Id. at 146, 118 S.Ct. 512.
Similarly, the rat gavage testing relied upon by Drs. Howard and Tackett is "far removed" from the plaintiff's alleged exposure, with high doses of benomyl injected directly into the rats' stomachs. Using the Staples studies as an example, the lowest level of benomyl injection at which an ocular effect on offspring was noted was at 10 milligrams per kilogram of weight per day. A comparable dosage for Mrs. Bourne, who weighs approximately 50 kilograms, would be a direct injection (setting aside the fact that the chemical is alleged to have been absorbed dermally at a rate of 3.5%) of 500 milligrams, or one-half of one gram. Each sachet of Benlate contained approximately 1.19 grams of benomyl (based on 53% of the 2 .25 gram Benlate sachet). Thus, to be comparable to the lowest observable effect level, approximately one-half of the contents of a sachet would have to be injected into Mrs. Bourne. The other rat studies relied upon by Drs. Howard and Tackett involved far greater injections of benomyl.
The court concludes that the methodologies of Drs. Howard and Tackett in concluding that benomyl is a human teratogen are unsound.
B. Specific causation
Even assuming, arguendo, that the extrapolations from in vivo rat studies and in vitro studies to human teratogenicity levels were scientifically sound, the court nonetheless concludes that the opinions of Drs. Howard and Tackett relating to specific causation are not scientifically valid and reliable.
It appears that the conclusion of Dr. Howard, as adopted by Dr. Tackett, with respect to Mrs. Bourne's level of dermal exposure to Benlate, is highly speculative, without the indicia of reliability required by Rule 702 and Daubert. Rather than conducting any type of test or study to attempt to recreate the actions described by Mrs. Bourne in her deposition with respect to treating her plants with Benlate, it appears that Dr. Howard has developed arbitrary figures to represent what he deems to be the percentage of Mrs. Bourne's body exposed to Benlate and the amount of the Benlate mixture applied to her skin which he calculates to be 5% of the one-gallon Benlate mixture used periodically by her. While he contends on the one hand that the figure is based upon the portion of a gallon estimated by him as necessary to produce the level of wetness described by Mrs. Bourne, he also testified that he back-calculated the amount of dermal benomyl exposure necessary, using a 3.5% dermal absorption rate, to achieve a benomyl concentration of 20 parts per billion. (Howard Dep. at 117.) Thus, Dr. Howard's 5% figure is, at best, purely speculative and at worst, devised to ensure that a certain desired end—20 parts per billion—was met. In either case, the adopted methodology, or lack thereof, is contrary to principles of sound scientific method. See, e.g., General Elec. Co. v. Joiner, 522 U.S. 136, 146, 118 S.Ct. 512, 139 L.Ed.2d 508 (1997) ("nothing in either Daubert or the Federal Rules of Evidence requires a district court to admit opinion evidence that is connected to existing data only by the ipse dixit [an assertion made but not proved] of the expert"); Oglesby v. General Motors Corp., 190 F.3d 244, 250 (4th Cir.1999) ("A reliable expert opinion must be based on scientific, technical, or other specialized knowledge and not on belief or speculation, and inferences must be derived using scientific or other valid methods.").
Additionally, the 5% figure does not take into account pertinent published studies (DuPont Everhart study and NIOSH Hoekstra study, supra p. 8-9) examining the exposure of garden users to Benlate. See, e.g., Cooper v. Smith & Nephew, Inc., 259 F.3d 194, 203-04 (4th Cir.2001) (affirming trial court's exclusion of plaintiff's causation expert, in part, on basis that expert rejected, without offering sound explanation, medical literature and plaintiff's own medical records which tended to support another cause of plaintiff's condition). Nor is the 5% calculation capable of being tested or reproduced. Daubert v. Merrell Dow Pharmaceuticals, Inc., 509 U.S. 579, 592-94, 113 S.Ct. 2786, 125 L.Ed.2d 469 (1993)(setting forth non-exhaustive list of factors pertinent to whether an opinion is
The methodology utilized by Drs. Howard and Tackett in deriving a level of human dermal absorption for benomyl likewise appears to be unsound. In his report, Dr. Howard utilized several dermal absorption rates, the lowest thereof being 2%. He identifies several sources for the dermal absorption rates, including the EPA's use of a 3.5% rate and the amount of Benlate "potentially absorbed" by the test subjects in the TNO studies. The EPA's use of a 3.5% figure is based upon a 1979 study on the dermal absorption of Benlate on rat skin wherein 3.5% was absorbed after a period of 10 hours. See supra p. 9. Setting aside the fact that it is not alleged that Mrs. Bourne was exposed to Benlate for a 10 hour period, it is well established among the scientific community that rat skin is more permeable than human skin. (See Maibach Aff. at ¶ 48; Tackett Dep. at 126-27.) Dr. Tackett testified in his deposition that he believes that rabbit skin and rat skin are approximately 10 times more permeable than human skin with respect to Benlate or benomyl. While his report does not identify a specific rate which he has adopted, it mentions the EPA's 3.5% dermal absorption rate, based on rat studies, and formulated for risk assessment, not causation, purposes. (Tackett Report at 4.) The only study relied upon by Drs. Howard and Tackett relating to the dermal absorption of benomyl on living human skin is the TNO study conducted by Mueling.
Despite the seeming lack of useful results produced by the TNO study,
It appears that the back-calculation of 5-HBC to benomyl is internally inconsistent with the very TNO study upon which Drs. Howard and Tackett purport to rely. The conductor of the study, Mueling, testified at deposition that one cannot ascertain the amount of MBC or 5-HBC in the blood based on the TNO urine data. (Mueling Dep. at 107-08.) Mueling also testified that his TNO study did not reveal a rate of transmission through human skin. (Id. at 76-78.) The court concludes that the calculations of Dr. Howard, adopted by Dr. Tackett, purporting to reflect the rate of human dermal absorption of benomyl into the blood based upon the amount of 5-HBC found in the urine of the TNO test subjects constitutes merely the "ipse dixit" of Drs. Howard and Tackett and is not grounded in "the methods or procedure of science." See General Elec. v. Joiner, 522 U.S. at 146, 118 S.Ct. 512.
Whether derived from the molecular weight of irrelevant 5-HBC metabolites in TNO test subjects' urine or extrapolated directly from the 20-year old Belasco tests involving the administration of benomyl to permeable rat skin for extended durations, the 3.5% dermal absorption rate used by Drs. Howard and Tackett cannot be said to be methodologically sound.
VI.
It appearing that the opinions proffered by Drs. Howard and Tackett meet neither the requisite standards of reliability or relevance under Federal Rule of Evidence 702, as set forth by the United States Supreme Court in Daubert v. Merrell Dow Pharmaceuticals, Inc., 509 U.S. 579, 113 S.Ct. 2786, 125 L.Ed.2d 469 (1993) and its progeny, the court concludes that their testimony must be excluded.
Wherefore, for the foregoing reasons, it is ORDERED that DuPont's motion to exclude the testimony of Dr. Howard and Dr. Tackett be, and it hereby is, granted.
The Clerk is directed to forward copies of this order to all counsel of record and to post this published opinion at http://www.wvds.uscourts.gov.
FootNotes
Turpin, 959 F.2d at 1359 (quoting James Wilson, Current Status of Teratology, in Handbook of Teratology 60 (J. Wilson & C. Fraser, eds.1977)).
Dr. Tackett acknowledged at deposition that one species of animals will generally have a different teratogenic response to a chemical than will another animal species. (Tackett Dep. at 224.) Dr. Howard testified, "[i]t's usually said that to define something as a human teratogen it's desirable to have two animal models." (Howard Dep. at 672.)
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