UNITED STATES DISTRICT COURT
FOR THE DISTRICT OF COLUMBIA

___________________________________

Civil Action No. 99-1170 (EGS)

JIM J. TOZZI, et al.,

Plaintiffs,

v.

UNITED STATES DEPARTMENT OF HEALTH & HUMAN SERVICES, et al.,

Defendants.

___________________________________

DEFENDANT’S MEMORANDUM IN OPPOSITION TO
PLAINTIFF’S MOTION FOR PRELIMINARY INJUNCTION

Plaintiffs¹ have applied for a preliminary injunction in this action seeking an Order from this Court that would enjoin the defendants² from including any listing in the Biennial Report on Carcinogens ("RoC"), "that identifies the chemical tetrachlorodibenzo-p-dioxin ("dioxin" or "TCDD") as a ‘known human carcinogen’ or ‘known to be carcinogenic to humans,.’" See Plaintiffs’ Proposed Order.

Plaintiffs’ have failed to satisfy the requirements for a preliminary injunction and their motion should be denied. Plaintiffs do not and cannot show any likelihood of success on the merits of their claims. The merits of their claim are premised on the striking notion that the defendants do not understand, or know how to apply, their own listing criteria.³ Moreover, plaintiffs’ claimed economic injury is completely speculative and does not in any way amount to "irreparable injury." Finally, a balancing of the interests regarding the issuance of an injunction weighs in defendants’ favor, and the public interest also weighs against issuing an injunction.

Section 301(b) (4) of the Public Health Service Act, 42 U.S.C. § 241(b) (4), as amended, provides in pertinent part, that:

[t]he Secretary shall publish a biennial report which contains -

(A) a list of all substances (i) which either are known to be carcinogens or may reasonably be anticipated to be carcinogens and (ii) to which a significant number of persons residing in the United States are exposed;

(B) information concerning the nature of such exposure and the estimated number of persons exposed to such substances;

(C) a statement identifying (i) each substance contained in the list under subparagraph (A) for which no effluent, ambient, or exposure standard has been established by a Federal agency, and (ii) for each effluent, ambient, or exposure standard established by a Federal agency with respect to a substance contained in the list under subparagraph (A), the extent to which, on the basis of available medical, scientific, or other data, such standard, and the implementation of such standard by the agency, decreases the risk to public health from exposure to the substance . . .

This statutory requirement for a RoC was enacted in 1978 by Public Law 95-622, 92 Stat. 3412, 3435-36. The statute was amended in 1993 by section 2009 of Public Law 103-43, 107 Stat. 122, 213 to provide for a biennial rather than an annual RoC.

The RoC’s enabling statute does not provide criteria for listing a substance as a known human carcinogen or as reasonably anticipated to be a human carcinogen or as reasonably anticipated to be a human carcinogen. As a result, defendants themselves have promulgated and published their own listing criteria, first doing so in December, 1982. In September, 1996, after a thorough scientific review and public comment procedure, the listing criteria were revised to permit, among other things, consideration of so-called "mechanistic data" as part of the listing evaluation. See 61 Fed. Reg. 50499.

The adopted, revised criteria are as follows:

Known To Be A Human Carcinogen

There is sufficient evidence of carcinogenicity from studies in humans which indicates a causal relationship between exposure to the agent, substance or mixture and human cancer.

Reasonably Anticipated To Be A Human Carcinogen

There is limited evidence of carcinogenicity from studies in humans, which indicates that causal interpretation is credible, but that alternative explanations, such as chance, bias or confounding factors, could not adequately be excluded, or;

There is sufficient evidence of carcinogenicity from studies in experimental animals which indicates there is an increased incidence of malignant and/or a combination of malignant and benign tumors: (1) in multiple species or at multiple tissue sites, or (2) by multiple routes of exposure, or (3) to an unusual degree with regard to incidence, site or type of tumor, or age at onset; or

There is less than sufficient evidence of carcinogenicity in humans or laboratory animals,

however; the agent, substance or mixture belongs to a well defined, structurally-related class of substances whose members are listed in a previous Annual or Biennial Report on Carcinogens as either a known to be human carcinogen, or reasonably anticipated to be human carcinogen or there is convincing relevant information that the agent acts through mechanisms indicating it would likely cause cancer in humans.

Conclusions regarding carcinogenicity in humans or experimental animals are based on scientific judgment, with consideration given to all relevant information. Relevant information includes, but is not limited to dose response, route of exposure, chemical structure, metabolism, pharmacokinetics, sensitive sub populations [sic], genetic effects, or other data relating to mechanism of action or factors that may be unique to a given substance. For example, there may be substances for which there is evidence of carcinogenicity in laboratory animals but there are compelling data indicating that the agent acts through mechanisms which do not operate in humans and would therefore not reasonably be anticipated to cause cancer in humans.

This lawsuit and the instant application for preliminary injunction both concern the defendants’ interpretation of the revised listing criteria above. Plaintiffs claim that the listing criteria for the "Known To Be A Human Carcinogen" category does not permit use of so-called "mechanism of action data," also known as "mechanistic data," and that such data cannot be used to support a finding that there is "sufficient evidence of carcinogenicity from studies in humans" when the more traditional evidence from human epidemiological studies is less than sufficient.⁴

As explained below, plaintiffs’ interpretation of defendants’ listing criteria is simply mistaken. The final explanatory paragraph of the revised criteria, which was newly added on 1996, explicitly permits consideration of, which was newly added in 1996, explicitly permits consideration of, in reaching conclusions regarding carcinogenicity in humans or experimental animals, "data relating to mechanism of action," and consideration of such data is appropriate for both the "Known" and the "Reasonably Anticipated" categories. Moreover, because the revised criteria also explicitly state that a scientific conclusion regarding "carcinogenicity in humans" may be based on "all relevant information," it is clear that a substance may be listed in the "Known" category based on a sufficient combination of epidemiological studies and human mechanistic data.

III. The Proposed Listing Of Dioxin.

Dioxin is not commercially produced except as a research chemical at this time. It has been detected in commercial samples of some herbicides. It is also produced by paper and pulp bleaching, by incineration of municipal, toxic and hospital wastes, transformer fires and smelters. Draft Background Document, ("DBD"), at 1-1 to 2-2., Ex. 1. It is a very stable chemical compound, and it therefore remains in the atmosphere, soil, water and human tissue for long periods of time. Id. Currently, dioxin is predominantly spread via "atmospheric fallout" into soil and water, where it ultimately finds it way into most living creatures. Id. At 2-2. Ir is likely that every human has some level of dioxin in his or her body. See Attachment D8 to Plaintiffs’ Opposition to Defendants’ Motion to Dismiss.

Following the decision by the International Agency for Research on Cancer ("IARC") to upgrade its listing of dioxin to IARC’s highest category, "Group 1," (which listing indicates that "the agent is carcinogenic to humans;" Ex. 3, at 343), NTP proposed upgrading the dioxin listing in the RoC. Dioxin had previously been listed in the RoC as "reasonably anticipated to be human carcinogen." See 62 Fed. Reg. 37272-73. A notice announcing the intent to review dioxin for possible listing in the 9^th RoC as a "known human carcinogen" was published in the Federal Register on July 11, 1997. Id.

Final approval and publication of any listing in the RoC is preceded by a six step review process. As part of this review, two federal scientific review groups and one non-government scientific peer-review body (a subcommittee of the NTP Board of Scientific Counselors) evaluate the substances that are candidates for listing in the RoC. Each group reviews the available data according to the listing criteria above.⁵

Once a substance is nominated for an action, including an upgrade, a Draft Background Document" (DBD") is initially prepared for review and analysis by the various scientific review committees. Here, an initial DBD was circulated, first to the NIEHS/NTP Review Committee for the Report of Carcinogens, also known as "RG1." That Committee reviewed the proposal and recommended, on September 4, 1997, that the nomination be listed as a known human carcinogen. See 63 Fed. Reg. 68783-85.

The second review phase of the dioxin nomination was done by the NTP Executive Committee’s Interagency Working Group for the Report on Carcinogens, known as "RG2." On September 16, 1997, RG2 recommended the listing of dioxin as a known human carcinogen in the RoC. Thereafter, a September 30, 1997 draft background document for dioxin was prepared incorporating the changes and recommendations of RG1 and RG2. See generally, Ex. 1.

The September 30, 1997 DBD for dioxin outlines and summarizes the scientific findings that support the proposed dioxin listing. In summary, these findings indicate that dioxin is known to be a human carcinogen based on (1) Human studies that found "an association between dioxin exposure and cancer mortality with respect to all cancers combined, non-Hodgkin’s lymphomas, and lung cancer;" (2) "studies in experimental animals that have shown that TCDD induces benign and malignant neoplasms at multiple tissue sites in multiple species;" and (3) a "compelling body of evidence [that] indicates a basic similarity in the mechanism of induction of animal and human biochemical and toxicological responses to TCDD at comparable doses and tissue levels." See DBD, Ex. 1, at p. RC-1.

In explaining further the scientific support for the proposed listing, the DBD reviews the epidemiological studies and notes that in early 1997 the IARC monograph has determined that the epidemiological evidence was "limited" for the carcinogenicity of dioxin in humans. DBD, Ex. 1, at ¶ 3.0, p. 3-1. The DCD also noted that IARC had concluded that the epidemiological evidence overall showed that, "the strongest evidence of increased cancer mortality is for all cancers combined rather than for cancers of any particular sites." Id. at ¶ 3.0, p. 3-2,

In the summary section under the heading, "Other Information Relating To Carcinogenesis or Possible Mechanisms of Carcinogenesis," the DBD states that "[t]here is scientific consensus for a common mechanism of action of TCDD and other chlorinated dibenzodioxins, dibenzofurans, and planar PCBs. In humans and rodents, the mechanism involves initial binding to the aryl hydrocarbon (Ah) receptor. TCDD has the highest affinity of the chlorinared dioxins and furans for both rodent and humans [sic] forms of the Ah receptor." DBD, Ex. 1, at RC-2.

The DBD goes on to describe the meaning and importance of the scientific consensus relating to dioxin’s mechanism of action data. In the discussion section at paragraph 7.1, under the heading "Mechanism of Carcinogenicity", the DBD states that,

Studies indicate the Ah receptor activation is required for the carcinogenicity of [dioxin]." . . . The Ah receptor is a ubiquitous intracellular protein found in cells of vertebrates, including rodents and humans, that acts as a signal transducer and activator of gene transcription. TCDD induces a wide spectrum of biological responses, including induction of gene expression, altered metabolism, altered cell growth and differentiation, and disruption of steroid hormone and growth factor signal transduction pathways. Similar Ah receptor-mediated responses have been observed in both rodents and humans. There is scientific consensus that binding to the Ah receptor is a necessary step in the mechanism of elicitation of these responses and that this mechanism is conserved in humans and rodents. Similar responses observed in both humans and rodents occur at similar tissue concentrations of TCDD.

DBD, Ex. 1, ¶ 7.1, at p. 7.1 (emphasis added).

Thus, the DBD presents a clear picture of the scientific evidence in support of the proposed dioxin listing under the "Known To be A Human Carcinogen" category. First, the epidemiological evidence then available showed that industrial exposure to dioxin in the cohorts studied indicated an increased risk for cancer in general, rather than for any one particular type of cancer. DBD, Ex. 1, ¶3.0, p. 3-1, 3-2. The DBD clearly represented that this epidemiological evidence according to IARC was "limited." Id. at p. 3-1. The DBD shows, however, that there is "scientific consensus" relating to the mechanism of action data for dioxin. In particular, the mechanistic data studies indicate "that Ah receptor activation is required for the carcinogenicity of [dioxin]." Id. at p. 7-1. Mechanistic data also clearly shows that dioxin induces a wide spectrum of biological responses in both human and rodent cells, including cancer, by, as necessary step, binding to an intracellular protein known as an "Ah receptor." Id. at RC-2 and ¶ 7.1.

Another notice was published in the Federal Register soliciting final public comments on the nomination of dioxin. See 63 Fed. Reg. 13418.

Following comments by plaintiff Tozzi on the October, 1997 meetings, and his own review of the proceedings, Dr. Olden ordered a re-review of the dioxin listing by the Board RoC Subcommittee. See 63 Fed. Reg. 18435. The public comment period was extended until June 15, 1998, sand written statements were again requested in addition to oral presentations for the meeting of the NTP Board RoC Subcommittee on December 2 and 3, 1998. See 63 Fed. Reg. 18435 and 63 Fed. Reg. 57132-33. A supplement to the DBD for dioxin was prepared. See Ex. 2. On re-review, the NTP Board RoC Subcommittee voted against the upgrade by a vote of 5 yes, 7 no, and 1 abstention. See 63 Fed. Reg. 68783-85. NTP once again solicited final public comments on the nomination of dioxin on December 14, 1998. See 63 Fed. Reg. 68783-68785. The NTP Executive Committee subsequently voted on February 24, 1999, to affirmatively recommended listing dioxin as a known human carcinogen. See Lucier Declaration, Attachment 2 to Defendants’ Motion to Dismiss. The recommended dioxin listing is currently under consideration by Dr. Olden, the Director of NIEHS, prior to any final by the Secretary. ⁶

IV. ARGUMENT

Before addressing in detail the particular claims plaintiffs advance, it is necessary to review the legal standards this Court should apply. The criteria that govern the issuance of preliminary injunctive relief in the District of Columbia are well-settled. In order for the Court to exercise its power to grant this extraordinary relief, the plaintiff must show: (1) a strong likelihood of prevailing on the merits of its claim; (2) that without injunctive relief it will suffer irreparable harm; (3) that, balancing hardships, the issuance of an injunction will not substantially harm other interested parties; and (4) that the public interest favors the requested injunction. Wisconsin Gas Co. v. FERC, 758 F.2d 669, 674 (D.C. Cir. 1985); Virginia Petroleum Jobbers Ass’n v. FPC, 259 F.2d 921, 925 (D.C. Cir. 1958) (per curiam); Washington Metropolitan Area Transportation Comm’n v. Holiday Tours, Inc., 559 F.2d 841, 843-44 (D.C. Cir. 1977). A preliminary injunction is a drastic and extraordinary form of relief that should not be granted absent a clear and convincing showing by the moving party, Yakus v. United States, 321 U.S. 414 (1944); Kahane v. Secretary of State, 700 F.Supp. 1162, 1165 (D.D.C. 1988), and "[t]he injury must be both certain and great; it must be actual and not theoretical." Id,; Wisconsin Gas, 758 F.2d at 674. This is an exacting standard that, as we explain below, plaintiff has not met.

To obtain preliminary injunctive relief, plaintiffs have the heavy burden of demonstrating a strong likelihood of prevailing on the merits of its claim. This they cannot do. Indeed, as careful review of the administrative record shows that there is no merit to any of plaintiffs’ substantive claims.

Under the Administrative Procedure Act ("APA"), agency action will be upheld unless it is "arbitrary, capricious, an abuse of discretion, or otherwise not in accordance with law."

5 U.S.C. § 706(2) (A). The court will not "substitute its own judgment for that of the agency." Citizens to Preserve Overton Park, Inc. v. Volpe, 401 U.S. 402, 416 (1971); see also Troy Corp. v. Browner, 120 F.3d 277, 283 (D.C. Cir. 1997).

Plaintiffs’ arguments may be summarized as follows: First, plaintiffs argue that the defendants’ proposed dioxin listing is arbitrary and capricious because it is, they allege, contrary to the plain meaning of the agency’s own listing criteria, and is therefore based on irrelevant factors. See Memorandum In Support of Preliminary Injunction ("Memorandum"), pp. 12-21. Plaintiffs also allege that the proposed dioxin listing constitutes a substantial and unexplained departure from past agency practice, and is therefore arbitrary and capricious. See Memorandum, pp. 21-25. Finally, plaintiffs claim that the proposed listing is arbitrary and capricious because the defendants have allegedly in inaccurately described the scientific evidence upon which they rely and because that evidence allegedly does not support the proposed listing. See Memorandum, pp. 25-31. Plaintiff does not have a substantial likelihood, indeed, any likelihood of prevailing on the merits of these arguments.

Plaintiffs have cast the first argument mentioned above in terms of whether the agency relied on "relevant factors." For instance, plaintiffs argue that because the defendants considered mechanistic data in support of the proposed dioxin listing they relied n an irrelevant factor. Memorandum at 12-13, 21. Certainly as part of a Court’s review of agency action it may consider whether the agency relied on "relevant factors," and whether or not there was a "clear error of judgment." Troy, supra, 120 F.3d at 283; see also Motor Vehicles Mfrs. Ass’n v. State Farm Mutual Auto Ins. Co., 463 U.S. 29, 43 (1983); Nursing Center of Buckingham and Hampden, Inc. v. Shalala, 990 F.2d 645, 650 (D.C. Cir. 1993).

Plaintiffs argue that in relying on such irrelevant factors the defendants have acted contrary to the plain meaning of the "Known To Be A Human Carcinogen" listing criteria, because, according to plaintiffs, that criteria does not permit consideration of mechanistic data. Plaintiffs also argue that reliance on such irrelevant factors have caused defendants to disregard the listing requirement that there be "sufficient evidence" from "studies in humans" to support a "causal relationship" between exposure to the substance and human cancer. Memorandum at 16-21.

Plaintiffs’ first argument on what is or is not a "relevant factor" therefore turns on how the listing criteria is interpreted. If the "Known To Be A Human Carcinogen" listing criteria can rationally be interpreted to permit consideration mechanistic data to support a finding that there is "sufficient evidence of carcinogenicity from studies in humans which indicates a causal relationship between exposure to the agent, substance or mixture and human cancer," then the defendants’ actions are not contrary to the plain meaning of the criteria and they have not relied on irrelevant factors. In fact, as explained below, the defendants have always interpreted the 1996 listing criteria to permit consideration of mechanistic data in the "Known" category, and this interpretation is supported by the record.⁷

Similarly, plaintiffs’ second argument also turns on how the "Known" category listing is interpreted. Plaintiffs, however, frame this claim in terms of whether the defendants have deviated without sufficient explanation from past agency practices. It is, of course, well established that "an agency practices. It is, of course, well established that "an agency cannot depart from a long-standing policy without providing sufficient explanation of its rationale for altering course." DSE, Inc. v. United States, 169 F.3d 21, 31 (D.C. Cir. 1999); see also Pontchartrain Broadcasting Co., Inc. v. FCC, 15 F.3d 183, 185 (D.C. Cir. 1994); Graphic Communications Int. Union v. Salem-Gravure Division of World Color Press, Inc., 843 F.2d 1490, 1493 (D.C, Cir. 1988).

To show the alleged deviation from past practice, however, plaintiffs again assert that the 1996 listing criteria for the "Known To Be A Human Carcinogen" category does not permit consideration of mechanistic data. By asserting that the 1996 listing criteria revisions effected essentially no changes to the "Known" category, plaintiffs present the proposed dioxin listing as a rogue and unjustified aberration vis a vis all the "Known" category listings prior to 1996. Memorandum at 22-24.

The dioxin listing might well be a rogue aberration if plaintiffs’ interpretation of the listing criteria were correct. But if, as established below, the 1996 revisions were intended to and did permit consideration of mechanistic data as part of the "Known" category, then the defendants’ proposed dioxin listing is in accordance with existing policy and is not a departure at all,

Thus, plaintiffs’ second argument, like their first, boils down to an interpretation of the defendants’ listing criteria. The question is whether a finding of "sufficient evidence of carcinogenicity from studies in humans which indicates a causal relationship between exposure to the agent, substance or mixture and human cancer," may be based upon a combination of arguably less than "sufficient" evidence from human epidemiological studies in conjunction with strong human mechanistic data. The defendants interpret, and have always interpreted since 1996, their "Known" listing criteria to permit exactly that result, based on the changes to the listing criteria brought about by the final descriptive paragraph following the specific "Known" and "Reasonably Anticipated" categories, as explained below.

Before explicitly discussing the listing criteria, however, it is helpful to point out the applicable standard in this case by which the Court evaluates an agency’s interpretation of its own rules and regulations. As plaintiffs’ candidly agree, this standard of review applies to the listing criteria here, and it is particularly deferential. Memorandum at 14.

The Supreme Court has made it clear that a court reviews with "substantial deference" an agency’s interpretation of its own regulations. Thomas Jefferson University v. Shalala, 512 U.S. 504, 512 (1994); see also Martin v. Occupational Safety and Health Review Comm’n, 499 U.S. 144, 150-51 (1991). Indeed, the defendants’ interpretation of their own listing criteria here "is controlling unless it is plainly erroneous or inconsistent with the [criteria]." Wyoming Outdoor Council v. United States Forest Service, 165 F.3d 43, 52 (D.C. Cir. 1999) (internal quotations omitted and emphasis added); see also National Trust for Historic Preservation v. Dole, 828 F.2d 776, 782 (D.C. Cir. 1987). Here, where the agency itself has drafted the rule or regulation at issue, not only is the Court’s review deferential, it is "more deferential ... than that afforded under Chevron."⁸ National Medical Enter. v. Shalala, 43 F.3d 691, 697 (D.C. Cir. 1997). Indeed, the Supreme Court has made it clear that "broad deference is all the more warranted when . . . the regulation concerns ‘a complex and highly technical regulatory program.’" Thomas Jefferson, supra, 512 U.S. at 512. The scientific review of toxic substances is such a program. Cf. Troy, supra, 120 F.3d at 283 (the Court reviews scientific judgments of an agency "‘not as the chemist, biologist or statistician that [it is] qualified neither by training nor experience to be, but as a reviewing court exercising [its] narrowly defined duty of holding agencies to certain minimal standards of rationality.’").

Indeed, a court "need not find that the agency’s construction is the only possible one, or even the one that the court would have adopted in the first instance." Wyoming Outdoor Council, supra, 165 F.3d at 52. In Rollins, supra, 937 F.2d at 651, our Court of Appeals sustained an EPA interpretation of its own regulation that the court believed "would not exactly leap out at even the most astute reader," and was "rather more strained" than the plaintiffs’s reading of the regulation. The Court upheld the interpretation because it was consistent with the regulation and, "in a competition between possible meanings of a regulation, they agency’s choice receives substantial deference." Id. Here, in any event, the defendants’ interpretation of their own listing criteria is eminently reasonable.

1. The Final Descriptive Paragraph Of The 1996 Revised Listing Criteria Permits Consideration Of Human Mechanistic Data As Part Of The "Known" Category, And Permits Such Data To Support A Listing In The "Known" Category When Evidence From Epidemiological Data Alone Is Less Than Sufficient.

As part of its revisions to the 1996 criteria, a final descriptive or explanatory paragraph was added to the criteria that explicitly permits consideration of all relevant information, including mechanistic data. This final paragraph states:

Conclusions regarding carcinogenicity in humans or experimental animals are based on scientific judgment, with consideration given to al relevant information. Relevant information includes, but is not limited to dose response, route of exposure, chemical structure, metabolism, pharmacokinetics, sensitive sub populations [sic], genetic effects, or other data relating to mechanism of action or factors that may be unique to a given substance. For example, there may be substances for which there is evidence of carcinogenicity in laboratory animals but there are compelling data indicating that the agent acts through mechanisms which do not operate in humans and would therefore not reasonably be anticipated to cause cancer in humans.>

A review of the administrative history leading to the adoption of the revised criteria, as well as authoritative statements made thereafter, plainly show that, as a result of the addition of this final descriptive paragraph, a listing evaluation made under the "Known To Be A Human Carcinogen" category, (a) may properly consider "all relevant information," including mechanistic data in humans (or human mechanistic data), and (b) may properly conclude that a listing in the "Known" category may be based on less than sufficient epidemiological evidence combined with strong human mechanistic data.

(A) The 1996 Listing Criteria Revisions Permit Consideration Of Mechanistic Data In Support Of The "Known" Category.

First, it is clear that mechanistic data can be considered when listing a substance in the "Known" category. The "Known" category requires that there be sufficient evidence of carcinogenicity "from studies in humans." Plaintiffs argue that this language precludes the consideration of mechanistic data. Memorandum at 16-17⁹ But the language, "from studies in humans," may reasonably be interpreted to mean "from human studies." Human studies may reasonably be interpreted to include human mechanistic studies, that is, studies that show the mechanism by which dioxin works on and in human cells, and the connection such a mechanism has to cancer.

Moreover, this interpretation is fully supported by the administrative history of the adoption of the revised criteria. Revisions to the earlier listing criteria were first proposed at an April 24-25, 1995 meeting of the NTP Board of Scientific Counselors Ad Hoc Working Group. See Ex. 4, at 2; see also 7-27-95 Summary Minutes, Ex. 7, at 3 (referring to the April 24, 1995 meeting as the "first step in the criteria review process"). At that first meeting, one of the primary topics of discussion was the possible "incorporation of mechanistic data as part of the criteria for listing substances in future Reports...". Ex. 4, at 2 (emphasis added). Individual "bread-out" groups were assembled and each group commented on the topic. See generally Ex. 4.

Following the publication of the proposed revisions in the Federal Register on June 8, 1995, (60 Fed. Reg. 30435, Ex. 5), these comments were then presented and discussed at a June 29, 1995 NTP Board meeting. See Ex. 6. Following discussion and public comment, it was "moved that mechanistic information should be included in the selection process for agents to be listed in the [RoC]." Id. at 7 (emphasis added). The motion passed unanimously. Id. Nowhere during the discussions of mechanistic data was it agreed or decided that such data should be used only fr the "Reasonably Anticipated" and not for the "Known" category.

The references to mechanistic data were placed in an explanatory paragraph that was initially, and ultimately, placed at the end of the criteria. See Ex. 4, at 6; and see final criteria in DBD, Ex. 1, at LC-1. Plaintiffs argue that "there is no indication from either the format or the textual explanations that the descriptive paragraph with its references to mechanistic data applies to the ‘known’ category." Memorandum at 22.

This is flatly incorrect. The original proposed criteria show the explanatory paragraph with wider margins than either of the two specific listing categories, indicating by that format that they apply to both. See Ex. 4, at 6.¹⁰ Although in their papers for injunctive relief plaintiffs assign no meaning or purpose to the explanatory paragraph, they have previously asserted that the explanatory paragraph should apply only to the "Reasonably Anticipated" category due in part to its format. See Cmplt. Ex. 11 at 2.

This argument is belied by the fact that at one time during the revision process, a draft of the explanatory paragraph was placed above both specific listing criteria, thereby clearly precluding an argument that it applied only to the "Reasonably Anticipated." See Ex. 6, last page. The Minutes of the NTP Executive Committee Meeting on July 27, 1995, summarizing what had been done up to that point, show that the NTP Board had approved a resolution to place the "explanatory paragraph" at the beginning of the criteria. See ex. 7, at 4.

Although it was ultimately placed at the bottom again in the final draft, it is clear from its top to bottom movement, and from the surrounding statements about its use, that the explanatory paragraph was intended to apply to both categories. Even after the paragraph had been moved back to the bottom again, the minutes of the January 26, 1996 NTP Executive Committee Meeting clearly state that "Dr. Jameson then read a final paragraph which applies to all the criteria and discusses the role of scientific judgment, and other relevant information...". 1-26-96 Minutes (emphasis added), Ex. 10, at 8; see also 5-8-96 Minutes, Ex. 11, at 5.

Moreover, any argument that the text of the explanatory paragraph itself does not apply to the "Known" To Be A Human Carcinogen" category fails because the explanatory paragraph explicitly states that "Conclusions regarding carcinogenicity in humans ... are based on scientific judgment, with consideration given to ... data relating to mechanism of action..." Ex. 1, at LC-1. Thus, consideration whether a substance is known to be a human carcinogen may clearly be based on such data.

Not only does the administrative history, and logic¹¹ dictate that mechanistic data be used for the "Known" category, but the defendants’ own statements above the revised criteria following their publication show, with one minor exception, that defendants understood that mechanistic data was to be considered under the "Known" category. When the final, revised criteria were published in the Federal Register on September 26, 1996, the accompanying text there provided a brief summary of the review process. It stated that at "each step of the review process there was concurrence with the following points ... (2) mechanistic information should be used as part of the listing criteria." See 61 Fed. Reg. 50499. The Federal Register text also notes just above a printing of the descriptive paragraph containing the reference to mechanistic data that "the following descriptive paragraph has been added to the criteria." Id. Nowhere does the Federal Register text differentiate between the criteria for the "Known" category and the "Reasonably Anticipated" category. Thus, the descriptive paragraph reasonably applies to both categories.

Plaintiff points, however, not to the Federal Register Notice but to a staff authored press release in the "HHS News," entitled "Updated Criteria Approved For Anticipated Human Carcinogens." See Cmplt. Ex. 2. This press release did state that the criteria had been updated and mechanistic data was included for use in the "Reasonably Anticipated" category. It also stated, confusingly, that "the original criteria for listing a substance as a known human carcinogen remain unchanged...." Id. at 2. This second statement, which was not a quote from, or attributed to, anyone connected to the program, is both factually incorrect and misleading. It is factually incorrect because the actual literal text of the "Known" category did change from the previous version. See 61 Fed. Reg. 50449. It is also clearly misleading to the extent that it implies that the final descriptive paragraph does not apply to the "Known" category.

While the statement is misleading, it may be understood as referring solely to the text of the "Known" category itself. Even administrative references prior to the adoption of the revised criteria indicate that there were few or modest changes to the text of the "Known" category. E.g., 5-8-96 Minutes, Ex. 11, at 4. An NIEHS newsletter put out at the same time as the revised criteria makes the same point. See Cmplt. Ex. 3. On one hand the newsletter states that the "major change in the BRC is that the . . . NTP . . . will consider all relevant information - including mechanistic data - in determining whether to list a substance." See Cmplt. Ex. 3 (emphasis added). The newsletter did not state that mechanistic data could be used only to list a substance in the "Reasonably Anticipated" category. On the other hand the newsletter states that, with regard to the "Known" category, the revised criteria "are substantively unchanged," without referring to the final descriptive paragraph, and referring simply to the language under that heading.

The emphasis on the "Reasonably Anticipated" category makes sense in light of the opinion at the time that consideration of mechanistic data would have the biggest impact in connection with the "Reasonably Anticipated" category. Indeed, the NIEHS newsletter goes on to say that "[m]ost substances listed in the BRC are contained in the reasonably anticipated to be a human carcinogen’. . ." Id.

It is in this context that one should view the press release reference in the HHS News as well, i.e., it refers, albeit misleadingly, simply to the language of the category and does not make reference to the final descriptive paragraph. Dr. George Lucier, Director of the Environmental Toxicology Program at NIEHS, states that such statements "indicating that there was little or no change in the known human carcinogen’ category after publication of the criteria in September, 1996 related to the precise wording of the category only." See Lucier Dec., Ex. 15.

Notwithstanding the press release, the agency continued to clearly state that the final descriptive paragraph, with its reference to mechanistic data, applied to both categories. Shortly after the revised criteria were published, at the October 30, 1997 NTP Board Meeting, Dr. Lucier clearly stated that mechanistic data applied to both categories. See Ex. 12. He made similar comments in December, 1998, one year later, and noted specifically that mechanistic data "impact both categories." See Ex. 13. Thus, it is clear that mechanistic data is properly used during considerations for listing in the "Known" category.

(B) Mechanistic Data Can Support A Finding Of "Sufficient Evidence From Studies In Humans Which Indicates A Causal Relationship" Between Cancer and the Agent When The Epidemiological Data Is Less Than Sufficient.

Plaintiffs also argue that mechanistic data cannot support a finding of "sufficient evidence" of a "causal relationship," which is necessary in order to list a substance under the "Known" category, if the epidemiological evidence is less than sufficient by itself. Memorandum at 17-21. This is belied by the very words of the descriptive paragraph, which states that "Conclusions regarding carcinogenicity in humans . . . are based on scientific judgment, with consideration given to all relevant information . . . includ[ing] . . . data relating to mechanism of action" DBD at LC-1, Ex. 1. The ultimate decision is, obviously, left to "scientific judgment," and there is nothing to preclude NTP’s scientific judgment from finding that epidemiological evidence in conjunction with human mechanistic data may together rise to the necessary level of "sufficient evidence" indicating a "causal relationship."¹²

Moreover, although the explicit words of the final, descriptive paragraph by themselves preclude plaintiffs’ argument on this point, administrative history also explicitly supports the defendants’ interpretation. The Minutes of the June 29, 1995 NTP Board Meeting note that the explicit issue that plaintiffs now raise was raised then. The Minutes show that,

Dr. Lucier stated that a point of discussion might be whether there could be compelling mechanistic data that would allow a chemical to be classified a human carcinogen even though it may lack good epidemiological data. Dr. Carl Barrett, NIEHS Scientific Director, contended that a chemical or agent could be placed in Category 1, lacking convincing epidemiological evidence, if there was a consensus of experts that available mechanistic data strongly supported the chemical being a human carcinogen. June 29, 1995 Minutes, at 5, Ex. 6.

This exchange clearly shows that drafters of the revised criteria intended that mechanistic data could be used to support a finding in the "Known" category even where the traditional epidemiological evidence was less than "sufficient."¹³ Thus, it is clear both that (a) mechanistic data may be properly used to consider a listing under the "Known" category, and (b) that such data may, if the evidence supports it, be combined with limited human epidemiological data to jointly support a finding a "sufficient evidence" of a "causal relationship" between the agent and cancer.

That is exactly what the proposed listing for dioxin does. The epidemiological evidence is stated as showing an "association" between cancer and dioxin. DBD, RC-1, Ex. 1. The proposed listing goes on to state that this epidemiological evidence showed that industrial exposure to dioxin in the cohorts studied indicated an increased risk for all cancers in general, rather than for any one particular type of cancer. DBD, Ex. 1, ¶3.0, p. 3-1, 3-2. The DBD goes on to show, however, that there is "scientific consensus" relating to the mechanism of action data for dioxin. In particular, the mechanistic data studies indicate "that Ah receptor activation is required for the carcinogenicity of [dioxin]." Id. at p. 7-1. Mechanistic data also clearly shows that dioxin induces a wide spectrum of biological responses in both human and rodent cells, including cancer, by, as a necessary step, binding to an intracellular protein known as an "Ah receptor." Id. at RC-2 and ¶ 7.1. Thus, in the defendants’ scientific judgment, whose job it is to make exactly these types of toxicological judgments, this information together properly supports a listing of dioxin in the "Known" category.

Thus, knowing the above, it is useful to return briefly to plaintiffs’ arguments. First, the defendants did not rely on irrelevant factors in relying on mechanistic data, or on corroborative animal data. Nor did the agency depart from any pre-existing policy when it relied on this data. The only "departure" was the 1996 revision to the listing criteria, which has been fully explained.

B. The Evidence Supporting The Proposed "Known" Dioxin Listing Was Presented Accurately and Fully Supports The Listing.

Plaintiffs argue that the defendants did not present the evidence supporting the dioxin listing accurately and that the evidence does not support the listing. Memorandum at 25-30. Unlike plaintiffs’ first two arguments, this argument directly attacks the scientific support for the dioxin listing. The argument fails.

As defendants have already noted, when reviewing scientific judgments made by an agency charged with making such judgments, this court will not "substitute its own judgment for that of the agency." Citizens to Preserve Overton Park, Inc. v. Volpe, 401 U.S. 402, 416 (1971); Troy Corp. v. Browner, 120 F. 3d 277, 283 (D.C. Cir. 1997); see also Synthetic Organic Chemical Manufacturers Assoc. v. Secretary, Dep’t of Health & Human Services, 720 F.Supp. 1244, 120 (W.D.La. 1989). Indeed, the Court reviews scientific judgments of an agency "‘not as the chemist, biologist or statistician that [it is] qualified neither by training nor experience to be, but as a reviewing court exercising [its] narrowly defined duty of holding agencies to certain minimal standards of rationality.’". Troy, supra, 120 F.3d at 283.

Here, plaintiffs argue that the following DBD statement is inaccurate: "In the highly exposed industrial sub-cohorts, a causal relationship between TCDD exposure and mortality from all cancers combined was noted, but there was less strong evidence for cancers of any particular site." DBD at RC-1, Ex. 1. That reference is attributed to the IARC monograph at pages 192-93. See DBD at 3-2, Ex. 1. The IARC reference clearly states that two of the studies reviewed by IARC provided evidence "supporting a causal relationship between [dioxin] exposure and mortality from all cancers." Ex. 3, at 193. Thus, the reference is not inaccurate.

Plaintiffs argue that the DBD improperly presented this statement as IARC’s overall finding of the value of the epidemiological evidence. But this simply isn’t so. The DBD plainly states in the first sentence in section 3.0, dealing with epidemiological evidence that, "IARC (1997) stated that there is limited evidence from epidemiology studies of humans. . ." DBD at 3-1, Ex. 1. Thus, plaintiffs’ argument fails.

Plaintiffs next argue that the defendants should not have relied on two studies authored in 1997 and 1998 by Bertazzi et al. These studies follow, and periodically update, the toxicological effects of industrial workers exposed to dioxin as a result of a factory explosion in Seveso, Italy. See DBD Supplement at 2, Ex. 2. Plaintiffs argue that because IARC did consider an earlier, 1996 version of the Bertazzi studies, that IARC therefore somehow "considered" all the subsequent Bertazzi follow-up studies. This is simply not true. The bibliography to the IARC monograph shows that the 1997 and 1998 Bertazzi studies were not considered. See Ex. 3, at 531.

Moreover, plaintiffs’ argument that the Bertazzi studies, both new and old, do not support the dioxin "Known" listing must also fail. Plaintiffs cite to various submissions by, as well as an oral presentation by, Dr. Raymond Greenberg at the October 31, 1997 NTP peer review meeting, al of which criticize the Bertazzi studies.¹⁴ It was at that meeting, after hearing Dr. Greenberg’s presentation, that the assembled scientists voted to upgrade dioxin. See 63 Fed. Reg. 13418. The fact that Dr. Greenberg’s view ultimately did not carry the day does not mean that the evidence, either the Bertazzi studies or any other evidence, is insufficient. This is exactly the type of scientific judgment that this Court should not second guess. In any event, nowhere does the DBD state that the epidemiological evidence, such as the Bertazzi studies, are "sufficient" by themselves. Clearly, the dioxin listing is based on many epidemiological studies, and on the mechanistic data discussed above. See Supplemental DBD, listing additional sources not reviewed by IARC, Ex. 2.

Finally, plaintiffs argue that the proposed dioxin listing inappropriately relies on studies of exposure to dioxin mixtures, as opposed to 2,3,7,8-TCDD itself, i.e., "pure" dioxin. But the defendants have previously responded to this issue and made it clear that they "placed greater weight n those studies which have used TCDD blood levels as the exposure index rather than those which use the workplace situation." See 8-24-98 Letter from Olden to Tozzi, Cmplt. Ex. 17. Thus, the proposed dioxin listing has a valid scientific basis, and plaintiffs’ efforts to criticize it must fail.

III. Plaintiffs Have Failed To Show Any Irreparable Injury.

Quite separate and apart from plaintiff’s lack of likelihood of success n the merits, is the plain fact that plaintiff’s lack of likelihood of success on the merits, is the plain fact that plaintiffs have proffered only the most speculative type of economic harm. For this reason alone plaintiffs’ motion for a preliminary injunction should fail.¹⁵

In order to qualify for preliminary injunctive relief, plaintiffs must show that they will suffer irreparable injury in the absence of such relief. But "[i]rreparability of injury is a very high standard." Bristol-Meyers Squibb Co. v. Shalala, 923 F.Supp. 212, 220 (D.D.C. 1996) (internal citation omitted). Here, plaintiffs now argue that the proposed agency action they seek to enjoin:

Will create public confusion and concern over the safety of the food Plaintiffs serve. This public confusion and concern will lead to some degree of consumer aversion to meats, fish and dairy products Plaintiffs serve, thereby reducing sales. Plaintiffs will also incur increased costs associated with attempting to dispel such public confusion and concern, as well as disruptions and increased costs in their food supply chain. Memorandum at 31.

This claim of harm fails for two basic reasons; it is speculative, and even if it did occur, it would be insufficient to constitute "irreparable" harm and could not justify injunctive relief.

First, the claimed harm is speculative. As our Court of Appeals explained, to constitute irreparable harm, the injury must be certain and great; it must be actual and not theoretical. Wisconsin Gas Co. v. FERC, 758 F.2d at 674. Injunctive relief will not be granted against something merely feared as liable to occur at some indefinite time; rather, the movant must substantiate the claim that the irreparable injury is likely to occur:

Bare allegations of what is likely to occur are of no value since the court must decide whether the harm will in fact occur. The movant must provide proof that the harm has occurred in the past and is likely to occur again, or proof indicating the harm is certain to occur in the near future. Further, the movant must show that the alleged harm will directly result from the action which the movant seeks to enjoin.

758 F.2d at 674.

As defendants have previously argued at some length,¹⁶ there simply is no support for the claim that, were dioxin to be listed and published in the RoC under the "Known To Be A Human Carcinogen" category, the general public will swear off meats, fish, and dairy products as part of a "food scare." The carcinogenicity of dioxin has already been well publicized and plaintiffs have suffered no harm as of yet. As plaintiffs well know, IARC, a highly respected subgroup of the World Health Organization, in a well publicized monograph, has already listed dioxin in its highest category as "carcinogenic to humans." IARC monograph, Ex. 3, at 343. Similarly, large metropolitan areas, such as Oakland and San Francisco, California, have passed ordinances declaring dioxin to be the "single most carcinogenic substance known to science.," Cmplt. Exs. 5 & 6. Plaintiffs have suffered no injury yet, and provide no basis for believing that anything different will happen following publication of the RoC, should it ultimately list dioxin under the "Known" category.

Moreover, plaintiffs’ comparisons to reports concerning dioxin-contaminated sources for Belgian livestock and poultry are inapposite. Memorandum at 34, Such reports relate to specific high level contaminations and specific foods. The proposed RoC listing for dioxin relates to no particular use for or source of dioxin. Nor could consumers really avoid dioxin altogether in any event, given its ubiquity. See DBD, Ex. 1, ¶2,.3, p. 2-2. (Stating dioxin most likely spread to soil through "atmospheric fallout"). Thus, plaintiffs’ asserted "food scare" is totally speculative.

Second, even if there were, as plaintiffs argue, "some degree of consumer aversion" to meat, fish and poultry as a result of the RoC, such aversion is completely inadequate to show irreparable injury. "It is well settled that economic loss does not, in and of itself, constitute irreparable harm. . . . ‘The key word in this consideration is irreparable. Mere injuries, however substantial in terms of money, time and energy necessarily expended in the absence of a stay are not enough.’" Bristol-Myers, supra, 923 F.Supp. at 220 (quoting Wisconsin Gas, supra, 758 F.2d at 774).

Courts apply "[d]emanding scrutiny" to claims of irreparable injury. Bristol-Myers, supra, 923 F.Supp. at 220. In CityFed Fin. Corp. v. OTS, 58 F.3d 738, 747 (D.C. Cir 1995), our Court of Appeals affirmed the denial of injunctive relief even when the defendant Office of Thrift Supervision had completely frozen plaintiff’s assets, and in the face of plaintiffs’ claim of bankruptcy, because the court found that plaintiff could apply for "hardship" relief.

Plaintiffs argue that they have shown irreparable injury because they will be unable to recover money damages from the government. But this fact alone does not obviate plaintiffs’ need to show "severe economic impact." Bristol-Myers, supra, 923 F.Supp. at 221 (quoting WMATC v. Holiday Tours, Inc., 559 F.2d 841, (D.C. Cir. 1977)). Plaintiffs have failed to show anything close to severe economic impact. E.g., Varicon Int. Mgmt. V. OPM, 934 F.Supp. 440, 448 (D.D.C. 1196) (ten percent loss of business insufficient to show irreparable harm); Arrow Air, Inc v. United States, 649 F.Supp. 993 (D.D.C. 1986) (twenty-five percent loss of gross revenue insufficient to show irreparable harm); Mead Johnson Pharm. Group v. Bowen, 655 F.Supp. 53 (D.D.C. 1986) (twenty to thirty percent loss of market share not show irreparable harm). Rather, plaintiffs’ claim of a "food scare" is speculative, and there is nothing to suggest that plaintiffs would lose more than a de minimis amount of business as a result of the dioxin listing in the RoC. See Bristol-Myers, supra, 923 F.Supp. at 221.

Plaintiffs understandably seek to avoid the requirement that they show significant economic impact by relying on cases where injunctions have been granted enjoining the release of information that would damage a plaintiff’s business reputation. Memorandum at 32-33.¹⁷ Such cases are completely inapposite here, however, because any link between the plaintiffs’ restaurants and publication of the RoC is totally speculative. The cases plaintiffs cite relate to release of information that would be specifically damaging to the plaintiff’s business. E.g., Honeywell, Inc. v. Consumer Product Safety Comm’n, 582 F.Supp. 1072, 1073 (D.D.C. 1984) (Manufacturer of gas control products sought to prevent document describing its product as a hazard); GTE Sylvania, Inc. v. Consumer Product Safety Comm’n, 404 F.Supp. 352, 378 (D,Del. 1975) (TV manufacturers sought to prevent release of accident, safety and trade secret information about TVs); Dow Chemical, USA v. Consumer Product Safety Comm’n, 459 F.Supp. 378 394 (W.D.La. 1978) (chemical manufacturers sought to prevent certain classification of their own chemical products). Here, however, plaintiffs have failed to show why their reputations would in any way be damaged by the RoC, which neither refers to any of the plaintiffs or their businesses or to any product that they sell.¹⁸

Moreover, plaintiffs reference to Malarkey-Taylor Assoc., Inc. v. Cellular Telecommunications Indus. Ass’n., 929 F.Supp. 473, 478 (D.D.C. 1996), for the proposition that business reputation may be damaged by "consumer confusion" is equally inapposite. Malarkey-Taylor was a trademark infringement case where the issue of confusion between products was the central issue in the case. No such issue is presented here.

There is no support in any of the cases cited by plaintiffs that would serve to obviate the requirement, which plaintiffs plainly cannot meet, that they show significant economic damage prior to issuance of an injunction. Moreover, plaintiffs have failed to show that publication of the dioxin listing in the RoC would result in any damage to their business reputation.

D. Balancing The Harms Weighs Against Issuing An Injunction.

As part of its injunctive relief analysis, the Court must balance the relative harms to the parties of issuing an injunction. See Bristol-Myers, supra, 923 F.Supp. at 221. Here, were an injunction to issue, likely the entire RoC might have to be delayed, given the uncertain space allocation, pagination and other printing requirements relating to the dioxin portion of the report. Withholding the entie RoC based on the speculative claims proffered herein presents a greater harm t the defendants and the public at large than publication would cause to the plaintiffs, given the large public expenditure of money thus far and the speculative nature of plaintiffs’ claims.

E. The Public Interest Weights Against Issuing An Injunction.

Plaintiff has failed to establish that the public interest would be better served by issuing an injunction. The RoC is Congressionally mandated, and provides a necessary and important public service. Its publication in a timely fashion, after full and complete scientific deliberation should not be delayed based on speculative arguments claiming that it will result in a "food scare."

CONCLUSION

Because the defendants have properly evaluated all relevant data in considering the proposed dioxin listing under the "Known To Be A Human Carcinogen" category, sand because plaintiffs have failed to satisfy the requirements for preliminary injunctive relief by failing to show, in particular, a likelihood of success on the merits and any irreparable injury, their motion for preliminary injunction should be denied.

Respectfully Submitted,

___________________________________
WILMA A. LEWIS, DC Bar #3568637
United States Attorney

____________________________________
MARK E. NAGLE, DC Bar #416364
Chief, Civil Division

____________________________________
DAVID L. SMITH, DC Bar #453709
Assistant United States Attorney
555 4^th Street, N.W., Room 10-452
Washington, DC 20001
202/353-9895

Of Counsel:
Patricia A. Kvochak, Esq.
Office of General Counsel
National Institutes of Health

¹ Plaintiffs in this action are Beduci, a Washington, D.C. restaurant, Greenbaum & Gilhooley's a New York restaurant, the Empire State Restaurant & Tavern Association, and Jim Tozzi, an individual business and investor in of the restaurants.

² Defendants in this action are the United States Department of Health and Human Services ("HHS"); Donna E. Shalala, Secretary of HHS; Kenneth Olden, Director, National Institute of Environmental Health Sciences ("NIEHS") and Director, National Toxicology Program ("NTP"); and George W. Lucier, Director, Environmental Toxicology Program ("ETP").

³ Any evaluation of the merits of plaintiffs' claims assumes that the Court has jurisdiction to review the defendants' actions thus far. As the defendants have previously argued, however, this Court lacks jurisdiction to review the RoC, at the very least prior to its publication, under the APA, 5 U.S.C. § 704; State of California v. Department of Justice, 114 F.3d 1222 (D.C. Cir. 1997), and the ripeness doctrine. Ohio Forestry Association v. Sierra Club, 523 U.S. 726, 118 S.Ct. 1665, 1670 (1998); Pfizer, Inc. v. Shalala, WL 498553, 7-16-99, (D.C. Cir.). While it is true that the very purpose of injunctive relief is to prevent a threatened harm, the Court must still have an independent jurisdictional basis to take action. Here, the APA does not support jurisdiction and plaintiff does not seek a mandamus. Nor should mandamus relief be granted in this circumstance in any event. See 28 U.S.C. § 1361; e.g., Hanek v. Secretary of HEW, 535 F.2d 1291, 1296 (D.C. Cir. 1976); In Re Tripati, 836 F.2d 1406, 1407 (D.C. Cir. 1988). Thus, while defendants respond herein to plaintiffs substantive arguments, they do not waive their jurisdictional objections. Moreover, as a practical matter it makes little sense to review, for instance, the language in the Draft Background Document until such language is finally approved.

⁴ Epidemiological evidence is evidence arising from the study of living humans who were exposed to the substance being considered. Typically, for instance, an epidemiological study would follow a cohort individuals exposed to a particular substance to see, over time, what cancers or other symptoms they developed. Mechanistic data includes evidence arising from the study of the agent as it reacts on the cellular and molecular level.

⁵ That process was described at length in the defendants' Memorandum In Support of its Motion to Dismiss and will not be repeated here. Within the Department of Health and Human Services, the responsibility for preparing the Reports has been delegated by the Secretary of HHS to the National Toxicology Program (NTP). Dr. Kenneth Olden is the Director, National Toxicology Program, as well as the Director, National Toxicology Program, as well as the Director, National Institute of Environmental Health Sciences (NIEHS). Both programs are located in Research Triangle Park in North Carolina. NIEHS is one of the institutes of the National Institutes of Health. Dr. George Lucier is Associate Director of the NTP and his staff is primarily responsible for the review and drafting of the RoC.

⁶ Although the defendants cannot predict exactly when the Ninth RoC will be published, based upon past history of the length of time for the remaining levels of review, defendants estimate that the Ninth RoC could be published sometime in the November, 1999 to January, 2000 time frame.

⁷ Moreover, to the extent plaintiffs also complain about the reference to animal data in the proposed dioxin listing, virtually every substance listed under the "Known" category in prior RoCs makes corroborative reference to animal data. Such references, as supportive of the human findings, are perfectly proper, as explained below.

⁸ See Chevron U.S.A. Inc. v. Natural Resources Defense Council, Inc., 467 U.S. 837 (1984) (Outlining a two-step analysis statute that Congress has entrusted to the agency for implementation.)

⁹ Again, to the extent that plaintiffs also argue that defendants erroneously relied on animal data, as well as mechanistic data, this argument is also meritless. Memorandum at 16-17. A review of virtually every listing the 8th RoC under the "Known" category shows that reference is made to animal data, often as the very first thing mentioned. Animal data that corroborates either epidemiological data or mechanistic data, or both as here, is never precluded as additional support, above and beyond what is required, for a "Known" listing.

¹⁰ Plaintiffs base their argument on the fact that in the Federal Register the margins f the explanatory paragraph are not widened. But there appears to be no way to have done this given the constraints of the narrow columns in the Federal Register. Moreover, the versions printed by the agency, prior to its release in the Federal Register, al show the explanatory paragraph with widened margins. For instance, one version dated September 13, 1996, the very day the Secretary finally approved the criteria, shows the final paragraph with widened margins. Cmplt. Ex. 10 at p. 20.

¹¹ It simply makes no sense that, after lengthy debate and discussion, the defendants would preclude the use of mechanistic data, a powerful and emerging tool in toxicologic analysis, for consideration under the "Known" category, which is the highest listing category possible.

¹² That is, of course, if the evidence may scientifically support such a conclusion. Plaintiffs assert in their third argument, discussed below, that the evidence for dioxin falls short. They are incorrect.

¹³ Although the reference was to "Category 1," rather than to the "Known" category, it is clear from later references in the same paragraph to "Category 2" that these statements were intended to refer to the "Known" and "Reasonably Anticipated" categories.

¹⁴ Dr. Greenberg was representing the American Forestry and Paper Association in October, 1997 during his oral presentation, (see plaintiffs' Ex. 14), and was representing the Chlorine Chemistry Council in November, 1998 when he submitted various written recommendations. Plaintiffs' Ex. 13.

¹⁵ Thus, even if the plaintiffs were likely to succeed on the merits, which they are not, their failure to make the separate and independent showing of irreparable harm necessarily scuttles their claim for injunctive relief. See Sea Containers Ltd. v. Stena AB, 890 F.2d 1205, 1210-11 (D.C. Cir. 1980) (affirming denial of injunctive relief where plaintiff may have been likely to succeed but failed to show irreparable injury).

¹⁶ This argument is separate from, although factually relevant to, defendants' jurisdictional and constitutional arguments that plaintiffs lack standing. See Defendants' memorandum In Support of Motion To Dismiss at 21-25.

¹⁷ Plaintiffs also cite to Serono Laboratories, Inc. v. Shalala, 974 F.Supp. 29 (D.D.C. 1997). Indeed, it is the first case they cite. Memorandum at 31. But it is no help to them as the injunction issue therein was vacated on appeal. See Serono Laboratories, Inc. v, Shalala, 158 F.3d 1313 (D.C. Cir. 1998).