Daily Rules, Proposed Rules, and Notices of the Federal Government
In this document EPA denies an objection by the Natural Resources Defense Council (NRDC) concerning
• Crop production (North American Industrial Classification System (NAICS) code 111), e.g., agricultural workers; greenhouse, nursery, and floriculture workers; farmers.
• Animal production (NAICS code 112), e.g., cattle ranchers and farmers, dairy cattle farmers, livestock farmers.
• Food manufacturing (NAICS code 311), e.g., agricultural workers; farmers; greenhouse, nursery, and floriculture workers; ranchers; pesticide applicators.
• Pesticide manufacturing (NAICS code 32532), e.g., agricultural workers; commercial applicators; farmers; greenhouse, nursery, and floriculture workers; residential users.
You may access a frequently updated electronic version of EPA's tolerance regulations at 40 CFR part 180 through the Government Printing Office's e-CFR site at
In this order, EPA is issuing a revised denial of an objection to an earlier EPA order, (72 FR 68662, December 5, 2007), denying a petition to revoke all tolerances established for the pesticide dichlorvos (DDVP) under the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a. Both the objection as well as the petition was filed with EPA by NRDC. (Refs. 1 and 2). EPA had previously denied this objection, (73 FR 42683, July 23, 2008), but that order was vacated, in part, by the United States Court of Appeals for the Second Circuit. (
NRDC's petition, filed on June 2, 2006, pursuant to FFDCA section 408(d)(1), asserted numerous grounds as to why the dichlorvos tolerances allegedly fail to meet the FFDCA's safety standard. This petition was filed as EPA was completing its reassessment of the safety of the dichlorvos tolerances pursuant to FFDCA section 408(q). (Ref. 3). In response to the petition, EPA undertook an extensive review of its dichlorvos safety evaluation in the tolerance reassessment decision. Based on this extensive review, EPA concluded that dichlorvos met the FFDCA safety standard and, therefore, denied the petition. (72 FR 68695). NRDC then filed objections with EPA to the petition denial order and requested a hearing on its objections. The objections narrowed NRDC's claims to two main assertions—that, in assessing the risk to dichlorvos, EPA unlawfully reduced the statutory tenfold (10X) additional safety factor for the protection of infants and children and EPA unlawfully relied on a human toxicity study (the Gledhill study). After carefully reviewing the objections and hearing requests, EPA determined that NRDC's hearing requests did not satisfy the regulatory requirements for such requests and that its substantive objections were without merit. (73 FR 42709-42711). NRDC sought review of EPA's decision in the United States Court of Appeal for the Second Circuit. As noted, the Second Circuit court vacated a portion of EPA's order finding that “[b]ecause EPA failed to explain why it did not use a 10X children's safety factor for dichlorvos risk assessments that relied on the Gledhill study, EPA acted in an arbitrary and capricious manner.” (658 F.3d at 218). Specifically, the court vacated “those portions of EPA's July 23, 2008 order assessing the risk of dichlorvos based on the Gledhill study * * * ” (Id.). The court remanded the matter to EPA. (Id. at 219).
On remand, EPA has carefully examined the court's opinion and has reconsidered that portion of its prior decision that relied on the Gledhill study in assessing dichlorvos risk. Because the court found this portion of EPA's order to be arbitrary and capricious due to its absence of an adequate explanation on the additional safety factor for the protection of infants and children, EPA focused on a reexamination of what additional safety factor for the protection of infants and children should be applied for the assessments based on the Gledhill study. EPA concludes, like it did in the July 23, 2008 order, that a threefold (3X) additional safety factor will protect the safety of infants and children. Accordingly, EPA again denies NRDC's objections as to those portions of the July 23, 2008 order that were vacated. Although EPA reaches the same conclusion on remand on the additional safety factor for the protection of infants and children, EPA has provided a revised, more extensive explanation for its position. Because this revised explanation addresses the court's reason for finding portions of the July 23, 2008 order to be arbitrary and capricious, EPA has not otherwise reopened or reconsidered that prior order.
NRDC petitioned to revoke the dichlorvos tolerances pursuant to the petition procedures in FFDCA section 408(d)(1). (21 U.S.C. 346a(d)(1)). Under section 408(d), EPA may respond to such a petition by either issuing a final or proposed rule modifying or revoking the tolerances or issuing an order denying the petition. (21 U.S.C. 346a(d)(4)). Here, EPA responded by issuing an order under section 408(d)(4)(iii) denying the petition. (72 FR 68622, December 5, 2007).
Orders issued under section 408(d)(4)(iii) are subject to a statutorily-created administrative review process. (21 U.S.C. 346a(g)(2)). Any person may file objections to a section 408(d)(4)(iii) order with EPA and request a hearing on those objections. (Id.). EPA is required by section 408(g)(2)(C) to issue a final order resolving the objections to the section 408(d)(4)(iii) order. (21 U.S.C. 346a(g)(2)(C)). NRDC filed objections to EPA's denial of its dichlorvos petition and EPA issued a section 408(g)(2)(C) order denying NRDC's objections. (73 FR 42683, July 23, 2008). EPA's order denying NRDC's objections was vacated, in part, and remanded to EPA. This revised order on remand is also being issued under section 408(g)(2)(C).
In this Unit, EPA provides background on the relevant statutes and regulations governing the matter on remand as well as a much-abbreviated discussion on pertinent Agency risk assessment policies. A full discussion of EPA's approach to pesticide risk assessment is included in EPA's prior order on NRDC's objections. (73 FR 42685-42688). Because the court's decision focused on the explanation offered by EPA for its use of safety factors, this Unit includes an expanded discussion on use of safety or uncertainty factors, including the additional safety factor required by the FQPA for the protection of infants and children. Further, because Benchmark Dose Methods analysis is discussed for the first time in this revised order, a short section explaining that concept is included.
EPA also regulates pesticides under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), (7 U.S.C. 136 et seq). While the FFDCA authorizes the establishment of legal limits for pesticide residues in food, FIFRA requires the approval of pesticides prior to their sale and distribution, (7 U.S.C. 136a(a)), and establishes a registration regime for regulating the use of pesticides. FIFRA regulates pesticide use in conjunction with its registration scheme by requiring EPA review and approval of pesticide labels and specifying that use of a pesticide inconsistent with its label is a violation of Federal law. (7 U.S.C. 136j(a)(2)(G)).
Risks to infants and children are given special consideration. Providing additional protection to infants and children was a particular focus of the FQPA. Section 408(b)(2)(C) requires EPA to make a specific determination regarding the safety of tolerances to infants and children and to consider, among other things, information “concerning the special susceptibility of infants and children to the pesticide chemical residues * * *.” (21 U.S.C. 346a(b)(2)(C)(i)(II) and (ii)(II)). This provision also creates a presumptive additional safety factor for the protection of infants and children. Specifically, it directs that “[i]n the case of threshold effects, * * * an additional tenfold margin of safety for the pesticide chemical residue and other sources of exposure shall be applied for infants and children to take into account potential pre- and post-natal toxicity and completeness of the data with respect to exposure and toxicity to infants and children.” (21 U.S.C. 346a(b)(2)(C)). EPA is permitted to “use a different margin of safety for the pesticide chemical residue only if, on the basis of reliable data, such margin will be safe for infants and children.” (Id.). For convenience's sake, the legal requirements regarding the additional safety margin for infants and children in section 408(b)(2)(C) are referred to throughout this Order as the “FQPA safety factor for the protection of infants and children” or simply the “FQPA safety factor.”
Once EPA takes final action on the petition by establishing, amending, or revoking the tolerance or denying the petition, any party may file objections with EPA to EPA's decision on the petition and seek an evidentiary hearing on those objections. (21 U.S.C. 346a(g)(2)). Objections and hearing requests must be filed within 60 days. (Id.). The statute provides that EPA shall “hold a public evidentiary hearing if and to the extent the Administrator determines that such a public hearing is necessary to receive factual evidence relevant to material issues of fact raised by the objections.” (21 U.S.C. 346a(g)(2)(B)). EPA regulations make clear that hearings will only be granted where it is shown that there is “a genuine and substantial issue of fact,” the requestor has identified evidence that “would, if established, resolve one or more of such issues in favor of the requestor,” and the issue is “determinative” with regard to the relief requested. (40 CFR 178.32(b)). Further, a party may not raise issues in objections unless they were part of the petition and an objecting party must state objections to the EPA decision and not just repeat the allegations in its petition.
Toxicological hazards posed by a pesticide are identified through use of testing in laboratory animals or humans. Generally, EPA will use the lowest “no observed adverse affect level” (NOAEL) or “lowest observed adverse effect level” (LOAEL) from the available studies or a calculated value called a Benchmark Dose as a starting point (called “the Point of Departure”) in estimating the “level of concern” for human exposure to the pesticide. Points of Departure and levels of concern will be identified for all exposure routes to the pesticide (oral, dermal, and inhalation) and durations of exposure (acute, short-term, intermediate-term, and chronic). Another critical aspect of the “level of concern” determination involves the use of safety or uncertainty factors to compensate for the limitations of toxicology testing. Safety and uncertainty factors are discussed in detail in Unit III.B.2. below. Having identified a pesticide's hazards, the Point(s) of Departure, and level(s) of concern, EPA then estimates exposure to the pesticide taking into account the various routes of exposure, how exposures vary over time, and the differences in exposure to different subpopulations. Finally, EPA combines information on hazard, level of concern, and exposure to produce a characterization of the risk posed by the pesticide. Risks are calculated for all of the various routes and durations of exposure scenarios associated with a pesticide. These risk assessment
Before turning to a detailed discussion of safety and uncertainty factors, EPA's risk characterization process is briefly summarized because it is frequently referred to in this order. For pesticides that pose a risk over a certain threshold of exposure, EPA's characterization of risk is presented in one of two ways: Either using the Reference Dose (RfD) approach or the Margin of Exposure (MOE) approach. Importantly, these different approaches do not render substantively different results. Both approaches use the same data—the Point of Departure, the applicable safety/uncertainty factors, and human exposure to the pesticide; they just express the characterization of risk in a different metric. Under the RfD approach, EPA directly extrapolates a dose from an animal or human study to an overall safe dose for humans. An RfD is calculated by dividing all applicable safety/uncertainty factors into the level of exposure from animal or human studies determined appropriate for assessing risk (i.e., the “Point of Departure”). Estimated human exposure to the pesticide is then compared to the RfD to determine if it is excessive. Under the Margin of Exposure (MOE) approach, EPA does not calculate a safe dose in humans but rather focuses on the margin of exposure between a dose from an animal or human study and human exposure to the pesticide. A MOE is calculated by dividing human exposure to the pesticide into the Point of Departure. To determine whether that MOE is considered sufficiently protective of humans, EPA compares it to the product of all applicable safety/uncertainty factors, referred to as the target MOE. MOEs that are less than the target MOE indicate a risk of concern. At bottom, both approaches extrapolate a safe measure of human exposure from animal or human studies using a mixture of uncertainty/safety factors.
The interspecies uncertainty factor can be considered to convert the NOAEL/NOAEC [No observed adverse effect concentration] for animals (derived from a small group of relatively homogeneous test animals) into the NOAEL/NOAEC anticipated for an average representative healthy human. The uncertainty factor for human variability converts the NOAEL/NOAEC for the average human into a NOAEL/NOAEC for susceptible humans. Although adverse effect data in humans can be used directly without the need for an interspecies factor, the paucity of such data means that the vast majority of risk assessments are based on studies in experimental animals.
EPA, as well as other Federal and international regulatory bodies, also will, where appropriate, apply additional numerical factors to take into account chemical-specific considerations affecting the risk assessment. (Ref. 9) Use of these additional factors is further explained in Unit III.B.2.v., vi, and vii.
One reason humans are considered to be potentially more sensitive to toxic agents than laboratory animals is that otherwise equivalent external doses of such agents for humans and animals on a milligram-per-kilogram of body weight basis may result in a greater internal dose for humans. This is due to species differences in general metabolic processes—commonly referred to as toxicokinetics—and “is thought to be related to species differences in exchange surfaces and distribution networks that constrain concentration and flux of metabolic reactants.” (Ref. 19 at 4-35; see Ref. 15 at 228).
In addition to toxicokinetic effects on internal dose, differences between humans and laboratory animals are also driven by toxicodynamic factors. Toxicodynamics refers to the manner in which the target tissue and body respond to the toxic agent. Thus, interspecies differences are a factor of both differences in the internal dose received by humans and animals and differences in how humans and animals react to the internal dose received. Similarly, sensitivity differences between juveniles and adults, whether humans or animals, are also considered to be tied to toxicokinetic and toxicodynamic factors. Accordingly, both the inter- and intraspecies uncertainty factors are considered to have toxicokinetic and toxicodynamic components. EPA typically has considered both the tenfold (10X) inter- and intraspecies factors to be roughly equally divided on a logarithmic basis (i.e., 10
Of the toxicokinetic and toxicodynamic differences between humans and animals and among various human subgroups, the most is known about the toxicokinetic differences between humans and animals. For inhalation exposures, EPA has used toxicokinetic information on humans and animals to create generic dosimetric adjustment factors that replace that portion of the interspecies factor tied to toxicokinetic differences. (Refs. 19 at 4-29; 20). Where such dosimetric adjustment factor is used, the interspecies factor is reduced to 3X.
EPA guidance entitled “A Review of the Reference Dose and Reference Concentration Processes” (“RfD Guidance”) also urges that data be developed to support substitution of chemical-specific adjustment factors (sometimes referred to as data-derived factors) for the default 10X uncertainty factors for inter- and intraspecies variability. (Ref. 19 at xviii -xix, 4-47). This guidance recognizes that chemical-specific data from both humans and animals has been relied upon by EPA to adjust the human intraspecies uncertainty factor citing an article by Dourson et al. That article collects instances in which EPA has adjusted uncertainty factors on a chemical-specific basis. (Ref. 9). For example, Dourson et al. point to a 1996 EPA assessment of Aroclor that reduced the human intraspecies factor to 3X given that the Point of Departure came from a sensitive animal population—there, infant rhesus monkeys. In discussing the Dourson et al. article, the RfD Guidance notes that:
In those cases where developmental effects were the most sensitive endpoint (0 RfCs, 6 RfDs), reduction of the intraspecies [uncertainty factor] from 10 to 3 was based on data derived either from human data showing which age groups or time periods were most susceptible (e.g., methyl mercury exposure to the developing fetus) or from an animal study with support from strong human or other data (e.g., Aroclor 1016 in utero exposure in monkeys, strontium-induced rachitic bones in young rats).
In sum, the 10X inter- and intraspecies factors are default values. Although there is substantial scientific support for these default values, chemical-specific human and animal data may be relied upon in reducing, confirming, or increasing these default values.
The protectiveness of these default values has also been the subject of scientific examination. Studies have been done on the variations in the levels of NOAELs in the databases for various pesticides. They confirm the need for an additional factor when core data are lacking. (Ref. 22). Examination of the completeness of the animal database remains important even when human data are used as the Point of Departure for calculating the RfD. The latest EPA guidance on RfDs emphasizes that in
Selection of particular values for these additional uncertainty values depends on what is known from the full body of information about the chemical, including both data from testing with animals and humans, about the chemical. For example, as EPA's RfD Guidance advises: “the size of the database factor to be applied will depend on other information in the database and on how much impact the missing data may have on determining the toxicity of a chemical and, consequently, the POD [Point of Departure].” (Ref. 19 at 4-45). With regard to an additional factor for extrapolation of a NOAEL from a LOAEL, Dourson et al. report that “[a]nalysis of several data bases suggest that a factor of 10 or lower is adequate and that use of data does support a lower factor with certain chemicals.” (Ref. 9 at 112). The critical consideration, according to Dourson et al., is the severity of the effect at the LOAEL: “The data indicate that when faced with a LOAEL and not a NOAEL, the choice of uncertainty factor should generally depend on the severity of the effect at the LOAEL.” (Id.). Specifically, Dourson et al. note that “[l]ess severe effects would not require a large factor, because, presumably, the LOAEL is closer to the unknown NOAEL.” (Id.).
The narrowly-focused and highly-prescriptive nature of the FQPA safety factor provision has required careful integration with pesticide risk assessment approaches under other statutes and, more generally, with Agency risk assessment practices. As noted above, the FQPA, with regard to the assessment of risks to infants and children, essentially codified EPA's prior risk assessment practice as to additional uncertainty factors and it expanded the use of additional uncertainty factors into new areas. The FQPA, however, did not speak to use of traditional (non-additional) uncertainty factors (i.e., the inter- and intraspecies factors). Thus, the end result was that some uncertainty factors for FFDCA pesticides remained unaffected by the new statutory requirements (the inter- and intraspecies factors), some uncertainty factors became FQPA safety factors (additional uncertainty factors that addressed toxicity data deficiencies), and some safety factors that either had previously never existed or were at least extremely rare were created as a statutory phenomenon (a factor to address exposure data base deficiencies and a factor to address potential pre- and post-natal toxicity). This selective inter-weaving of statutory requirements with Agency science policy made FFDCA risk assessments for pesticides unique compared to general Agency risk assessment practice.
Pesticide risk, however, is not regulated under a single statute. Risks to workers or the environment from pesticide use are regulated by EPA under FIFRA, not the FFDCA. Further, EPA may address risks posed by pesticide contamination of the environment under several other statutes, including the Safe Drinking Water Act, 42 U.S.C. 300f et seq., the Resource Conservation and Recovery Act, 42 U.S.C. 6901 et seq., and the Comprehensive Environmental Response, Compensation, and Liability Act, 42 U.S.C. 9601 et seq. Prior to enactment of the FQPA's specific provisions on pesticide risk assessment, a pesticide risk assessment performed by EPA's Office of Pesticide Programs under the aegis of FFDCA section 408 could generally be easily translated for use by the Office of Pesticide Programs under FIFRA, or by the other media offices within EPA for use under other statutes. However, once pesticide risk assessment under the FQPA became not simply a matter of good scientific practice but was channeled by explicit statutory requirements, it became incumbent upon the Office of Pesticide Programs to prepare its FFDCA pesticide risk assessments in a manner that clearly delineated what aspects of the assessment were driven solely by science and what aspects primarily by FQPA statutory requirements. Specifically, the Office of Pesticide Programs had to be transparent with regard to whether it was relying on FQPA safety factors based on unique FQPA requirements (exposure database deficiencies and potential pre- and post-natal toxicity) or FQPA safety factors that are essentially a codification of prior general EPA “additional” safety/uncertainty factor practice.
EPA addressed these transparency issues at length in its 2002 policy statement on the FQPA safety factor. To clarify how the FQPA safety factor provision left a portion of prior safety/uncertainty practice unchanged, codified another portion, and also expanded the use of safety factors, EPA explained the overlap between the FQPA safety factor and additional safety factors in depth and included the following figure to graphically illustrate the issue:
With regard to providing transparency on the FQPA safety factor decisions, EPA took two steps. First, it adopted a new term, the “special” FQPA safety factor, for children safety factors that were based solely on the new FQPA requirements. Second, it adopted the approach of calculating two different safe doses for a pesticide: one that excluded any “special” FQPA safety factors and one that included them. The former was referred to, in line with standard EPA policy, as a Reference Dose (RfD), and the latter as a Population Adjusted Dose (PAD). Introducing the new terminology on FQPA safety factors into long-established safety factor practice has proved challenging. EPA staff on occasion drafted documents that (1) claimed no FQPA safety factor was needed but applied an additional uncertainty factor to address the completeness of the toxicity data base or reliance on a LOAEL; or (2) treated the “special” FQPA safety factor as the only type of FQPA safety factor. However, as EPA's policy made clear, EPA interpreted FFDCA section 408(b)(2)(C) as codifying prior practice as to additional uncertainty factors such that these factors became FQPA factors. The mislabeling of uncertainty factors did not substantively change risk assessment outcomes but it did raise the confusion level on an already complex topic. Eventually, EPA determined that the term “special” FQPA safety factor caused more problems than it solved and abandoned it. However, EPA has retained the approach of continuing to calculate both a safe dose with, and without, what was once referred to as “special” FQPA safety factors.
This emphasis on the broadness of the inquiry is repeated in the discussion of the statutory consideration related to the completeness of the toxicity database. According to EPA, this consideration should not be narrowly focused on EPA's existing database requirements. Rather, “the `completeness' inquiry should be a broad one that takes into account all data deficiencies.” (Ref. 10 at 23). At the same time, the guidance stresses that “a determination of the possible need for and size of the database uncertainty factor will necessarily involve an assessment that
With regard to potential pre- and post-natal toxicity, the policy emphasizes that evaluation of this consideration cannot be divorced from the existing process for choosing levels of concern (i.e., RfDs, PADs, and target MOEs). Thus, EPA instructs risk assessors to evaluate the concern with data showing pre- and post-natal toxicity by considering, among other things, “the degree to which protection for infants and children is provided by the standard approach for deriving RfDs through the application of traditional uncertainty factors.” (Id. at 29). The guidance stresses that “[i]n particular, the risk assessor should consider the protection accorded infants and children by the intraspecies uncertainty factor.” (Id.). EPA notes that the scientific literature as well as the National Academy of Sciences has concluded that the intraspecies factor is generally adequate to protect infants and children; however, the policy points out that certain chemicals may display greater than 10X age-related variability. For this reason, EPA reiterates that “[t]he adequacy of the standard intraspecies factor to address the potential for greater sensitivity or susceptibility of children should be considered in the context of evidence on potential pre- and post-natal toxicity as discussed below.” (Id.;
The discussion on the completeness of the exposure database focuses on whether the various approaches EPA uses to assess exposure are likely to understate it. Risk assessors are to evaluate whether their assessments “have addressed all significant exposure routes” and whether “there may be uncertainty about whether OPP's approach to estimating exposure for a particular use pattern, pathway, or aggregate exposure is sufficiently health protective.” (Id. at 48).
Dichlorvos is a chlorinated organophosphate pesticide that inhibits plasma, red blood cell (RBC), and brain cholinesterase in a variety of species. (Ref. 3 at 122-123). Cholinesterase inhibition is a disruption of the normal process in the body by which the nervous system chemically communicates with muscles and glands. Although cholinesterase inhibition in the nervous system is not itself regarded as a direct adverse effect, it is “generally accepted as a key component of the mechanism of toxicity leading to adverse cholinergic effects.” (Ref. 27 at 25; see 73 FR 42688-42689). Inhibition of blood cholinesterase “is not an adverse effect, but may indicate a potential for adverse effects on the nervous system” and thus serves as a “surrogate” for cholinesterase inhibition in the nervous system (Ref. 27 at 28). Subchronic and chronic oral dichlorvos exposures to rats and dogs as well as chronic inhalation dichlorvos exposure to rats resulted in significant decreases in plasma, RBC, and/or brain cholinesterase activity. Repeated, oral subchronic dichlorvos exposures in male humans were associated with statistically and biologically significant decreases in RBC cholinesterase inhibition. These cholinesterase effects occurred at dose levels below levels at which any other adverse effect was seen. Generally, there was no evidence of increased sensitivity to young animals following exposure to dichlorvos. No evidence of increased sensitivity to young animals was seen following
Because inhibition of cholinesterase activity was identified as the most sensitive effect, it was selected as the toxicity endpoint for assessment of risks for all acute and chronic dietary exposures, as well as short-, intermediate-, and long-term (chronic) dermal, inhalation, and incidental oral residential exposures. For each risk assessment scenario, EPA selected a Point of Departure based on either an animal or human study taking into account the duration of the study and the route of exposure used in the study. (Ref. 3 at 130-135). These Points of Departure were used in calculating RfD/PADs and acceptable MOEs. Due to the lack of sensitivity differences between adults and juveniles, the resulting RfD/PADs and acceptable MOEs were designated as applicable to all population subgroups, including infants and children. Animal studies were used in choosing levels of concern for evaluating risk from acute and chronic dietary exposure; acute dermal exposure; and acute and chronic inhalation exposure. A human study (the Gledhill study) was used in evaluating risk from short-term incidental oral exposure; short-, intermediate-, and long-term dermal exposure; and short- and intermediate-term inhalation exposure. All of the studies from which a Point of Departure was selected were conducted in adults
Safety factor determinations used in determining the level of concern for each risk assessment scenario differed based on whether EPA relied on one of several different animal studies or a human study for the Point of Departure for that scenario. For levels of concerns derived from a Point of Departure from an animal study, EPA generally applied a 100X safety factor (10X for interspecies variability and 10X for intraspecies variability). Based on a weight-of-the-evidence evaluation, EPA removed the 10X FQPA safety factor for risk assessments based on an animal study. (See Table 1). EPA's weight-of-the-evidence evaluation concluded that (1) the toxicity database was complete; (2) most of the data indicated no increased sensitivity in the young and the only evidence of increased sensitivity occurred at levels well above the Points of Departure used for establishing the levels of concern; and (3) its estimate of human exposure to dichlorvos was not understated.
For levels of concerns derived from a Point of Departure from the human study, EPA applied a 10X safety factor for intraspecies variability and a 3X FQPA safety factor. (72 FR 68694-68695). No interspecies factor was applied because EPA was not extrapolating a level of concern in humans from a dose in an animal study. The weight-of-the-evidence balance for the FQPA safety factor was slightly different for risk assessments relying on the Gledhill human study for the Point of Departure. In addition to all of the considerations pertaining to the assessments with an animal-derived Point of Departure, the Gledhill-based risk assessments introduced another factor to consider—namely, that the Gledhill study raised a data completeness issue due to the fact that it only identified a LOAEL. This latter factor convinced EPA to retain a portion of the FQPA safety factor when relying on the human study for the Point of Departure. EPA concluded, however, that reliable data supported reduction of the 10X factor to 3X because the effect seen at the LOAEL in that study was so marginal (16 percent RBC cholinesterase inhibition) that a lower dose would have been unlikely to detect any adverse effect. (72 FR 68694-68695; see Table 1).
On June 2, 2006, the NRDC filed a petition with EPA which, among other things, requested that EPA conclude the dichlorvos tolerance reassessment process by August 3, 2006, with a finding that the dichlorvos tolerances do not meet the FFDCA safety standard and issue a final rule by August 3, 2006, revoking all dichlorvos tolerances. NRDC's petition contained dozens of claims as to why dichlorvos' FFDCA tolerances should be revoked. After carefully considering all of NRDC's claims, the public comment received on the petition, and a revised risk assessment EPA conducted in response to the petition, EPA issued an order pursuant to FFDCA section 408(d)(4)(iii) denying the request to revoke dichlorvos' FFDCA tolerances. (72 FR 68662, December 5, 2007).
On February 1, 2008, NRDC filed, pursuant to FFDCA section 408(g)(2), objections to EPA's denial of its tolerance revocation petition and requested a hearing on those objections. NRDC's objections and requests for hearing included two main claims: (1) That EPA has unlawfully failed to retain the full 10X safety factor for the protection of infants and children; and (2) that it was unlawful for EPA to rely on a toxicity study for dichlorvos (the Gledhill study) that was conducted with humans. Because NRDC did not seek judicial review on EPA's substantive conclusions on the latter issue but only challenged EPA's denial of a hearing on the issue, and because the Second Circuit court on review did not reach the hearing issue, the Gledhill study is
NRDC cited several grounds for its assertion that EPA unlawfully lowered the 10X children's safety factor. However, only two of its arguments were later raised in NRDC's judicial challenge to EPA's decision. First, NRDC claimed that EPA lacked adequate data on dichlorvos' potential effects on the endocrine system because EPA had not received data on endocrine effects through the Endocrine Disruptor Screening Program. Second, NRDC argued that EPA's choice of a 3X additional safety factor was based on generic data and “not [ ] on any data specific to DDVP.” (Ref. 1 at 5).
EPA denied both of NRDC's reasons for its objection to the choice of a 3X FQPA factor. EPA rejected NRDC's endocrine data argument on both legal and factual grounds. EPA concluded that the statute gave it broad discretion to determine what data are needed in making a determination on the FQPA safety factor and that nothing in section 408(p), creating the Endocrine Disruptor Screening Program, overrode that broad discretion. As a factual matter, EPA found that it had adequate data on endocrine effects from the existing dichlorvos database. (73 FR 42697-42698).
EPA also rejected NRDC's claim that it relied on wholly generic data, rather than dichlorvos-specific data, in choosing a 3X FQPA factor. NRDC's argument here was that EPA chose 3X because EPA considers 3X to be a half-value of a 10X factor rather than on data pertaining to dichlorvos. In response, EPA noted that its petition denial order had comprehensively restated its basis for its FQPA safety factor decision, and that restatement focused in great detail on the toxicology data for dichlorvos, particularly, the data on the sensitivity of the young. (73 FR 42695). EPA further pointed out that although the statutory considerations underlying the FQPA safety factor generally supported removal of the 10X additional factor, the reason EPA chose to retain a 3X FQPA safety factor for some assessments was directly tied to a deficiency in a dichlorvos study (the Gledhill study) that is critical to those assessments. (Id.). Thus, there was no basis for NRDC's claim that EPA had not relied on dichlorvos-specific data in making its FQPA safety factor decision.
NRDC petitioned the Second Circuit court for review of EPA's denial of certain of its objections and hearing requests. As to its hearing requests, NRDC argued that EPA improperly denied its request for a hearing on statistical and informed consent issues presented by the Gledhill study. As to its objections, NRDC asserted (1) that, as a legal matter, EPA was required to retain the 10X FQPA factor if it did not have data from the Endocrine Disruptor Screening Program; and (2) that EPA's choice of a 3X FQPA factor was arbitrary and capricious because EPA had relied upon “generic assertions that unlawfully fail to take into account any dichlorvos-specific information for infants and children.” (Ref. 28 at 37). NRDC supported the latter argument in the following fashion. First, it argued that EPA chose 3X solely because it was half of 10X. Second, NRDC asserted that EPA's consideration of the Gledhill study did not constitute “dichlorvos-specific information for infants and children” because the Gledhill study was conducted with adults. Third, NRDC dismissed EPA's reliance on dichlorvos developmental studies in animals on the ground that a prior case had held that EPA had not, in that particular case, offered an adequate explanation of how the data on developing animals supported the FQPA factor chosen.
In response, EPA explained that NRDC's focus on EPA's discussion of why 3X is considered half of 10X ignored the central part of EPA's analysis: An assessment of whether the dichlorvos data showed 3X would be safe. EPA responded to the claim of a failure to consider “dichlorvos-specific information for infants and children” by noting that the Gledhill study had not been considered in isolation in the decision on the FQPA safety factor but in the context of “the animal data showing no difference in adult-young sensitivity” because it was “that very data that shows why the Gledhill study is appropriate for the entire population * * *” (Ref. 29 at 63). Further, EPA noted that NRDC's argument that EPA reliance on animal sensitivity data does not justify a choice of 3X contradicted the core of NRDC's claim—that EPA had not considered “dichlorvos-specific information for infants and children.” (Id. at 62).
On review, the Second Circuit court addressed three issues: (1) Was EPA legally compelled to retain the 10X FQPA safety factor in the absence of obtaining data from the Endocrine Disruptor Screening Program; (2) did EPA adequately explain its decision on the FQPA safety factor; and (3) was NRDC entitled to an evidentiary hearing with regard to its claims regarding the alleged statistical and informed consent deficiencies in the Gledhill study.
The court found that, for risk assessments relying on the Gledhill study in deriving the Point of Departure, EPA had provided essentially no explanation with regard to the FQPA safety factor. The court noted that EPA had retained an additional 3X safety factor for these risk assessments but the court concluded that it was EPA's express position that this factor was not based on any evaluation of the risks to infants and children but rather was intended to address the lack of NOAEL in the Gledhill study only. According to the court, “[i]n EPA's IRED and two published orders, EPA consistently