Effective:[See Text Amendments]

United States Code Annotated Currentness

Title 5. Government Organization and Employees (Refs & Annos)

Part I. The Agencies Generally

Chapter 7. Judicial Review (Refs & Annos)

§ 706. Scope of review

To the extent necessary to decision and when presented, the reviewing court shall decide all relevant questions of law, interpret constitutional and statutory provisions, and determine the meaning or applicability of the terms of an agency action. The reviewing court shall--

(1) compel agency action unlawfully withheld or unreasonably delayed; and

(2) hold unlawful and set aside agency action, findings, and conclusions found to be--

(A) arbitrary, capricious, an abuse of discretion, or otherwise not in accordance with law;

(B) contrary to constitutional right, power, privilege, or immunity;

(C) in excess of statutory jurisdiction, authority, or limitations, or short of statutory right;

(D) without observance of procedure required by law;

(E) unsupported by substantial evidence in a case subject to sections 556 and 557 of this title or otherwise reviewed

on the record of an agency hearing provided by statute; or

(F) unwarranted by the facts to the extent that the facts are subject to trial de novo by the reviewing court.

In making the foregoing determinations, the court shall review the whole record or those parts of it cited by a party, and

due account shall be taken of the rule of prejudicial error.

CREDIT(S)

(Pub.L. 89-554, Sept. 6, 1966, 80 Stat. 393.)

HISTORICAL AND STATUTORY NOTES

Revision Notes and Legislative Reports

1966 Acts.

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Effective:[See Notes]

United States Code Annotated Currentness

Title 21. Food and Drugs (Refs & Annos)

Chapter 9. Federal Food, Drug, and Cosmetic Act (Refs & Annos)

Subchapter IV. Food

§ 346a. Tolerances and exemptions for pesticide chemical residues

(a) Requirement for tolerance or exemption

(1) General rule

Except as provided in paragraph (2) or (3), any pesticide chemical residue in or on a food shall be deemed unsafe for the purpose of section 342(a)(2)(B) of this title unless--

(A) a tolerance for such pesticide chemical residue in or on such food is in effect under this section and the

quantity of the residue is within the limits of the tolerance; or

(B) an exemption from the requirement of a tolerance is in effect under this section for the pesticide chemical residue.

For the purposes of this section, the term “food”, when used as a noun without modification, shall mean a

raw agricultural commodity or processed food.

(2) Processed food

Notwithstanding paragraph (1)--

(A) if a tolerance is in effect under this section for a pesticide chemical residue in or on a raw agricultural

commodity, a pesticide chemical residue that is present in or on a processed food because the food is made

from that raw agricultural commodity shall not be considered unsafe within the meaning of section

342(a)(2)(B) of this title despite the lack of a tolerance for the pesticide chemical residue in or on the processed food if the pesticide chemical has been used in or on the raw agricultural commodity in conformity

with a tolerance under this section, such residue in or on the raw agricultural commodity has been removed

to the extent possible in good manufacturing practice, and the concentration of the pesticide chemical

residue in the processed food is not greater than the tolerance prescribed for the pesticide chemical residue

in the raw agricultural commodity; or

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(B) if an exemption for the requirement for a tolerance is in effect under this section for a pesticide chemical

residue in or on a raw agricultural commodity, a pesticide chemical residue that is present in or on a processed food because the food is made from that raw agricultural commodity shall not be considered unsafe

within the meaning of section 342(a)(2)(B) of this title.

(3) Residues of degradation products

If a pesticide chemical residue is present in or on a food because it is a metabolite or other degradation

product of a precursor substance that itself is a pesticide chemical or pesticide chemical residue, such a

residue shall not be considered to be unsafe within the meaning of section 342(a)(2)(B) of this title despite the

lack of a tolerance or exemption from the need for a tolerance for such residue in or on such food if--

(A) the Administrator has not determined that the degradation product is likely to pose any potential health

risk from dietary exposure that is of a different type than, or of a greater significance than, any risk posed by

dietary exposure to the precursor substance;

(B) either--

(i) a tolerance is in effect under this section for residues of the precursor substance in or on the food, and

the combined level of residues of the degradation product and the precursor substance in or on the food is

at or below the stoichiometrically equivalent level that would be permitted by the tolerance if the residue

consisted only of the precursor substance rather than the degradation product; or

(ii) an exemption from the need for a tolerance is in effect under this section for residues of the precursor

substance in or on the food; and

(C) the tolerance or exemption for residues of the precursor substance does not state that it applies only to

particular named substances and does not state that it does not apply to residues of the degradation product.

(4) Effect of tolerance or exemption

While a tolerance or exemption from the requirement for a tolerance is in effect under this section for a pesticide chemical residue with respect to any food, the food shall not by reason of bearing or containing any

amount of such a residue be considered to be adulterated within the meaning of section 342(a)(1) of this title.

(b) Authority and standard for tolerance

(1) Authority

The Administrator may issue regulations establishing, modifying, or revoking a tolerance for a pesticide

chemical residue in or on a food--

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(A) in response to a petition filed under subsection (d) of this section; or

(B) on the Administrator's own initiative under subsection (e) of this section.

As used in this section, the term “modify” shall not mean expanding the tolerance to cover additional foods.

(2) Standard

(A) General rule

(i) Standard

The Administrator may establish or leave in effect a tolerance for a pesticide chemical residue in or on a

food only if the Administrator determines that the tolerance is safe. The Administrator shall modify or revoke a tolerance if the Administrator determines it is not safe.

(ii) Determination of safety

As used in this section, the term “safe”, with respect to a tolerance for a pesticide chemical residue, means

that the Administrator has determined that there is a reasonable certainty that no harm will result from aggregate exposure to the pesticide chemical residue, including all anticipated dietary exposures and all other exposures for which there is reliable information.

(iii) Rule of construction

With respect to a tolerance, a pesticide chemical residue meeting the standard under clause (i) is not an

eligible pesticide chemical residue for purposes of subparagraph (B).

(B) Tolerances for eligible pesticide chemical residues

(i) Definition

As used in this subparagraph, the term “eligible pesticide chemical residue” means a pesticide chemical

residue as to which--

(I) the Administrator is not able to identify a level of exposure to the residue at which the residue will

not cause or contribute to a known or anticipated harm to human health (referred to in this section as a

“nonthreshold effect”);

(II) the lifetime risk of experiencing the nonthreshold effect is appropriately assessed by quantitative

risk assessment; and

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(III) with regard to any known or anticipated harm to human health for which the Administrator is able

to identify a level at which the residue will not cause such harm (referred to in this section as a

“threshold effect”), the Administrator determines that the level of aggregate exposure is safe.

(ii) Determination of tolerance

Notwithstanding subparagraph (A)(i), a tolerance for an eligible pesticide chemical residue may be left in

effect or modified under this subparagraph if--

(I) at least one of the conditions described in clause (iii) is met; and

(II) both of the conditions described in clause (iv) are met.

(iii) Conditions regarding use

For purposes of clause (ii), the conditions described in this clause with respect to a tolerance for an eligible pesticide chemical residue are the following:

(I) Use of the pesticide chemical that produces the residue protects consumers from adverse effects on

health that would pose a greater risk than the dietary risk from the residue.

(II) Use of the pesticide chemical that produces the residue is necessary to avoid a significant disruption in domestic production of an adequate, wholesome, and economical food supply.

(iv) Conditions regarding risk

For purposes of clause (ii), the conditions described in this clause with respect to a tolerance for an eligible pesticide chemical residue are the following:

(I) The yearly risk associated with the nonthreshold effect from aggregate exposure to the residue does

not exceed 10 times the yearly risk that would be allowed under subparagraph (A) for such effect.

(II) The tolerance is limited so as to ensure that the risk over a lifetime associated with the nonthreshold

effect from aggregate exposure to the residue is not greater than twice the lifetime risk that would be allowed under subparagraph (A) for such effect.

(v) Review

Five years after the date on which the Administrator makes a determination to leave in effect or modify a

tolerance under this subparagraph, and thereafter as the Administrator deems appropriate, the Administrator shall determine, after notice and opportunity for comment, whether it has been demonstrated to the

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Administrator that a condition described in clause (iii)(I) or clause (iii)(II) continues to exist with respect

to the tolerance and that the yearly and lifetime risks from aggregate exposure to such residue continue to

comply with the limits specified in clause (iv). If the Administrator determines by such date that such

demonstration has not been made, the Administrator shall, not later than 180 days after the date of such

determination, issue a regulation under subsection (e)(1) of this section to modify or revoke the tolerance.

(vi) Infants and children

Any tolerance under this subparagraph shall meet the requirements of subparagraph (C).

(C) Exposure of infants and children

In establishing, modifying, leaving in effect, or revoking a tolerance or exemption for a pesticide chemical

residue, the Administrator--

(i) shall assess the risk of the pesticide chemical residue based on--

(I) available information about consumption patterns among infants and children that are likely to result

in disproportionately high consumption of foods containing or bearing such residue among infants and

children in comparison to the general population;

(II) available information concerning the special susceptibility of infants and children to the pesticide

chemical residues, including neurological differences between infants and children and adults, and effects of in utero exposure to pesticide chemicals; and

(III) available information concerning the cumulative effects on infants and children of such residues

and other substances that have a common mechanism of toxicity; and

(ii) shall--

(I) ensure that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to the pesticide chemical residue; and

(II) publish a specific determination regarding the safety of the pesticide chemical residue for infants

and children.

The Secretary of Health and Human Services and the Secretary of Agriculture, in consultation with the

Administrator, shall conduct surveys to document dietary exposure to pesticides among infants and

children. In the case of threshold effects, for purposes of clause (ii)(I) an additional tenfold margin of

safety for the pesticide chemical residue and other sources of exposure shall be applied for infants and

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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. Notwithstanding such requirement for an additional margin of safety, the Administrator may 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.

(D) Factors

In establishing, modifying, leaving in effect, or revoking a tolerance or exemption for a pesticide chemical

residue, the Administrator shall consider, among other relevant factors--

(i) the validity, completeness, and reliability of the available data from studies of the pesticide chemical

and pesticide chemical residue;

(ii) the nature of any toxic effect shown to be caused by the pesticide chemical or pesticide chemical

residue in such studies;

(iii) available information concerning the relationship of the results of such studies to human risk;

(iv) available information concerning the dietary consumption patterns of consumers (and major identifiable subgroups of consumers);

(v) available information concerning the cumulative effects of such residues and other substances that

have a common mechanism of toxicity;

(vi) available information concerning the aggregate exposure levels of consumers (and major identifiable

subgroups of consumers) to the pesticide chemical residue and to other related substances, including dietary exposure under the tolerance and all other tolerances in effect for the pesticide chemical residue, and

exposure from other non-occupational sources;

(vii) available information concerning the variability of the sensitivities of major identifiable subgroups of

consumers;

(viii) such information as the Administrator may require on whether the pesticide chemical may have an

effect in humans that is similar to an effect produced by a naturally occurring estrogen or other endocrine

effects; and

(ix) safety factors which in the opinion of experts qualified by scientific training and experience to evaluate the safety of food additives are generally recognized as appropriate for the use of animal experimentation data.

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(E) Data and information regarding anticipated and actual residue levels

(i) Authority

In establishing, modifying, leaving in effect, or revoking a tolerance for a pesticide chemical residue, the

Administrator may consider available data and information on the anticipated residue levels of the pesticide chemical in or on food and the actual residue levels of the pesticide chemical that have been measured in food, including residue data collected by the Food and Drug Administration.

(ii) Requirement

If the Administrator relies on anticipated or actual residue levels in establishing, modifying, or leaving in

effect a tolerance, the Administrator shall pursuant to subsection (f)(1) of this section require that data be

provided five years after the date on which the tolerance is established, modified, or left in effect, and

thereafter as the Administrator deems appropriate, demonstrating that such residue levels are not above

the levels so relied on. If such data are not so provided, or if the data do not demonstrate that the residue

levels are not above the levels so relied on, the Administrator shall, not later than 180 days after the date

on which the data were required to be provided, issue a regulation under subsection (e)(1) of this section,

or an order under subsection (f)(2) of this section, as appropriate, to modify or revoke the tolerance.

(F) Percent of food actually treated

In establishing, modifying, leaving in effect, or revoking a tolerance for a pesticide chemical residue, the

Administrator may, when assessing chronic dietary risk, consider available data and information on the percent of food actually treated with the pesticide chemical (including aggregate pesticide use data collected by

the Department of Agriculture) only if the Administrator--

(i) finds that the data are reliable and provide a valid basis to show what percentage of the food derived

from such crop is likely to contain such pesticide chemical residue;

(ii) finds that the exposure estimate does not understate exposure for any significant subpopulation group;

(iii) finds that, if data are available on pesticide use and consumption of food in a particular area, the population in such area is not dietarily exposed to residues above those estimated by the Administrator; and

(iv) provides for the periodic reevaluation of the estimate of anticipated dietary exposure.

(3) Detection methods

(A) General rule

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al method for detecting and measuring the levels of the pesticide chemical residue in or on the food.

(B) Detection limit

A tolerance for a pesticide chemical residue in or on a food shall not be established at or modified to a level

lower than the limit of detection of the method for detecting and measuring the pesticide chemical residue

specified by the Administrator under subparagraph (A).

(4) International standards

In establishing a tolerance for a pesticide chemical residue in or on a food, the Administrator shall determine

whether a maximum residue level for the pesticide chemical has been established by the Codex Alimentarius

Commission. If a Codex maximum residue level has been established for the pesticide chemical and the Administrator does not propose to adopt the Codex level, the Administrator shall publish for public comment a

notice explaining the reasons for departing from the Codex level.

(c) Authority and standard for exemptions

(1) Authority

The Administrator may issue a regulation establishing, modifying, or revoking an exemption from the requirement for a tolerance for a pesticide chemical residue in or on food--

(A) in response to a petition filed under subsection (d) of this section; or

(B) on the Administrator's initiative under subsection (e) of this section.

(2) Standard

(A) General rule

(i) Standard

The Administrator may establish or leave in effect an exemption from the requirement for a tolerance for

a pesticide chemical residue in or on food only if the Administrator determines that the exemption is safe.

The Administrator shall modify or revoke an exemption if the Administrator determines it is not safe.

(ii) Determination of safety

The term “safe”, with respect to an exemption for a pesticide chemical residue, means that the Administrator has determined that there is a reasonable certainty that no harm will result from aggregate exposure

to the pesticide chemical residue, including all anticipated dietary exposures and all other exposures for

which there is reliable information.

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(B) Factors

In making a determination under this paragraph, the Administrator shall take into account, among other relevant considerations, the considerations set forth in subparagraphs (C) and (D) of subsection (b)(2) of this

section.

(3) Limitation

An exemption from the requirement for a tolerance for a pesticide chemical residue in or on food shall not be

established or modified by the Administrator unless the Administrator determines, after consultation with the

Secretary--

(A) that there is a practical method for detecting and measuring the levels of such pesticide chemical residue

in or on food; or

(B) that there is no need for such a method, and states the reasons for such determination in issuing the regulation establishing or modifying the exemption.

(d) Petition for tolerance or exemption

(1) Petitions and petitioners

Any person may file with the Administrator a petition proposing the issuance of a regulation--

(A) establishing, modifying, or revoking a tolerance for a pesticide chemical residue in or on a food; or

(B) establishing, modifying, or revoking an exemption from the requirement of a tolerance for such a

residue.

(2) Petition contents

(A) Establishment

A petition under paragraph (1) to establish a tolerance or exemption for a pesticide chemical residue shall be

supported by such data and information as are specified in regulations issued by the Administrator, including--

(i)(I) an informative summary of the petition and of the data, information, and arguments submitted or

cited in support of the petition; and

(II) a statement that the petitioner agrees that such summary or any information it contains may be published as a part of the notice of filing of the petition to be published under this subsection and as part of a

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proposed or final regulation issued under this section;

(ii) the name, chemical identity, and composition of the pesticide chemical residue and of the pesticide

chemical that produces the residue;

(iii) data showing the recommended amount, frequency, method, and time of application of that pesticide

chemical;

(iv) full reports of tests and investigations made with respect to the safety of the pesticide chemical, including full information as to the methods and controls used in conducting those tests and investigations;

(v) full reports of tests and investigations made with respect to the nature and amount of the pesticide

chemical residue that is likely to remain in or on the food, including a description of the analytical methods used;

(vi) a practical method for detecting and measuring the levels of the pesticide chemical residue in or on

the food, or for exemptions, a statement why such a method is not needed;

(vii) a proposed tolerance for the pesticide chemical residue, if a tolerance is proposed;

(viii) if the petition relates to a tolerance for a processed food, reports of investigations conducted using

the processing method(s) used to produce that food;

(ix) such information as the Administrator may require to make the determination under subsection

(b)(2)(C) of this section;

(x) such information as the Administrator may require on whether the pesticide chemical may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen or other endocrine

effects;

(xi) information regarding exposure to the pesticide chemical residue due to any tolerance or exemption

already granted for such residue;

(xii) practical methods for removing any amount of the residue that would exceed any proposed tolerance;

and

(xiii) such other data and information as the Administrator requires by regulation to support the petition.

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If information or data required by this subparagraph is available to the Administrator, the person submitting the petition may cite the availability of the information or data in lieu of submitting it. The Administrator may require a petition to be accompanied by samples of the pesticide chemical with respect

to which the petition is filed.

(B) Modification or revocation

The Administrator may by regulation establish the requirements for information and data to support a petition to modify or revoke a tolerance or to modify or revoke an exemption from the requirement for a tolerance.

(3) Notice

A notice of the filing of a petition that the Administrator determines has met the requirements of paragraph (2)

shall be published by the Administrator within 30 days after such determination. The notice shall announce

the availability of a description of the analytical methods available to the Administrator for the detection and

measurement of the pesticide chemical residue with respect to which the petition is filed or shall set forth the

petitioner's statement of why such a method is not needed. The notice shall include the summary required by

paragraph (2)(A)(i)(I).

(4) Actions by the Administrator

(A) In general

The Administrator shall, after giving due consideration to a petition filed under paragraph (1) and any other

information available to the Administrator--

(i) issue a final regulation (which may vary from that sought by the petition) establishing, modifying, or

revoking a tolerance for the pesticide chemical residue or an exemption of the pesticide chemical residue

from the requirement of a tolerance (which final regulation shall be issued without further notice and

without further period for public comment);

(ii) issue a proposed regulation under subsection (e) of this section, and thereafter issue a final regulation

under such subsection; or

(iii) issue an order denying the petition.

(B) Priorities

The Administrator shall give priority to petitions for the establishment or modification of a tolerance or exemption for a pesticide chemical residue that appears to pose a significantly lower risk to human health

from dietary exposure than pesticide chemical residues that have tolerances in effect for the same or similar

uses.

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(C) Expedited review of certain petitions

(i) Date certain for review

If a person files a complete petition with the Administrator proposing the issuance of a regulation establishing a tolerance or exemption for a pesticide chemical residue that presents a lower risk to human

health than a pesticide chemical residue for which a tolerance has been left in effect or modified under

subsection (b)(2)(B) of this section, the Administrator shall complete action on such petition under this

paragraph within 1 year.

(ii) Required determinations

If the Administrator issues a final regulation establishing a tolerance or exemption for a safer pesticide

chemical residue under clause (i), the Administrator shall, not later than 180 days after the date on which

the regulation is issued, determine whether a condition described in subclause (I) or (II) of subsection

(b)(2)(B)(iii) of this section continues to exist with respect to a tolerance that has been left in effect or

modified under subsection (b)(2)(B) of this section. If such condition does not continue to exist, the Administrator shall, not later than 180 days after the date on which the determination under the preceding

sentence is made, issue a regulation under subsection (e)(1) of this section to modify or revoke the tolerance.

(e) Action on Administrator's own initiative

(1) General rule

The Administrator may issue a regulation--

(A) establishing, modifying, suspending under subsection (l)(3) of this section, or revoking a tolerance for a

pesticide chemical or a pesticide chemical residue;

(B) establishing, modifying, suspending under subsection (l)(3) of this section, or revoking an exemption of

a pesticide chemical residue from the requirement of a tolerance; or

(C) establishing general procedures and requirements to implement this section.

(2) Notice

Before issuing a final regulation under paragraph (1), the Administrator shall issue a notice of proposed rulemaking and provide a period of not less than 60 days for public comment on the proposed regulation, except

that a shorter period for comment may be provided if the Administrator for good cause finds that it would be

in the public interest to do so and states the reasons for the finding in the notice of proposed rulemaking.

(f) Special data requirements

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(1) Requiring submission of additional data

If the Administrator determines that additional data or information are reasonably required to support the continuation of a tolerance or exemption that is in effect under this section for a pesticide chemical residue on a

food, the Administrator shall--

(A) issue a notice requiring the person holding the pesticide registrations associated with such tolerance or

exemption to submit the data or information under section 3(c)(2)(B) of the Federal Insecticide, Fungicide,

and Rodenticide Act [7 U.S.C.A. § 136a(c)(2)(B)];

(B) issue a rule requiring that testing be conducted on a substance or mixture under section 4 of the Toxic

Substances Control Act [15 U.S.C.A. § 2603]; or

(C) publish in the Federal Register, after first providing notice and an opportunity for comment of not less

than 60 days' duration, an order--

(i) requiring the submission to the Administrator by one or more interested persons of a notice identifying

the person or persons who will submit the required data and information;

(ii) describing the type of data and information required to be submitted to the Administrator and stating

why the data and information could not be obtained under the authority of section 3(c)(2)(B) of the Federal Insecticide, Fungicide, and Rodenticide Act [7 U.S.C.A. § 136a(c)(2)(B)] or section 4 of the Toxic Substances Control Act [15 U.S.C.A. § 2603];

(iii) describing the reports of the Administrator required to be prepared during and after the collection of

the data and information;

(iv) requiring the submission to the Administrator of the data, information, and reports referred to in

clauses (ii) and (iii); and

(v) establishing dates by which the submissions described in clauses (i) and (iv) must be made.

The Administrator may under subparagraph (C) revise any such order to correct an error. The Administrator may under this paragraph require data or information pertaining to whether the pesticide chemical

may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen or

other endocrine effects.

(2) Noncompliance

If a submission required by a notice issued in accordance with paragraph (1)(A), a rule issued under paragraph

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(1)(B), or an order issued under paragraph (1)(C) is not made by the time specified in such notice, rule, or order, the Administrator may by order published in the Federal Register modify or revoke the tolerance or exemption in question. In any review of such an order under subsection (g)(2) of this section, the only material

issue shall be whether a submission required under paragraph (1) was not made by the time specified.

(g) Effective date, objections, hearings, and administrative review

(1) Effective date

A regulation or order issued under subsection (d)(4), (e)(1), or (f)(2) of this section shall take effect upon publication unless the regulation or order specifies otherwise. The Administrator may stay the effectiveness of the

regulation or order if, after issuance of such regulation or order, objections are filed with respect to such regulation or order pursuant to paragraph (2).

(2) Further proceedings

(A) Objections

Within 60 days after a regulation or order is issued under subsection (d)(4), (e)(1)(A), (e)(1)(B), (f)(2),

(n)(3), or (n)(5)(C) of this section, any person may file objections thereto with the Administrator, specifying

with particularity the provisions of the regulation or order deemed objectionable and stating reasonable

grounds therefor. If the regulation or order was issued in response to a petition under subsection (d)(1) of

this section, a copy of each objection filed by a person other than the petitioner shall be served by the Administrator on the petitioner.

(B) Hearing

An objection may include a request for a public evidentiary hearing upon the objection. The Administrator

shall, upon the initiative of the Administrator or upon the request of an interested person and after due notice, 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.

The presiding officer in such a hearing may authorize a party to obtain discovery from other persons and

may upon a showing of good cause made by a party issue a subpoena to compel testimony or production of

documents from any person. The presiding officer shall be governed by the Federal Rules of Civil Procedure in making any order for the protection of the witness or the content of documents produced and shall order the payment of reasonable fees and expenses as a condition to requiring testimony of the witness. On

contest, such a subpoena may be enforced by a Federal district court.

(C) Final decision

As soon as practicable after receiving the arguments of the parties, the Administrator shall issue an order

stating the action taken upon each such objection and setting forth any revision to the regulation or prior order that the Administrator has found to be warranted. If a hearing was held under subparagraph (B), such order and any revision to the regulation or prior order shall, with respect to questions of fact at issue in the

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hearing, be based only on substantial evidence of record at such hearing, and shall set forth in detail the

findings of facts and the conclusions of law or policy upon which the order or regulation is based.

(h) Judicial review

(1) Petition

In a case of actual controversy as to the validity of any regulation issued under subsection (e)(1)(C) of this

section, or any order issued under subsection (f)(1)(C) or (g)(2)(C) of this section, or any regulation that is the

subject of such an order, any person who will be adversely affected by such order or regulation may obtain judicial review by filing in the United States Court of Appeals for the circuit wherein that person resides or has

its principal place of business, or in the United States Court of Appeals for the District of Columbia Circuit,

within 60 days after publication of such order or regulation, a petition praying that the order or regulation be

set aside in whole or in part.

(2) Record and jurisdiction

A copy of the petition under paragraph (1) shall be forthwith transmitted by the clerk of the court to the Administrator, or any officer designated by the Administrator for that purpose, and thereupon the Administrator

shall file in the court the record of the proceedings on which the Administrator based the order or regulation,

as provided in section 2112 of Title 28. Upon the filing of such a petition, the court shall have exclusive jurisdiction to affirm or set aside the order or regulation complained of in whole or in part. As to orders issued following a public evidentiary hearing, the findings of the Administrator with respect to questions of fact shall be

sustained only if supported by substantial evidence when considered on the record as a whole.

(3) Additional evidence

If a party applies to the court for leave to adduce additional evidence and shows to the satisfaction of the court

that the additional evidence is material and that there were reasonable grounds for the failure to adduce the

evidence in the proceeding before the Administrator, the court may order that the additional evidence (and

evidence in rebuttal thereof) shall be taken before the Administrator in the manner and upon the terms and

conditions the court deems proper. The Administrator may modify prior findings as to the facts by reason of

the additional evidence so taken and may modify the order or regulation accordingly. The Administrator shall

file with the court any such modified finding, order, or regulation.

(4) Final judgment; Supreme Court review

The judgment of the court affirming or setting aside, in whole or in part, any regulation or any order and any

regulation which is the subject of such an order shall be final, subject to review by the Supreme Court of the

United States as provided in section 1254 of Title 28. The commencement of proceedings under this subsection shall not, unless specifically ordered by the court to the contrary, operate as a stay of a regulation or order.

(5) Application

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Any issue as to which review is or was obtainable under this subsection shall not be the subject of judicial review under any other provision of law.

(i) Confidentiality and use of data

(1) General rule

Data and information that are or have been submitted to the Administrator under this section or section 348 of

this title in support of a tolerance or an exemption from a tolerance shall be entitled to confidential treatment

for reasons of business confidentiality and to exclusive use and data compensation to the same extent provided

by sections 3 and 10 of the Federal Insecticide, Fungicide, and Rodenticide Act [7 U.S.C.A. §§ 136a and

136h].

(2) Exceptions

(A) In general

Data and information that are entitled to confidential treatment under paragraph (1) may be disclosed, under

such security requirements as the Administrator may provide by regulation, to--

(i) employees of the United States authorized by the Administrator to examine such data and information

in the carrying out of their official duties under this chapter or other Federal statutes intended to protect

the public health; or

(ii) contractors with the United States authorized by the Administrator to examine such data and information in the carrying out of contracts under this chapter or such statutes.

(B) Congress

This subsection does not authorize the withholding of data or information from either House of Congress or

from, to the extent of matter within its jurisdiction, any committee or subcommittee of such committee or

any joint committee of Congress or any subcommittee of such joint committee.

(3) Summaries

Notwithstanding any provision of this subsection or other law, the Administrator may publish the informative

summary required by subsection (d)(2)(A)(i) of this section and may, in issuing a proposed or final regulation

or order under this section, publish an informative summary of the data relating to the regulation or order.

(j) Status of previously issued regulations

(1) Regulations under section 346

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Regulations affecting pesticide chemical residues in or on raw agricultural commodities promulgated, in accordance with section 371(e) of this title, under the authority of section 346(a) of this title upon the basis of

public hearings instituted before January 1, 1953, shall be deemed to be regulations issued under this section

and shall be subject to modification or revocation under subsections (d) and (e) of this section, and shall be

subject to review under subsection (q) of this section.

(2) Regulations under section 348

Regulations that established tolerances for substances that are pesticide chemical residues in or on processed

food, or that otherwise stated the conditions under which such pesticide chemicals could be safely used, and

that were issued under section 348 of this title on or before August 3, 1996, shall be deemed to be regulations

issued under this section and shall be subject to modification or revocation under subsection (d) or (e) of this

section, and shall be subject to review under subsection (q) of this section.

(3) Regulations under section 346a

Regulations that established tolerances or exemptions under this section that were issued on or before August

3, 1996, shall remain in effect unless modified or revoked under subsection (d) or (e) of this section, and shall

be subject to review under subsection (q) of this section.

(4) Certain substances

With respect to a substance that is not included in the definition of the term “pesticide chemical” under section

321(q)(1) of this title but was so included on the day before October 30, 1998, the following applies as of October 30, 1998:

(A) Notwithstanding paragraph (2), any regulation applying to the use of the substance that was in effect on

the day before October 30, 1998, and was on such day deemed in such paragraph to have been issued under

this section, shall be considered to have been issued under section 348 of this title.

(B) Notwithstanding paragraph (3), any regulation applying to the use of the substance that was in effect on

such day and was issued under this section (including any such regulation issued before August 3, 1996) is

deemed to have been issued under section 348 of this title.

(k) Transitional provision

If, on the day before August 3, 1996, a substance that is a pesticide chemical was, with respect to a particular

pesticidal use of the substance and any resulting pesticide chemical residue in or on a particular food--

(1) regarded by the Administrator or the Secretary as generally recognized as safe for use within the meaning

of the provisions of subsection (a) of this section or section 321(s) of this title as then in effect; or

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(2) regarded by the Secretary as a substance described by section 321(s)(4) of this title;

such a pesticide chemical residue shall be regarded as exempt from the requirement for a tolerance, as of August

3, 1996. The Administrator shall by regulation indicate which substances are described by this subsection. Any

exemption under this subsection may be modified or revoked as if it had been issued under subsection (c) of this

section.

(l) Harmonization with action under other laws

(1) Coordination with FIFRA

To the extent practicable and consistent with the review deadlines in subsection (q) of this section, in issuing a

final rule under this subsection that suspends or revokes a tolerance or exemption for a pesticide chemical

residue in or on food, the Administrator shall coordinate such action with any related necessary action under

the Federal Insecticide, Fungicide, and Rodenticide Act.

(2) Revocation of tolerance or exemption following cancellation of associated registrations

If the Administrator, acting under the Federal Insecticide, Fungicide, and Rodenticide Act [7 U.S.C.A. § 136

et seq.], cancels the registration of each pesticide that contains a particular pesticide chemical and that is

labeled for use on a particular food, or requires that the registration of each such pesticide be modified to prohibit its use in connection with the production, storage, or transportation of such food, due in whole or in part

to dietary risks to humans posed by residues of that pesticide chemical on that food, the Administrator shall

revoke any tolerance or exemption that allows the presence of the pesticide chemical, or any pesticide chemical residue that results from its use, in or on that food. Subsection (e) of this section shall apply to actions taken

under this paragraph. A revocation under this paragraph shall become effective not later than 180 days after--

(A) the date by which each such cancellation of a registration has become effective; or

(B) the date on which the use of the canceled pesticide becomes unlawful under the terms of the cancellation, whichever is later.

(3) Suspension of tolerance or exemption following suspension of associated registrations

(A) Suspension

If the Administrator, acting under the Federal Insecticide, Fungicide, and Rodenticide Act, suspends the use

of each registered pesticide that contains a particular pesticide chemical and that is labeled for use on a particular food, due in whole or in part to dietary risks to humans posed by residues of that pesticide chemical

on that food, the Administrator shall suspend any tolerance or exemption that allows the presence of the

pesticide chemical, or any pesticide chemical residue that results from its use, in or on that food. Subsection

(e) of this section shall apply to actions taken under this paragraph. A suspension under this paragraph shall

become effective not later than 60 days after the date by which each such suspension of use has become ef21 U.S.C.A. § 346a Page 18

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fective.

(B) Effect of suspension

The suspension of a tolerance or exemption under subparagraph (A) shall be effective as long as the use of

each associated registration of a pesticide is suspended under the Federal Insecticide, Fungicide, and Rodenticide Act. While a suspension of a tolerance or exemption is effective the tolerance or exemption shall

not be considered to be in effect. If the suspension of use of the pesticide under that Act is terminated, leaving the registration of the pesticide for such use in effect under that Act, the Administrator shall rescind any

associated suspension of tolerance or exemption.

(4) Tolerances for unavoidable residues

In connection with action taken under paragraph (2) or (3), or with respect to pesticides whose registrations

were suspended or canceled prior to August 3, 1996, under the Federal Insecticide, Fungicide, and Rodenticide Act, if the Administrator determines that a residue of the canceled or suspended pesticide chemical will

unavoidably persist in the environment and thereby be present in or on a food, the Administrator may establish

a tolerance for the pesticide chemical residue. In establishing such a tolerance, the Administrator shall take into account both the factors set forth in subsection (b)(2) of this section and the unavoidability of the residue.

Subsection (e) of this section shall apply to the establishment of such tolerance. The Administrator shall review any such tolerance periodically and modify it as necessary so that it allows no greater level of the pesticide chemical residue than is unavoidable.

(5) Pesticide residues resulting from lawful application of pesticide

Notwithstanding any other provision of this chapter, if a tolerance or exemption for a pesticide chemical

residue in or on a food has been revoked, suspended, or modified under this section, an article of that food

shall not be deemed unsafe solely because of the presence of such pesticide chemical residue in or on such

food if it is shown to the satisfaction of the Secretary that--

(A) the residue is present as the result of an application or use of a pesticide at a time and in a manner that

was lawful under the Federal Insecticide, Fungicide, and Rodenticide Act; and

(B) the residue does not exceed a level that was authorized at the time of that application or use to be

present on the food under a tolerance, exemption, food additive regulation, or other sanction then in effect

under this chapter;

unless, in the case of any tolerance or exemption revoked, suspended, or modified under this subsection or

subsection (d) or (e) of this section, the Administrator has issued a determination that consumption of the

legally treated food during the period of its likely availability in commerce will pose an unreasonable dietary risk.

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(6) Tolerance for use of pesticides under an emergency exemption

If the Administrator grants an exemption under section 18 of the Federal Insecticide, Fungicide, and Rodenticide Act (7 U.S.C. 136p) for a pesticide chemical, the Administrator shall establish a tolerance or exemption

from the requirement for a tolerance for the pesticide chemical residue. Such a tolerance or exemption from a

tolerance shall have an expiration date. The Administrator may establish such a tolerance or exemption

without providing notice or a period for comment on the tolerance or exemption. The Administrator shall promulgate regulations within 365 days after August 3, 1996, governing the establishment of tolerances and exemptions under this paragraph. Such regulations shall be consistent with the safety standard under subsections

(b)(2) and (c)(2) of this section and with section 18 of the Federal Insecticide, Fungicide, and Rodenticide

Act.

(m) Fees

(1) Amount

The Administrator shall by regulation require the payment of such fees as will in the aggregate, in the judgment of the Administrator, be sufficient over a reasonable term to provide, equip, and maintain an adequate

service for the performance of the Administrator's functions under this section. Under the regulations, the performance of the Administrator's services or other functions under this section, including--

(A) the acceptance for filing of a petition submitted under subsection (d) of this section;

(B) establishing, modifying, leaving in effect, or revoking a tolerance or establishing, modifying, leaving in

effect, or revoking an exemption from the requirement for a tolerance under this section;

(C) the acceptance for filing of objections under subsection (g) of this section; or

(D) the certification and filing in court of a transcript of the proceedings and the record under subsection (h)

of this section;

may be conditioned upon the payment of such fees. The regulations may further provide for waiver or refund of fees in whole or in part when in the judgment of the Administrator such a waiver or refund is equitable and not contrary to the purposes of this subsection.

(2) Deposit

All fees collected under paragraph (1) shall be deposited in the Reregistration and Expedited Processing Fund

created by section 4(k) of the Federal Insecticide, Fungicide, and Rodenticide Act [7 U.S.C.A. § 136a-1(k)].

Such fees shall be available to the Administrator, without fiscal year limitation, for the performance of the Administrator's services or functions as specified in paragraph (1).

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(3) Prohibition

During the period beginning on the effective date of the Pesticide Registration Improvement Renewal Act and

ending on September 30, 2012, the Administrator shall not collect any tolerance fees under paragraph (1).

(n) National uniformity of tolerances

(1) “Qualifying pesticide chemical residue” defined

For purposes of this subsection, the term “qualifying pesticide chemical residue” means a pesticide chemical

residue resulting from the use, in production, processing, or storage of a food, of a pesticide chemical that is

an active ingredient and that--

(A) was first approved for such use in a registration of a pesticide issued under section 3(c)(5) of the Federal

Insecticide, Fungicide, and Rodenticide Act [7 U.S.C.A. § 1365(c)(5)] on or after April 25, 1985, on the

basis of data determined by the Administrator to meet all applicable requirements for data prescribed by

regulations in effect under that Act [7 U.S.C.A. § 136 et seq.] on April 25, 1985; or

(B) was approved for such use in a reregistration eligibility determination issued under section 4(g) of that

Act [7 U.S.C.A. § 136a-1(g)] on or after August 3, 1996.

(2) Qualifying Federal determination

For purposes of this subsection, the term “qualifying Federal determination” means a tolerance or exemption

from the requirement for a tolerance for a qualifying pesticide chemical residue that--

(A) is issued under this section after August 3, 1996, and determined by the Administrator to meet the

standard under subsection (b)(2)(A) (in the case of a tolerance) or (c)(2) (in the case of an exemption) of

this section; or

(B)(i) pursuant to subsection (j) of this section is remaining in effect or is deemed to have been issued under

this section, or is regarded under subsection (k) of this section as exempt from the requirement for a tolerance; and

(ii) is determined by the Administrator to meet the standard under subsection (b)(2)(A) (in the case of a tolerance) or (c)(2) (in the case of an exemption) of this section.

(3) Limitation

The Administrator may make the determination described in paragraph (2)(B)(ii) only by issuing a rule in accordance with the procedure set forth in subsection (d) or (e) of this section and only if the Administrator issues a proposed rule and allows a period of not less than 30 days for comment on the proposed rule. Any such

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rule shall be reviewable in accordance with subsections (g) and (h) of this section.

(4) State authority

Except as provided in paragraphs (5), (6), and (8) no State or political subdivision may establish or enforce

any regulatory limit on a qualifying pesticide chemical residue in or on any food if a qualifying Federal determination applies to the presence of such pesticide chemical residue in or on such food, unless such State

regulatory limit is identical to such qualifying Federal determination. A State or political subdivision shall be

deemed to establish or enforce a regulatory limit on a pesticide chemical residue in or on a food if it purports

to prohibit or penalize the production, processing, shipping, or other handling of a food because it contains a

pesticide residue (in excess of a prescribed limit).

(5) Petition procedure

(A) In general

Any State may petition the Administrator for authorization to establish in such State a regulatory limit on a

qualifying pesticide chemical residue in or on any food that is not identical to the qualifying Federal determination applicable to such qualifying pesticide chemical residue.

(B) Petition requirements

Any petition under subparagraph (A) shall--

(i) satisfy any requirements prescribed, by rule, by the Administrator; and

(ii) be supported by scientific data about the pesticide chemical residue that is the subject of the petition

or about chemically related pesticide chemical residues, data on the consumption within such State of

food bearing the pesticide chemical residue, and data on exposure of humans within such State to the

pesticide chemical residue.

(C) Authorization

The Administrator may, by order, grant the authorization described in subparagraph (A) if the Administrator

determines that the proposed State regulatory limit--

(i) is justified by compelling local conditions; and

(ii) would not cause any food to be a violation of Federal law.

(D) Treatment

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In lieu of any action authorized under subparagraph (C), the Administrator may treat a petition under this

paragraph as a petition under subsection (d) of this section to modify or revoke a tolerance or an exemption.

If the Administrator determines to treat a petition under this paragraph as a petition under subsection (d) of

this section, the Administrator shall thereafter act on the petition pursuant to subsection (d) of this section.

(E) Review

Any order of the Administrator granting or denying the authorization described in subparagraph (A) shall be

subject to review in the manner described in subsections (g) and (h) of this section.

(6) Urgent petition procedure

Any State petition to the Administrator pursuant to paragraph (5) that demonstrates that consumption of a food

containing such pesticide residue level during the period of the food's likely availability in the State will pose

a significant public health threat from acute exposure shall be considered an urgent petition. If an order by the

Administrator to grant or deny the requested authorization in an urgent petition is not made within 30 days of

receipt of the petition, the petitioning State may establish and enforce a temporary regulatory limit on a qualifying pesticide chemical residue in or on the food. The temporary regulatory limit shall be validated or terminated by the Administrator's final order on the petition.

(7) Residues from lawful application

No State or political subdivision may enforce any regulatory limit on the level of a pesticide chemical residue

that may appear in or on any food if, at the time of the application of the pesticide that resulted in such

residue, the sale of such food with such residue level was lawful under this section and under the law of such

State, unless the State demonstrates that consumption of the food containing such pesticide residue level during the period of the food's likely availability in the State will pose an unreasonable dietary risk to the health

of persons within such State.

(8) Savings

Nothing in this chapter preempts the authority of any State or political subdivision to require that a food containing a pesticide chemical residue bear or be the subject of a warning or other statement relating to the presence of the pesticide chemical residue in or on such food.

(o) Consumer right to know

Not later than 2 years after August 3, 1996, and annually thereafter, the Administrator shall, in consultation with

the Secretary of Agriculture and the Secretary of Health and Human Services, publish in a format understandable to a lay person, and distribute to large retail grocers for public display (in a manner determined by the grocer), the following information, at a minimum:

(1) A discussion of the risks and benefits of pesticide chemical residues in or on food purchased by con21 U.S.C.A. § 346a Page 23

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sumers.

(2) A listing of actions taken under subparagraph (B) of subsection (b)(2) of this section that may result in

pesticide chemical residues in or on food that present a yearly or lifetime risk above the risk allowed under

subparagraph (A) of such subsection, and the food on which the pesticide chemicals producing the residues

are used.

(3) Recommendations to consumers for reducing dietary exposure to pesticide chemical residues in a manner

consistent with maintaining a healthy diet, including a list of food that may reasonably substitute for food listed under paragraph (2).

Nothing in this subsection shall prevent retail grocers from providing additional information.

(p) Estrogenic substances screening program

(1) Development

Not later than 2 years after August 3, 1996, the Administrator shall in consultation with the Secretary of

Health and Human Services develop a screening program, using appropriate validated test systems and other

scientifically relevant information, to determine whether certain substances may have an effect in humans that

is similar to an effect produced by a naturally occurring estrogen, or such other endocrine effect as the Administrator may designate.

(2) Implementation

Not later than 3 years after August 3, 1996, after obtaining public comment and review of the screening program described in paragraph (1) by the scientific advisory panel established under section 25(d) of the Federal

Insecticide, Fungicide, and Rodenticide Act [7 U.S.C.A. § 136w(d)] or the science advisory board established

by section 4365 of Title 42, the Administrator shall implement the program.

(3) Substances

In carrying out the screening program described in paragraph (1), the Administrator--

(A) shall provide for the testing of all pesticide chemicals; and

(B) may provide for the testing of any other substance that may have an effect that is cumulative to an effect

of a pesticide chemical if the Administrator determines that a substantial population may be exposed to such

substance.

(4) Exemption

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Notwithstanding paragraph (3), the Administrator may, by order, exempt from the requirements of this section

a biologic substance or other substance if the Administrator determines that the substance is anticipated not to

produce any effect in humans similar to an effect produced by a naturally occurring estrogen.

(5) Collection of information

(A) In general

The Administrator shall issue an order to a registrant of a substance for which testing is required under this

subsection, or to a person who manufactures or imports a substance for which testing is required under this

subsection, to conduct testing in accordance with the screening program described in paragraph (1), and

submit information obtained from the testing to the Administrator, within a reasonable time period that the

Administrator determines is sufficient for the generation of the information.

(B) Procedures

To the extent practicable the Administrator shall minimize duplicative testing of the same substance for the

same endocrine effect, develop, as appropriate, procedures for fair and equitable sharing of test costs, and

develop, as necessary, procedures for handling of confidential business information.

(C) Failure of registrants to submit information

(i) Suspension

If a registrant of a substance referred to in paragraph (3)(A) fails to comply with an order under subparagraph (A) of this paragraph, the Administrator shall issue a notice of intent to suspend the sale or distribution of the substance by the registrant. Any suspension proposed under this paragraph shall become final

at the end of the 30-day period beginning on the date that the registrant receives the notice of intent to

suspend, unless during that period a person adversely affected by the notice requests a hearing or the Administrator determines that the registrant has complied fully with this paragraph.

(ii) Hearing

If a person requests a hearing under clause (i), the hearing shall be conducted in accordance with section

554 of Title 5. The only matter for resolution at the hearing shall be whether the registrant has failed to

comply with an order under subparagraph (A) of this paragraph. A decision by the Administrator after

completion of a hearing shall be considered to be a final agency action.

(iii) Termination of suspensions

The Administrator shall terminate a suspension under this subparagraph issued with respect to a registrant

if the Administrator determines that the registrant has complied fully with this paragraph.

(D) Noncompliance by other persons

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Any person (other than a registrant) who fails to comply with an order under subparagraph (A) shall be liable for the same penalties and sanctions as are provided under section 16 of the Toxic Substances Control

Act [15 U.S.C.A. § 2615] in the case of a violation referred to in that section. Such penalties and sanctions

shall be assessed and imposed in the same manner as provided in such section 16.

(6) Agency action

In the case of any substance that is found, as a result of testing and evaluation under this section, to have an

endocrine effect on humans, the Administrator shall, as appropriate, take action under such statutory authority

as is available to the Administrator, including consideration under other sections of this chapter, as is necessary to ensure the protection of public health.

(7) Report to Congress

Not later than 4 years after August 3, 1996, the Administrator shall prepare and submit to Congress a report

containing--

(A) the findings of the Administrator resulting from the screening program described in paragraph (1);

(B) recommendations for further testing needed to evaluate the impact on human health of the substances

tested under the screening program; and

(C) recommendations for any further actions (including any action described in paragraph (6)) that the Administrator determines are appropriate based on the findings.

(q) Schedule for review

(1) In general

The Administrator shall review tolerances and exemptions for pesticide chemical residues in effect on the day

before August 3, 1996, as expeditiously as practicable, assuring that--

(A) 33 percent of such tolerances and exemptions are reviewed within 3 years of August 3, 1996;

(B) 66 percent of such tolerances and exemptions are reviewed within 6 years of August 3, 1996; and

(C) 100 percent of such tolerances and exemptions are reviewed within 10 years of August 3, 1996.

In conducting a review of a tolerance or exemption, the Administrator shall determine whether the tolerance

or exemption meets the requirements of subsections [FN1] (b)(2) or (c)(2) of this section and shall, by the

deadline for the review of the tolerance or exemption, issue a regulation under subsection (d)(4) or (e)(1) of

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this section to modify or revoke the tolerance or exemption if the tolerance or exemption does not meet such

requirements.

(2) Priorities

In determining priorities for reviewing tolerances and exemptions under paragraph (1), the Administrator shall

give priority to the review of the tolerances or exemptions that appear to pose the greatest risk to public

health.

(3) Publication of schedule

Not later than 12 months after August 3, 1996, the Administrator shall publish a schedule for review of tolerances and exemptions established prior to August 3, 1996. The determination of priorities for the review of

tolerances and exemptions pursuant to this subsection is not a rulemaking and shall not be subject to judicial

review, except that failure to take final action pursuant to the schedule established by this paragraph shall be

subject to judicial review.

(r) Temporary tolerance or exemption

The Administrator may, upon the request of any person who has obtained an experimental permit for a pesticide

chemical under the Federal Insecticide, Fungicide, and Rodenticide Act [7 U.S.C.A. § 136 et seq.] or upon the

Administrator's own initiative, establish a temporary tolerance or exemption for the pesticide chemical residue

for the uses covered by the permit. Subsections (b)(2), (c)(2), (d), and (e) of this section shall apply to actions

taken under this subsection.

(s) Savings clause

Nothing in this section shall be construed to amend or modify the provisions of the Toxic Substances Control

Act [15 U.S.C.A. § 2601 et seq.] or the Federal Insecticide, Fungicide, and Rodenticide Act [7 U.S.C.A. § 136 et

seq.].

CREDIT(S)

(June 25, 1938, c. 675, § 408, as added July 22, 1954, c. 559, § 3, 68 Stat. 511, and amended Aug. 28, 1958,

Pub.L. 85-791, § 20, 72 Stat. 947; Oct. 30, 1970, Pub.L. 91-515, Title VI, § 601(d)(1), 84 Stat. 1311; 1970 Reorg. Plan No. 3, § 2(a)(4), (8)(ii), eff. Dec. 2, 1970, 35 F.R. 15623, 84 Stat. 2086; Nov. 18, 1971, Pub.L. 92-157,

Title III, § 303(a), 85 Stat. 464; Oct. 21, 1972, Pub.L. 92-516, § 3(3), 86 Stat. 998; Nov. 8, 1984, Pub.L. 98-620,

Title IV, § 402(25)(A), 98 Stat. 3359; June 16, 1992, Pub.L. 102-300, § 6(b)(1), 106 Stat. 240; Oct. 29, 1992,

Pub.L. 102-571, Title I, § 107(7), 106 Stat. 4499; Aug. 13, 1993, Pub.L. 103-80, § 3(k), 107 Stat. 776; Aug. 3,

1996, Pub.L. 104-170, Title IV, § 405, 110 Stat. 1514; Oct. 30, 1998, Pub.L. 105-324, § 2(b), 112 Stat. 3036;

Oct. 9, 2007, Pub.L. 110-94, § 4(d)(2), 121 Stat. 1002.)

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[FN1] So in original. Probably should be “subsection”.

HISTORICAL AND STATUTORY NOTES

Revision Notes and Legislative Reports

1954 Acts. Senate Report No. 1635, see 1954 U.S. Code Cong. and Adm. News, p. 2626.

1958 Acts. Senate Report No. 2129, see 1958 U.S. Code Cong. and Adm. News, p. 3996.

1970 Acts. House Report No. 91-1444 and Conference Report No. 91-1603, see 1970 U.S. Code Cong. and

Adm. News, p. 4566.

1971 Acts. House Report No. 92-258 andHouse Conference Report No. 92-578, see 1971 U.S. Code Cong. and

Adm. News, p. 1610.

1972 Acts. Senate Report Nos. 92-838 and 92-970 and Conference Report No. 92-1540, see 1972 U.S. Code

Cong. and Adm. News, p. 3993.

1984 Acts. House Report No. 98-1062, see 1984 U.S. Code Cong. and Adm. News, p. 5708.

1996 Acts. House Report No. 104-669(Parts I and II), see 1996 U.S. Code Cong. and Adm. News, p. 1208.

References in Text

The Toxic Substances Control Act, referred to in text, is Pub.L. 94-469, Oct. 11, 1976, 90 Stat. 2003, as

amended, which is classified generally to chapter 53 (section 2601 et seq.) of Title 15, Commerce and Trade.

For complete classification of this Act to the Code, see Short Title note set out under section 2601 of Title 15

and Tables.

The Federal Insecticide, Fungicide, and Rodenticide Act, referred to in text, is Act June 25, 1947, c. 125, as

amended generally by Pub.L. 92-516, Oct. 21, 1972, 86 Stat. 973, which is classified generally to subchapter II

(section 136 et seq.) of chapter 6 of Title 7, Agriculture. For complete classification of this Act to the Code, see

Short Title note set out under section 136 of Title 7 and Tables.

Section 346 of this title, referred to in subsec. (j)(1), originally consisted of subsecs. (a) and (b). Subsec. (a) was

redesignated as the entire section 21 U.S.C.A. § 346 and subsec. (b) was repealed by Pub.L. 86-618, Title I, §

103(a)(1), 74 Stat. 398.

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Effective: July 24, 2006

Code of Federal Regulations Currentness

Title 40. Protection of Environment

Chapter I. Environmental Protection Agency

(Refs & Annos)

Subchapter A. General

Part 26. Protection of Human Subjects

(Refs & Annos)

Subpart Q. Ethical Standards for Assessing Whether to Rely on the Results

of Human Research in EPA Actions

(Refs & Annos)

§ 26.1704 Prohibition of reliance

on unethical human research with

non-pregnant, non-nursing adults

conducted before April 7, 2006.

Except as provided in § 26.1706, in actions within

the scope of § 26.1701, EPA shall not rely on data

from any research initiated before April 7, 2006, if

there is clear and convincing evidence that the conduct of the research was fundamentally unethical

(e.g., the research was intended to seriously harm

participants or failed to obtain informed consent),

or was significantly deficient relative to the ethical

standards prevailing at the time the research was

conducted. This prohibition is in addition to the

prohibition in § 26.1703.

[71 FR 36175, June 23, 2006]

SOURCE: 56 FR 28012, 28022, June 18, 1991; 71

FR 6168, 6176, Feb. 6, 2006; 71 FR 6168, Feb. 6,

2006, unless otherwise noted.

AUTHORITY: 5 U.S.C. 301; 7 U.S.C. 136w(a)(1);

21 U.S.C. 346a(e)(1)(C); section 201 of Public Law

No. 109-54; and 42 U.S.C. 300v-1(b).

40 C. F. R. § 26.1704, 40 CFR § 26.1704

Current through July 22, 2010; 75 FR 42610

© 2010 Thomson Reuters

END OF DOCUMENT

40 C.F.R. § 26.1704 Page 1

© 2010 Thomson Reuters. No Claim to Orig. US Gov. Works.

SPA 30
Effective:[See Text Amendments]

Code of Federal Regulations Currentness

Title 40. Protection of Environment

Chapter I. Environmental Protection Agency

(Refs & Annos)

Subchapter E. Pesticide Programs

Part 178. Objections and Requests for

Hearings (Refs & Annos)

Subpart B. Procedures for Filing Objections and Requests for Hearing

§ 178.27 Form and manner of

submission of request for evidentiary hearing.

To be considered by the Administrator, a request

for an evidentiary hearing must meet the criteria in

§ 178.32, and must:

(a) Be submitted as a part of, and specifically request an evidentiary hearing on an objection that

complies with the requirements of § 178.25.

(b) Include a statement of the factual issue(s) on

which a hearing is requested and the requestor's

contentions on each such issue.

(c) Include a copy of any report, article, survey, or

other written document (or the pertinent pages

thereof) upon which the objector relies to justify an

evidentiary hearing, unless the document is an EPA

document that is routinely available to any member

of the public.

(d) Include a summary of any evidence not described in paragraph (a)(3) of this section upon

which the objector relies to justify an evidentiary

hearing.

(e) Include a discussion of the relationship between

the factual issues and the relief requested by the objection.

SOURCE: 55 FR 50291, Dec. 5, 1990; 70 FR

33359, June 8, 2005, unless otherwise noted.

AUTHORITY: 21 U.S.C. 346a, 371(a); Reorg. Plan

No. 3 of 1970.

40 C. F. R. § 178.27, 40 CFR § 178.27

Current through July 22, 2010; 75 FR 42610

© 2010 Thomson Reuters

END OF DOCUMENT

40 C.F.R. § 178.27 Page 1

© 2010 Thomson Reuters. No Claim to Orig. US Gov. Works.

SPA 31
Effective:[See Text Amendments]

Code of Federal Regulations Currentness

Title 40. Protection of Environment

Chapter I. Environmental Protection Agency

(Refs & Annos)

Subchapter E. Pesticide Programs

Part 178. Objections and Requests for

Hearings (Refs & Annos)

Subpart B. Procedures for Filing Objections and Requests for Hearing

§ 178.32 Rulings on requests for

hearing.

(a) In the case of each request for an evidentiary

hearing that was not denied under § 178.30(a) or

(b), the Administrator will determine whether such

a hearing on one or more of the objections is justified, and will publish in the Federal Register the determination in an order issued under § 178.37 or a

Notice of Hearing issued under § 179.20 of this

chapter. If some requests for a hearing are denied

and others pertaining to the same order or regulation are granted, the denial order and the hearing

notice may be combined into a single document and

shall be issued at the same time unless the Administrator for good cause determines otherwise.

(b) A request for an evidentiary hearing will be

granted if the Administrator determines that the material submitted shows the following:

(1) There is a genuine and substantial issue of

fact for resolution at a hearing. An evidentiary

hearing will not be granted on issues of policy

or law.

(2) There is a reasonable possibility that available evidence identified by the requestor

would, if established, resolve one or more of

such issues in favor of the requestor, taking into account uncontested claims or facts to the

contrary. An evidentiary hearing will not be

granted on the basis of mere allegations, denials, or general descriptions of positions and

contentions, nor if the Administrator concludes

that the data and information submitted, even if

accurate, would be insufficient to justify the

factual determination urged.

(3) Resolution of the factual issue(s) in the

manner sought by the person requesting the

hearing would be adequate to justify the action

requested. An evidentiary hearing will not be

granted on factual issues that are not determinative with respect to the action requested. For

example, a hearing will not be granted if the

Administrator concludes that the action would

be the same even if the factual issue were resolved in the manner sought.

(c) Where appropriate, the Administrator will make

rulings on any issues raised by an objection which

are necessary for resolution prior to determining

whether a request for an evidentiary hearing should

be granted.

SOURCE: 55 FR 50291, Dec. 5, 1990; 70 FR

33359, June 8, 2005, unless otherwise noted.

AUTHORITY: 21 U.S.C. 346a, 371(a); Reorg. Plan

No. 3 of 1970.

40 C. F. R. § 178.32, 40 CFR § 178.32

Current through July 22, 2010; 75 FR 42610

© 2010 Thomson Reuters

END OF DOCUMENT

40 C.F.R. § 178.32 Page 1

© 2010 Thomson Reuters. No Claim to Orig. US Gov. Works.

SPA 32
26–049

104TH CONGRESS REPT. 104–669 " ! HOUSE OF REPRESENTATIVES 2d Session Part 2

FOOD QUALITY PROTECTION ACT OF 1996

JULY 23, 1996.—Committed to the Committee of the Whole House on the State of

the Union and ordered to be printed

Mr. BLILEY, from the Committee on Commerce,

submitted the following

R E P O R T

[To accompany H.R. 1627]

[Including cost estimate of the Congressional Budget Office]

The Committee on Commerce, to whom was referred the bill

(H.R. 1627) to amend the Federal Insecticide, Fungicide, and

Rodenticide Act and the Federal Food, Drug, and Cosmetic Act, and

for other purposes, having considered the same, report favorably

thereon with an amendment and recommend that the bill as

amended do pass.

CONTENTS

Page

The Amendment ...................................................................................................... 1

Purpose and Summary ............................................................................................ 29

Background and Need for Legislation .................................................................... 29

Hearings ................................................................................................................... 32

Committee Consideration ........................................................................................ 33

Rollcall Votes ............................................................................................................ 33

Committee Oversight Findings ............................................................................... 34

Committee on Government Reform and Oversight ............................................... 34

New Budget Authority and Tax Expenditures ...................................................... 34

Committee Cost Estimate ....................................................................................... 34

Congressional Budget Office Estimate ................................................................... 35

Inflationary Impact Statement ............................................................................... 37

Advisory Committee Statement .............................................................................. 37

Section-by-Section Analysis of the Legislation ...................................................... 37

Changes in Existing Law Made by the Bill, as Reported ..................................... 56

AMENDMENT

The amendment is as follows:

Page 50, strike line 5 and all that follows through page 91, line

16, and insert the following:

SPA 33
43

sions of this Act, the potential significant disruption that triggered

the action is of the type the Committee envisions as representative.

New Section 408(b)(2)(C)—Exposure to Infants and Children

mandates criteria relating to safety of infants and children to be

considered when establishing, modifying, leaving in effect, or revoking tolerances or exemptions for pesticide residues. In making such

decisions, the Administrator shall (i) assess the risk of the pesticide

residue based on: (I) data on consumption patterns among infants

and children, if these patterns are likely to result in a disproportionately high consumption of foods bearing the residue as compared with the consumption by the general population; (II) data on

the special susceptibility of infants and children to pesticide residues, including data on the neurological differences between infants, children, and adults and effects of in-utero exposure to

chemicals; and (III) data on the cumulative effects on infants and

children of such residues that have common mechanisms of toxicity. In the decision, the Administrator shall also (ii): (I) ensure

that there is a reasonable certainty of no harm to infants and children from aggregate exposure to the pesticide chemical residue;

and (II) publish a determination regarding the safety of the residue

for infants and children.

When data relating to infants and children are incomplete, and

also to account for potential pre- and post-natal toxicity, the Administrator is to apply, under new Section 408(b)(2)(C), an additional tenfold margin of safety for infants and children. However,

EPA may apply a different margin of safety if reliable data indicate

that it will be safe for infants and children. The Secretary of

Health and Human Services (DHHS) and the Secretary of Agriculture (USDA), in consultation with EPA, will document, through

surveys, dietary exposure to pesticides among infants and children.

It is the intention of the Committee that EPA interpret the language of this section in furtherance of the following recommendation of the National Research Council’s Study, ‘‘Pesticides in the

Diets of Infants and Children’’:

At present, to provide added protection during early development, a third uncertainty factor of 10 is applied to

the NOEL, to develop the RfD. This third 10-fold factor

has been applied by the EPA and FDA whenever toxicity

studies and metabolic/disposition studies have shown fetal

developmental effects.

Because there exist specific periods of vulnerability during postnatal development, the committee recommends

that an uncertainty factor up to the 10-fold factor traditionally used by EPA and FDA for fetal developmental toxicity should also be considered when there is evidence of

postnatal developmental toxicity and when data from toxicity testing relative to children are incomplete. The committee wishes to emphasize that this is not a new, additional uncertainty factor but, rather, an extended application of a uncertainty factor now routinely used by the

agencies for a narrower purpose. (page 9)

New Section 408(b)(2)(D)—Factors lists nine factors that EPA

should consider in establishing, modifying, leaving in effect, or reSPA 34
54

all Federal and State laws. An exception is allowed if the State can

demonstrate that the residue level will pose an unreasonable dietary risk to the health of persons within that State due to consumption of that food during the period in which it is likely to be

available.

New subsection (n)(8)—Savings excludes from the preemption

provisions of subsection (n) ‘‘warning requirements’’ and other

statements relating to the presence of such residues in food.

Sec. 408(o). Consumer right to know

This section requires EPA within 2 years of enactment and annually thereafter, in consultation with USDA and DHHS, to publish

and distribute to large retail grocers for public display (in a manner determined by each grocer) certain information relevant to pesticide residues. The information, which must be conveyed in a format understandable to a lay person, includes: (1) a discussion of

the risks and benefits of pesticide chemical residues in or on food;

(2) a list of actions taken under subsection (b)(2)(B) relating to eligible pesticide residues that may result in risks greater than allowed for under subparagraph (A), and of the food on which the

pesticides producing such residues are used; and (3) recommendations on how consumers might reduce dietary exposures to pesticide residues while maintaining a healthy diet. The Committee

expects the EPA recommendations to be consistent with established nutritional guidelines. Retail grocers may provide additional

information.

Sec. 408(p). Estrogenic substances screening program

New Section 408(p)(1) directs EPA, in consultation with DHHS,

to develop a screening program within 2 years to gather information scientifically to evaluate whether certain substances may have

effects in humans that are similar to effects produced by naturally

occurring estrogen or other endocrine effects. Paragraph (2) requires EPA to solicit public comments on and review of the screening program by the scientific advisory panel for pesticide policy or

the EPA science advisory board, which evaluates a broader range

of EPA programs. The program must be implemented within 3

years of enactment of H.R. 1627. Paragraph (3) mandates testing

of all pesticide chemicals and authorizes EPA to test any other substance that may have an effect cumulative to that of a pesticide

chemical residue, if a substantial population may be exposed to it.

Paragraph (4) authorizes EPA to issue orders exempting substances from the testing requirements if they are not expected to

produce an estrogenic effect in humans. EPA must issue an order

to conduct testing of covered substances and to submit reports to

pesticide registrants and to persons who manufacture or import

covered substances. The bill requires such orders to establish a reasonable time period for generating the information and reporting to

EPA. EPA implementing regulations and orders should minimize

duplicative testing requirements, provide equitable arrangements

for sharing testing costs, and develop procedures to handle confidential business information. The other substances that may be

tested under this paragraph are intended by the Committee to be

other environmental contaminants. Paragraph (5)(C) requires issuSPA 35
55

ance of a notice of intent to suspend the sale or distribution of a

substance if a registrant fails to comply with a test order. Such

suspension will become final after 30 days unless a hearing is requested or the EPA decides that the registrant has complied fully

with paragraph (5). However, EPA must terminate a suspension if

the registrant has fully complied with paragraph (5). Any hearing

held will be conducted in accordance with section 554 of title 4

U.S.C. (that is, the formal adjudicatory hearing process). The only

matter to be resolved at the hearing is whether the registrant

failed to comply with an EPA order. An EPA decision after the

hearing is a final agency action and thus may be judicially reviewed under the Administrative Procedure Act (5 U.S.C. 701). If

a manufacturer or an importer who is not a registrant fails to comply with a test order, that person is liable for the penalties and

sanctions provided under TSCA Section 16, which may include up

to $25,000 per day in fines and, if the person knowingly or willfully

violates an order, imprisonment for up to one year. A person assessed a fine may request a hearing and, if ordered to pay the fine

after the hearing, may file a petition for judicial review of EPA’s

order. The bill mandates EPA action ‘‘as is necessary to ensure the

protection of public health’’ if the screening program finds a substance to have an endocrine effect on humans. Any action is to be

taken under EPA’s existing statutory authority. EPA must report

to Congress within 4 years on its findings from the screening program and any recommendations for further testing and actions.

Sec. 408(q). Schedule for review

New Section 408(q) directs EPA to review tolerances and exemptions for pesticide residues in effect before enactment of H.R. 1627.

Review should take place as expeditiously as practicable and assure that (A) 33 percent of the tolerances and exemptions are reviewed within 3 years, (B) 66 percent are reviewed within 6 years,

and (C) all tolerances and exemptions are reviewed within 10

years. In reviewing the tolerances and exemptions, EPA is required

to determine whether they meet the requirements of subsections

(b)(2) or (c)(2). Before the deadline for review, the bill directs EPA

to issue regulations under subsection (d)(4) or (e)(1) to modify or revoke tolerances and exemptions that do not meet the requirements

of subsections (b)(2) or (c)(2).

Paragraph (2) orders the Administrator to give priority to the review of tolerances or exemptions that appear to pose the greatest

risk to public health. New paragraph (3) requires that EPA publish

within 12 months a schedule for review of tolerances and exemptions established prior to enactment of H.R. 1627. Priority setting

for the review of tolerances and exemptions under this subsection

is not to be considered a rulemaking and is not subject to judicial

review. However, if EPA fails to take final action pursuant to the

schedule, this failure shall be subject to judicial review.

In establishing an orderly review of existing tolerances and providing EPA with discretion in setting priorities, the Committee intends for the Agency to align such priorities responsibly with other

important business, such as reviewing and responding to petitions.

The Committee does not intend the petition process to be used in

SPA 36
Federal Register / Vol. 73, No. 142 / Wednesday, July 23, 2008 / Rules and Regulations 42683 

[FR Doc. E8–16833 Filed 7–22–08; 8:45 am] 

BILLING CODE 6560–50–P 

ENVIRONMENTAL PROTECTION 

AGENCY 

40 CFR Part 180 

[EPA–HQ–OPP–2002–0302; FRL–8372–5] 

Dichlorvos (DDVP); Order Denying 

NRDC’s Objections and Requests for 

Hearing 

AGENCY: Environmental Protection 

Agency (EPA). 

ACTION: Final Order. 

SUMMARY: In this order, EPA denies 

objections to, and requests for hearing 

on, a prior order denying a petition 

requesting that EPA revoke all pesticide 

tolerances for dichlorvos under section 

408(d) of the Federal Food, Drug, and 

Cosmetic Act. The objections and 

hearing requests were filed on February 

1, 2008, by the Natural Resources 

Defense Council (‘‘NRDC’’). The 

Original petition was also filed by 

NRDC. 

DATES: This order is effective July 23, 

2008. 

ADDRESSES: EPA has established a 

docket for this action under docket 

identification (ID) number EPA–HQ–

OPP–2002–0302. To access the 

electronic docket, go to http:// 

www.regulations.gov, and search for the 

docket number. Follow the instructions 

on the regulations.gov website to view 

the docket index or access available 

documents. All documents in the docket 

are listed in the docket index available 

in regulations.gov. Although listed in 

the index, some information is not 

publicly available, e.g., Confidential 

Business Information (CBI) or other 

information whose disclosure is 

restricted by statute. Certain other 

material, such as copyrighted material, 

is not placed on the Internet and will be 

publicly available only in hard copy 

form. Publicly available docket 

materials are available in the electronic 

docket at http://www.regulations.gov, 

or, if only available in hard copy, at the 

OPP Regulatory Public Docket in Rm. S4400, One Potomac Yard (South Bldg.), 

2777 S. Crystal Dr., Arlington, VA. The 

Docket Facility is open from 8:30 a.m. 

to 4 p.m., Monday through Friday, 

excluding legal holidays. The Docket 

Facility telephone number is (703) 305- 

5805. 

FOR FURTHER INFORMATION CONTACT: 

Susan Bartow, Special Review and 

Reregistration Division (7508P), Office 

of Pesticide Programs, Environmental 

Protection Agency, 1200 Pennsylvania 

Ave., NW., Washington, DC 20460-0001; 

telephone number: 703-603-0065; e-mail 

address: bartow.susan@epa.gov. 

SUPPLEMENTARY INFORMATION: 

I. General Information 

A. Does this Action Apply to Me? 

In this document EPA denies 

objections and hearing requests by the 

Natural Resources Defense Council 

(‘‘NRDC’’) concerning EPA’s denial of 

NRDC’s petition to revoke pesticide 

tolerances. This action may also be of 

interest to agricultural producers, food 

manufacturers, or pesticide 

manufacturers. Potentially affected 

entities may include, but are not limited 

to those engaged in the following 

activities: 

• 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. 

This listing is not intended to be 

exhaustive, but rather to provide a guide 

for readers regarding entities likely to be 

affected by this action. Other types of 

entities not listed in this unit could also 

be affected. The NAICS codes have been 

provided to assist you and others in 

determining whether this action might 

apply to certain entities. If you have any 

questions regarding the applicability of 

this action to a particular entity, consult 

the person listed under FOR FURTHER

INFORMATION CONTACT. 

B. How Can I Access Electronic Copies 

of this Document? 

In addition to accessing an electronic 

copy of this Federal Register document 

through the electronic docket at http:// 

www.regulations.gov, you may access 

this Federal Register document 

electronically through the EPA Internet 

under the ‘‘Federal Register’’ listings at 

http://www.epa.gov/fedrgstr. You may 

also access a frequently updated 

electronic version of EPA’s tolerance 

regulations at 40 CFR part 180 through 

the Government Printing Office’s pilot 

e-CFR site at http://www.gpoaccess.gov/ 

ecfr. 

C. Acronyms 

The following is a list of acronyms 

used in this order: 

CSFII - Continuing Survey of Food Intakes by 

Individuals 

CNS - Central Nervous System 

DDVP - dichlorvos 

EDSTAC - Endocrine Disruptor Screening 

and Testing Advisory Committee 

EPA - Environmental Protection Agency 

FACA - Federal Advisory Committee Act 

FDA - Food and Drug Administration 

FIFRA - Federal Insecticide, Fungicide, and 

Rodenticide Act 

FFDCA - Federal Food, Drug, and Cosmetic 

Act 

FQPA - Food Quality Protection Act of 1996 

HSRB - Human Studies Review Board 

IRED - Interim Reregistration Eligibility 

Decision 

LOAEL - Lowest Observed Adverse Effect 

Level 

MOE - Margin of Exposure 

MRID - Master Record Identification 

NOAEL - No Observed Adverse Effect Level 

NRDC - Natural Resources Defense Council 

OECD - Organisation for Economic Cooperation and Development 

PAD - Population Adjusted Dose 

ppm - parts per million 

RBC - red blood cell 

RED - Reregistration Eligibility Decision 

RfD - Reference Dose 

SDWA - Safe Drinking Water Act 

SOP - Standard Operating Procedure 

USDA - United Stated Department of 

Agriculture 

II. Introduction 

A. What Action Is the Agency Taking? 

In this order, EPA denies objections, 

and requests for a hearing on those 

objections, 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. (Refs. 1 and 2). Both the objections 

and hearing requests, as well as the 

petition, were filed with EPA by NRDC. 

NRDC’s petition, filed on June 2, 

2006, pursuant to FFDCA section 

408(d)(1), asserted numerous grounds as 

to why the DDVP 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 DDVP tolerances pursuant 

to FFDCA section 408(q). (Ref. 3). In 

response to the petition, EPA undertook 

an extensive review of its DDVP safety 

evaluation in the tolerance reassessment 

decision. Based on certain concerns 

raised by NRDC, EPA determined it was 

necessary to incorporate updated data 

on numerous points and to adopt 

revised and more conservative 

assumptions, in its DDVP risk 

assessments. This led to complete 

revisions of both EPA’s assessments of 


sroberts on PROD1PC70 with RULES

SPA 37
42684 Federal Register / Vol. 73, No. 142 / Wednesday, July 23, 2008 / Rules and Regulations 

dietary and residential risks from 

exposure to DDVP. (72 FR at 68678, 

68687-68691). Nonetheless, EPA 

concluded that its revised risk 

assessments demonstrated that DDVP 

met the FFDCA safety standard and, 

therefore, denied the petition. (Id. at 

68695). EPA’s denial was issued in the 

form of an order under FFDCA section 

408(d)(4)(iii). (21 U.S.C. 346a(d)(4)(iii)). 

NRDC then filed objections with EPA 

to the petition denial order and 

requested a hearing on its objections. 

These objections and hearing requests 

were filed pursuant to the procedures in 

the FFDCA section 408(g)(2). (21 U.S.C. 

346a(g)(2)). The objections narrowed 

NRDC’s claims to two main topics - that, 

in assessing the risk to DDVP, EPA 

unlawfully reduced the statutory safety 

factor for the protection of infants and 

children and EPA unlawfully relied on 

a human toxicity study. As to these 

claims, NRDC largely repeats the 

arguments as presented in its petition 

without addressing EPA’s substantial 

revisions to the DDVP risk assessment 

and proffers little to no evidence in 

support of its requests for a hearing. 

After carefully reviewing the objections 

and hearing requests, EPA has 

determined that NRDC’s hearing 

requests do not satisfy the regulatory 

requirements for such requests and that 

its substantive objections are without 

merit. Therefore, EPA, in this final 

order, denies NRDC’s objections and its 

requests for a hearing on those 

objections. 

B. What Is the Agency’s Authority for 

Taking This Action? 

NRDC petitioned to revoke the DDVP 

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 statutorilycreated 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)). 

III. Statutory and Regulatory 

Background 

In this Unit, EPA provides 

background on the relevant statutes and 

regulations governing NRDC’s 

objections and requests for hearing as 

well as on pertinent Agency policies 

and practices. As noted, NRDC’s 

objections and requests for hearing raise 

two main claims: (1) that EPA has 

unlawfully failed to retain the full 

tenfold safety factor for the protection of 

infants and children; and (2) that it was 

unlawful for EPA to rely on a toxicity 

study for DDVP that was conducted 

with humans. The children’s safety 

factor claim is based on assertions 

regarding DDVP’s potential endocrine 

effects and the adequacy of EPA’s data 

and risk assessments pertaining to 

exposure to DDVP in food as a result of 

the use of DDVP (and similar pesticides) 

in agriculture or food storage and 

through use of DDVP in residential 

settings. The human studies claim 

involves a challenge to the EPA 

regulation governing reliance on human 

studies as well as to EPA’s application 

of that rule to a particular human study. 

The human study in question measured 

cholinesterase inhibition in humans 

resulting from administration of DDVP. 

Background information on each of 

these topics is included in this Unit. 

Unit III.A. summarizes the 

requirements and procedures in section 

408 of the FFDCA and applicable 

regulations pertaining to pesticide 

tolerances, including the procedures for 

petitioning for revocation of tolerances 

and challenging the denial of such 

petitions and the substantive standards 

for evaluating the safety of pesticide 

tolerances. This unit also discusses the 

closely-related statute under which EPA 

regulates the sale, distribution, and use 

of pesticides, the Federal Insecticide, 

Fungicide, and Rodenticide Act 

(‘‘FIFRA’’), (7 U.S.C. 136 et seq.). 

Unit III.B. provides an overview of 

EPA’s risk assessment process. It 

contains an explanation of how EPA 

identifies the hazards posed by 

pesticides, how EPA determines the 

level of exposure to pesticides that pose 

a concern (‘‘level of concern’’), how EPA 

measures human exposure to pesticides, 

and how hazard, level of concern 

conclusions, and human exposure 

estimates are combined to evaluate risk. 

Further, this unit presents background 

information on two Agency policies 

with particular relevance to this action, 

EPA’s policy with regard to the statutory 

safety factor for the protection of infants 

and children and its policy with regard 

to cholinesterase inhibition. 

Unit III.C. summarizes EPA’s program 

for implementing the statutory 

requirement to screen pesticides for 

potential endocrine effects. Unit III.D. 

describes the EPA regulation on use of 

human studies. 

A. FFDCA/FIFRA and Applicable 

Regulations 

1. In general. EPA establishes 

maximum residue limits, or 

‘‘tolerances,’’ for pesticide residues in 

food under section 408 of the FFDCA. 

(21 U.S.C. 346a). Without such a 

tolerance or an exemption from the 

requirement of a tolerance, a food 

containing a pesticide residue is 

‘‘adulterated’’ under section 402 of the 

FFDCA and may not be legally moved 

in interstate commerce. (21 U.S.C. 331, 

342). Monitoring and enforcement of 

pesticide tolerances are carried out by 

the U.S. Food and Drug Administration 

(‘‘FDA’’) and the U.S. Department of 

Agriculture (‘‘USDA’’). Section 408 was 

substantially rewritten by the Food 

Quality Protection Act of 1996 

(‘‘FQPA’’), which added the provisions 

discussed below establishing a detailed 

safety standard for pesticides, additional 

protections for infants and children, and 

the estrogenic substances screening 

program. (Public Law 104-170, 110 Stat. 

1489 (1996)). 

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)). 

In the FQPA, Congress integrated action 

under the two statutes by requiring that 

the safety standard under the FFDCA be 

used as a criterion in FIFRA registration 

actions as to pesticide uses which result 

in dietary risk from residues in or on 

food, (7 U.S.C. 136(bb)), and directing 

that EPA coordinate, to the extent 

practicable, revocations of tolerances 

with pesticide cancellations under 

FIFRA. (21 U.S.C. 346a(l)(1)). 

2. Safety standard for pesticide 

tolerances. A pesticide tolerance may 

only be promulgated by EPA if the 

tolerance is ‘‘safe.’’ (21 U.S.C. 

346a(b)(2)(A)(i)). ‘‘Safe’’ is defined by 

the statute to mean that ‘‘there is a 

reasonable certainty that no harm will 


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result from aggregate exposure to the 

pesticide chemical residue, including 

all anticipated dietary exposures and all 

other exposures for which there is 

reliable information.’’ (21 U.S.C. 

346a(b)(2)(A)(ii)). Section 408(b)(2)(D) 

directs EPA, in making a safety 

determination, to: 

consider, among other relevant 

factors- ... 

(v) available information concerning the 

cumulative effects of such residues and other 

substances that have a common mechanism 

of toxicity; 

(vi) available information concerning the 

aggregate exposure levels of consumers (and 

major identifiable subgroups of consumers) 

to the pesticide chemical residue and to other 

related substances, including dietary 

exposure under the tolerance and all other 

tolerances in effect for the pesticide chemical 

residue, and exposure from other nonoccupational sources; 

(viii) such information as the 

Administrator may require on whether the 

pesticide chemical may have an effect in 

humans that is similar to an effect produced 

by a naturally occurring estrogen or other 

endocrine effects. ... 

(21 U.S.C. 346a(b)(2)(D)(v), (vi) and 

(viii)). 

EPA must also consider, in evaluating 

the safety of tolerances, ‘‘safety factors 

which . . . are generally recognized as 

appropriate for the use of animal 

experimentation data.’’ (21 U.S.C. 

346a(b)(2)(D)(ix). 

Risks to infants and children are given 

special consideration. Specifically, 

section 408(b)(2)(C) states that EPA: 

shall assess the risk of the pesticide 

chemical based on— ... 

(II) available information concerning the 

special susceptibility of infants and children 

to the pesticide chemical residues, including 

neurological differences between infants and 

children and adults, and effects of in utero 

exposure to pesticide chemicals; and 

(III) available information concerning the 

cumulative effects on infants and children of 

such residues and other substances that have 

a common mechanism of toxicity. ... 

(21 U.S.C. 346a(b)(2)(C)(i)(II) and (III)). 

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.). The additional safety margin for 

infants and children is referred to 

throughout this order as the ‘‘children’s 

safety factor.’’

3. Procedures for establishing, 

amending, or revoking tolerances. 

Tolerances are established, amended, or 

revoked by rulemaking under the 

unique procedural framework set forth 

in the FFDCA. Generally, a tolerance 

rulemaking is initiated by the party 

seeking to establish, amend, or revoke a 

tolerance by means of filing a petition 

with EPA. (See 21 U.S.C. 346a(d)(1)). 

EPA publishes in the Federal Register a 

notice of the petition filing and requests 

public comment. (21 U.S.C. 346a(d)(3)). 

After reviewing the petition, and any 

comments received on it, EPA may issue 

a final rule establishing, amending, or 

revoking the tolerance, issue a proposed 

rule to do the same, or deny the 

petition. (21 U.S.C. 346a(d)(4)). 

Once EPA takes final action on the 

petition by either establishing, 

amending, or revoking the tolerance or 

denying the petition, any person may 

file objections with EPA 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 ‘‘which, 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)). EPA’s 

final order on the objections is subject 

to judicial review. (21 U.S.C. 

346a(h)(1)). 

4. Tolerance reassessment and FIFRA 

reregistration. The FQPA required that 

EPA reassess the safety of all pesticide 

tolerances existing at the time of its 

enactment. (21 U.S.C. 346a(q)). EPA was 

given 10 years to reassess the 

approximately 10,000 tolerances in 

existence in 1996. In this reassessment, 

EPA was required to review existing 

pesticide tolerances under the new 

‘‘reasonable certainty that no harm will 

result’’ standard set forth in section 

408(b)(2)(A)(i). (21 U.S.C. 

346a(b)(2)(A)(i)). This reassessment was 

substantially completed by the August 

3, 2006 deadline. Tolerance 

reassessment was generally handled in 

conjunction with a similar program 

involving reregistration of pesticides 

under FIFRA. (7 U.S.C. 136a-1). 

Reassessment and reregistration 

decisions were generally combined in a 

document labeled a Reregistration 

Eligibility Decision (‘‘RED’’). 

5. Estrogenic substances screening 

program. The FQPA also imposed 

requirements regarding creation of an 

estrogenic substances screening 

program. Section 408(p) gives EPA 2 

years from enactment of the FQPA to 

‘‘develop a screening program ... to 

determine whether [pesticide chemicals 

and certain other substances] may have 

an effect in humans that is similar to an 

effect produced by a naturally occurring 

estrogen, or such other endocrine effect 

as the Administrator may designate.’’

(21 U.S.C. 346a(p)(1)). This screening 

program must use ‘‘appropriate 

validated test systems and scientifically 

relevant information.’’ (Id.). Once the 

program is developed, EPA is required 

to take public comment and seek 

independent scientific review of it. 

Following the period for public 

comment and scientific review, and not 

later than 3 years following enactment 

of the FQPA, EPA is directed to 

‘‘implement the program.’’ (21 U.S.C. 

346a(p)(2)). 

The scope of the estrogenic screening 

program was expanded by an 

amendment to the Safe Drinking Water 

Act (‘‘SDWA’’) passed 

contemporaneously with the FQPA. 

That amendment gave EPA the authority 

to provide for the testing, under the 

FQPA estrogenic screening program, ‘‘of 

any other substance that may be found 

in sources of drinking water if the 

Administrator determines that a 

substantial population may be exposed 

to such substance.’’ (42 U.S.C. 300j-17). 

B. EPA Risk Assessment for 

Tolerances—Policy and Practice 

1. The safety determination - risk 

assessment. To assess risk of a pesticide 

tolerance, EPA combines information on 

pesticide toxicity with information 

regarding the route, magnitude, and 

duration of exposure to the pesticide. 

The risk assessment process involves 

four distinct steps: (1) Identification of 

the toxicological hazards posed by a 

pesticide; (2) determination of the ‘‘level 

of concern’’ with respect to human 

exposure to the pesticide; (3) estimation 

of human exposure to the pesticide; and 

(4) characterization of risk posed to 

humans by the pesticide based on 

comparison of human exposure to the 

level of concern. 

a. Hazard identification. In evaluating 

toxicity or hazard, EPA reviews toxicity 

studies, primarily in laboratory animals, 


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to identify any adverse effects on the 

test subjects. Animal studies typically 

involve investigating a broad range of 

endpoints including gross and 

microscopic effects on organs and 

tissues, functional effects on bodily 

organs and systems, effects on blood 

parameters (such as red blood cell 

count, hemoglobin concentration, 

hematocrit, and a measure of clotting 

potential), effects on the concentrations 

of normal blood chemicals (including 

glucose, total cholesterol, urea nitrogen, 

creatinine, total protein, total bilirubin, 

albumin, hormones, and enzymes such 

as alkaline phosphatase, alanine 

aminotransfersase and cholinesterases), 

and behavioral or other gross effects 

identified through clinical observation 

and measurement. EPA examines 

whether adverse effects are caused by 

either short-term (e.g., ‘‘acute’’) or 

longer-term (e.g., ‘‘chronic’’) pesticide 

exposure and the effects of pre-natal and 

post-natal exposure in animals. 

EPA also considers whether the 

adverse effect has a threshold - a level 

below which exposure has no 

appreciable chance of causing the 

adverse effect. For non-threshold effects, 

EPA assumes that any exposure to the 

substance increases the risk that the 

adverse effect may occur. At present, 

EPA only considers one adverse effect, 

the chronic effect of cancer, to 

potentially be a non-threshold effect. 

(Ref. 4 at 8-9). Not all carcinogens, 

however, pose a risk at any exposure 

level (i.e., ‘‘a non-threshold effect or 

risk’’). Advances in the understanding 

of the mode of action of carcinogenesis 

have increasingly led EPA to conclude 

that some pesticides that cause 

carcinogenic effects in animal studies 

only cause such effects above a certain 

threshold of exposure. EPA has 

traditionally considered non-cancer 

adverse effects on the endocrine system 

to be threshold effects; that 

determination is being reexamined in 

conjunction with the endocrine 

disruptor screening program. 

b. Level of concern/dose-response 

analysis. Once a pesticide’s potential 

hazards are identified, EPA determines 

a toxicological level of concern for 

evaluating the risk posed by human 

exposure to the pesticide. In this step of 

the risk assessment process, EPA 

essentially evaluates the levels of 

exposure to the pesticide at which 

effects might occur. An important aspect 

of this determination is assessing the 

relationship between exposure (dose) 

and response (often referred to as the 

dose-response analysis). EPA follows 

differing approaches to identifying a 

level of concern for threshold and nonthreshold hazards. 

i. Threshold effects. In examining the 

dose-response relationship for a 

pesticide’s threshold effects, EPA 

evaluates an array of toxicity studies on 

the pesticide. In each of these studies, 

EPA attempts to identify the lowest 

observed adverse effect level (‘‘LOAEL’’) 

and the next lower dose at which there 

are no observed adverse affect levels 

(‘‘NOAEL’’). Generally, EPA will use the 

lowest NOAEL from the available 

studies as a starting point (called ‘‘the 

Point of Departure’’) in estimating the 

level of concern for humans. (Ref. 4 at 

9 (The Point of Departure ‘‘is simply the 

toxic dose that serves as the ‘starting 

point’ in extrapolating a risk to the 

human population.’’)). At times, 

however, EPA will use a LOAEL from a 

study as the Point of Departure when no 

NOAEL is identified in that study and 

the LOAEL is close to, or lower than, 

other relevant NOAELs. The Point of 

Departure is in turn used in choosing a 

level of concern. EPA will make 

separate determinations as to the Points 

of Departure, and correspondingly 

levels of concern, for both short and 

long exposure periods as well as for the 

different routes of exposure (oral, 

dermal, and inhalation). 

In estimating and describing the level 

of concern, the Point of Departure is at 

times used differently depending on 

whether the risk assessment addresses 

dietary or non-dietary exposures. For 

dietary risks, EPA uses the Point of 

Departure to calculate an acceptable 

level of exposure or reference dose 

(‘‘RfD’’). The RfD is calculated by 

dividing the Point of Departure by all 

applicable safety or uncertainty factors. 

Typically, EPA uses a baseline safety/ 

uncertainty factor equal to 100. That 

value includes a factor of ten (‘‘10X’’) 

where EPA is using data from laboratory 

animals to reflect potentially greater 

sensitivity in humans than animals and 

a factor of 10X to account for potential 

variations in sensitivity among members 

of the human population as well as 

other unknowns. Additional safety 

factors may be added to address data 

deficiencies or concerns raised by the 

existing data. Under the FQPA, an 

additional safety factor of 10X is 

presumptively applied to protect infants 

and children, unless reliable data 

support selection of a different factor. 

This FQPA additional safety factor 

largely replaces pre-FQPA EPA practice 

regarding additional safety factors. (Ref. 

5 at 4-11). 

In implementing FFDCA section 408, 

EPA’s Office of Pesticide Programs, also 

calculates a variant of the RfD referred 

to as a Population Adjusted Dose 

(‘‘PAD’’). A PAD is the RfD divided by 

any portion of the FQPA safety factor 

that does not correspond to one of the 

traditional additional safety factors used 

in general Agency risk assessments. 

(Ref. 5 at 13-16). The reason for 

calculating PADs is so that other parts 

of the Agency, which are not governed 

by FFDCA section 408, can, when 

evaluating the same or similar 

substances, easily identify which 

aspects of a pesticide risk assessment 

are a function of the particular statutory 

commands in FFDCA section 408. 

Today, RfDs and PADs are generally 

calculated for both acute and chronic 

dietary risks although traditionally a 

RfD or PAD was only calculated for 

chronic dietary risks. Throughout this 

document general references to EPA’s 

calculated safe dose are denoted as a 

RfD/PAD. 

For non-dietary, and combined 

dietary and non-dietary, risk 

assessments of threshold effects, the 

toxicological level of concern is not 

expressed as a RfD/PAD but rather in 

terms of an acceptable (or ‘‘target’’) 

margin of exposure (‘‘MOE’’) between 

human exposure and the Point of 

Departure. The ‘‘margin’’ of interest is 

the ratio between human exposure and 

the Point of Departure which is 

calculated by dividing human exposure 

into the Point of Departure. An 

acceptable MOE is generally considered 

to be a margin at least as high as the 

product of all applicable safety factors 

for a pesticide. For example, if a 

pesticide needs a 10X factor to account 

for inter-species differences, 10X factor 

for intra-species differences, and 10X 

factor for the FQPA children’s safety 

provision, the safe or target MOE would 

be a MOE of at least 1,000. What that 

means is that for the pesticide to meet 

the safety standard, human exposure to 

the pesticide would have to be at least 

1,000 times smaller than the Point of 

Departure. Like RfD/PADs, specific 

target MOEs are selected for exposures 

of different durations. For non-dietary 

exposures, EPA typically examines 

short-term, intermediate-term, and longterm exposures. Additionally, target 

MOEs may be selected based on both 

the duration of exposure and the various 

routes of non-dietary exposure - dermal, 

inhalation, and oral. 

ii. Non-threshold effects. For risk 

assessments for non-threshold effects, 

EPA does not use the RfD/PAD or MOE 

approach to choose a level of concern if 

quantification of the risk is deemed 

appropriate. Rather, EPA calculates the 

slope of the dose-response curve for the 

non-threshold effects from relevant 

studies using a linear, low-dose 

extrapolation model that assumes that 

any amount of exposure will lead to 

some degree of risk. This dose-response 


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analysis will be used in the risk 

characterization stage to estimate the 

risk to humans of the non-threshold 

effect. Linear, low-dose extrapolation is 

typically used as the default approach 

for estimating the risk to carcinogens, 

unless there are mode of action data 

indicating a threshold response (or 

nonlinearity). 

c. Estimating human exposure. Risk is 

a function of both hazard and exposure. 

Thus, equally important to the risk 

assessment process as determining the 

hazards posed by a pesticide and the 

toxicological level of concern for those 

hazards is estimating human exposure. 

Under FFDCA section 408, EPA is 

concerned not only with exposure to 

pesticide residues in food but also 

exposure resulting from pesticide 

contamination of drinking water 

supplies and from use of pesticides in 

the home or other non-occupational 

settings. (See 21 U.S.C. 

346a(b)(2)(D)(vi)). 

i. Exposure from food. There are two 

critical variables in estimating exposure 

in food: (1) The types and amount of 

food that is consumed; and (2) the 

residue level in that food. Consumption 

is estimated by EPA based on scientific 

surveys of individuals’ food 

consumption in the United States 

conducted by the USDA. (Ref. 4 at 12). 

Information on residue values comes 

from a range of sources including crop 

field trials, data on pesticide reduction 

(or concentration) due to processing, 

cooking, and other practices, 

information on the extent of usage of the 

pesticide, and monitoring of the food 

supply. (Id. at 17). 

In assessing exposure from pesticide 

residues in food, EPA, for efficiency’s 

sake, follows a tiered approach in which 

it, in the first instance, assesses 

exposure using the worst case 

assumptions that 100 percent of the 

crop in question is treated with the 

pesticide and 100 percent of the food 

from that crop contains pesticide 

residues at the tolerance level. (Id. at 

11). When such an assessment shows no 

risks of concern, a more complex risk 

assessment is unnecessary. By avoiding 

a more complex risk assessment, EPA’s 

resources are conserved and regulated 

parties are spared the cost of any 

additional studies that may be needed. 

If, however, a first tier assessment 

suggests there could be a risk of 

concern, EPA then attempts to refine its 

exposure assumptions to yield a more 

realistic picture of residue values 

through use of data on the percent of the 

crop actually treated with the pesticide 

and data on the level of residues that 

may be present on the treated crop. 

These latter data are used to estimate 

what has been traditionally referred to 

by EPA as ‘‘anticipated residues.’’

Use of percent crop treated data and 

anticipated residue information is 

appropriate because EPA’s worst-case 

assumptions of 100 percent treatment 

and residues at tolerance value 

significantly overstate residue values. 

There are several reasons this is true. 

First, all growers of a particular crop 

would rarely choose to apply the same 

pesticide to that crop; generally, the 

proportion of the crop treated with a 

particular pesticide is significantly 

below 100 percent. (70 FR 46706, 46731 

(August 10, 2005)). Second, the 

tolerance value represents a high end or 

worst case value. Tolerance values are 

chosen only after EPA has evaluated 

data from experimental crop field trials 

in which the pesticide has been used in 

a manner, consistent with the draft 

FIFRA label, that is likely to produce 

the highest residue in the crop in 

question (e.g., maximum application 

rate, maximum number of applications, 

minimum pre-harvest interval between 

last pesticide application and harvest). 

(Refs. 4 and 6). These crop field trials 

are generally conducted in several fields 

at several geographical locations. (Id. at 

5, 7 and Tables 1 and 5). Several 

samples are then gathered from each 

field and analyzed. (Id. at 53). 

Generally, the results from such field 

trials show that the residue levels for a 

given pesticide use will vary from as 

low as non-detectable to measurable 

values in the parts per million (‘‘ppm’’) 

range with the majority of the values 

falling at the lower part of the range. (70 

FR at 46731). EPA uses a statistical 

procedure to analyze the field trial 

results and identify the upper bound of 

expected residue values. This upper 

bound value is used as the tolerance 

value. (Ref. 7). There may be some 

commodities from a treated crop that 

approach the tolerance value where the 

maximum label rates are followed, but 

most generally fall significantly below 

the tolerance value. If less than the 

maximum legal rate is applied, residues 

will be even lower. Third, residue 

values in the field do not take into 

account the lowering of residue values 

that frequently occurs as a result of 

degradation over time and through food 

processing and cooking. 

EPA uses several techniques to refine 

residue value estimates. (Ref. 4 at 17- 

28). First, where appropriate, EPA will 

take into account all the residue values 

reported in the crop field trials, either 

through use of an average or 

individually. Second, EPA will consider 

data showing what portion of the crop 

is not treated with the pesticide. Third, 

data can be produced showing pesticide 

degradation and decline over time, and 

the effect of commercial and consumer 

food handling and processing practices. 

Finally, EPA can consult monitoring 

data gathered by the FDA, the USDA, or 

pesticide registrants, on pesticide levels 

in food at points in the food distribution 

chain distant from the farm, including 

retail food establishments. 

Another critical component of the 

exposure assessment is how data on 

consumption patterns are combined 

with data on pesticide residue levels in 

food. Traditionally, EPA has calculated 

exposure by simply multiplying average 

consumption by average residue values 

for estimating chronic risks and highend consumption by maximum residue 

values for estimating acute risks. Using 

average residues is a realistic approach 

for chronic risk assessment due to the 

fact that variations in residue levels and 

consumption amounts average out over 

time. Using average values is 

inappropriate for acute risk assessments, 

however, because in assessing acute 

exposure situations it matters how 

much of each treated food a given 

consumer eats and what the residue 

levels are in the particular foods 

consumed. Yet, using maximum residue 

values for acute risk assessment tends to 

greatly overstate exposure because it is 

unlikely that a person would consume 

at a single meal multiple food 

components bearing high-end residues. 

To take into account the variations in 

short-term consumption patterns and 

food residue values for acute risk 

assessments, EPA has more recently 

begun using probabilistic modeling 

techniques for estimating exposure 

when more simplistic models appear to 

show risks of concerns. 

All of these refinements to the 

exposure assessment process, from use 

of food monitoring data through 

probabilistic modeling, can have 

dramatic effects on the level of exposure 

predicted, reducing worst case estimates 

by 1 or 2 orders of magnitude or more. 

(Ref. 8 at 16-17; 70 FR 46706, 46732 

(August 10, 2005). 

ii. Exposure from water. EPA may use 

either or both field monitoring data and 

mathematical water exposure models to 

generate pesticide exposure estimates in 

drinking water. Monitoring and 

modeling are both important tools for 

estimating pesticide concentrations in 

water and can provide different types of 

information. Monitoring data can 

provide estimates of pesticide 

concentrations in water that are 

representative of specific agricultural or 

residential pesticide practices and 

under environmental conditions 

associated with a sampling design. 

Although monitoring data can provide a 


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direct measure of the concentration of a 

pesticide in water, it does not always 

provide a reliable estimate of exposure 

because sampling may not occur in 

areas with the highest pesticide use, 

and/or the sampling may not occur 

when the pesticides are being used. 

In estimating pesticide exposure 

levels in drinking water, EPA most 

frequently uses mathematical water 

exposure models. EPA’s models are 

based on extensive monitoring data and 

detailed information on soil properties, 

crop characteristics, and weather 

patterns. (69 FR 30042, 30058-30065 

(May 26, 2004)). These models calculate 

estimated environmental concentrations 

of pesticides using laboratory data that 

describe how fast the pesticide breaks 

down to other chemicals and how it 

moves in the environment. These 

concentrations can be estimated 

continuously over long periods of time, 

and for places that are of most interest 

for any particular pesticide. Modeling is 

a useful tool for characterizing 

vulnerable sites, and can be used to 

estimate peak concentrations from 

infrequent, large storms. 

iii. Residential exposures. Generally, 

in assessing residential exposure to 

pesticides EPA relies on its Residential 

Standard Operating Procedures 

(‘‘SOPs’’). (Ref. 9). The SOPs establish 

models for estimating application and 

post-application exposures in a 

residential setting where pesticidespecific monitoring data are not 

available. SOPs have been developed for 

many common exposure scenarios 

including pesticide treatment of lawns, 

garden plants, trees, swimming pools, 

pets, and indoor surfaces including 

crack and crevice treatments. The SOPs 

are based on existing monitoring and 

survey data including information on 

activity patterns, particularly for 

children. Where available, EPA relies on 

pesticide-specific data in estimating 

residential exposures. 

d. Risk characterization. The final 

step in the risk assessment is risk 

characterization. In this step, EPA 

combines information from the first 

three steps (hazard identification, level 

of concern/dose-response analysis, and 

human exposure assessment) to 

quantitatively estimate the risks posed 

by a pesticide. Separate 

characterizations of risk are conducted 

for different durations of exposure. 

Additionally, separate and, where 

appropriate, aggregate characterizations 

or risk are conducted for the different 

routes of exposure (dietary and nondietary). 

For threshold risks, EPA estimates 

risk in one of two ways. Where EPA has 

calculated a RfD/PAD, risk is estimated 

by expressing human exposure as a 

percentage of the RfD/PAD. Exposures 

lower than 100 percent of the RfD/PAD 

are generally not of concern. 

Alternatively, EPA may express risk by 

comparing the MOE between estimated 

human exposure and the Point of 

Departure with the acceptable or target 

MOE. As described above, the 

acceptable or target MOE is the product 

of all applicable safety factors. To 

calculate the actual MOE for a pesticide, 

estimated human exposure to the 

pesticide is divided into the Point of 

Departure. In contrast to the RfD/PAD 

approach, the higher the MOE, the safer 

the pesticide. Accordingly, if the target 

MOE for a pesticide is 100, MOEs equal 

to or exceeding 100 would generally not 

be of concern. 

As a conceptual matter, the RfD/PAD 

and MOE approaches are fundamentally 

equivalent. For a given risk and given 

exposure of a pesticide, if exposure to 

a pesticide were found to be acceptable 

under an RfD/PAD analysis it would 

also pass under the MOE approach, and 

vice-versa. However, for any specific 

pesticide, risk assessments for different 

exposure durations or routes may yield 

different results. This is a function not 

of the choice of the RfD/PAD or MOE 

approach but of the fact that the levels 

of concern and the levels of exposure 

may differ depending on the duration 

and route of exposure. 

For non-threshold risks (generally, 

cancer risks), EPA uses the slope of the 

dose-response curve for a pesticide in 

conjunction with an estimation of 

human exposure to that pesticide to 

estimate the probability of occurrence of 

additional adverse effects. For nonthreshold cancer risks, EPA generally 

considers cancer risk to be negligible if 

the probability of increased cancer cases 

falls within the range of 1 in 1 million. 

Risks exceeding values within that 

range would raise a risk concern. 

2. EPA policy on the children’s safety 

factor. As the above brief summary of 

EPA’s risk assessment practice 

indicates, the use of safety factors plays 

a critical role in the process. This is true 

for traditional 10X safety factors to 

account for potential differences 

between animals and humans when 

relying on studies in animals (interspecies safety factor) and potential 

differences among humans (intraspecies safety factor) as well as the 

FQPA’s additional 10X children’s safety 

factor. 

In applying the children’s safety 

factor provision, EPA has interpreted it 

as imposing a presumption in favor of 

applying an additional 10X safety factor. 

(Ref. 5 at 4, 11). Thus, EPA generally 

refers to the additional 10X factor as a 

presumptive or default 10X factor. EPA 

has also made clear, however, that this 

presumption or default in favor of the 

additional 10X is only a presumption. 

The presumption can be overcome if 

reliable data demonstrate that a different 

factor is safe for children. (Id.). In 

determining whether a different factor is 

safe for children, EPA focuses on the 

three factors listed in section 

408(b)(2)(C) - the completeness of the 

toxicity database, the completeness of 

the exposure database, and potential 

pre- and post-natal toxicity. In 

examining these factors, EPA strives to 

make sure that its choice of a safety 

factor, based on a weight-of-theevidence evaluation, does not 

understate the risk to children. (Id. at 

24-25, 35). 

3. EPA policy on cholinesterase 

inhibition as a regulatory endpoint. 

Cholinesterase inhibition is a disruption 

of the normal process in the body by 

which the nervous system chemically 

communicates with muscles and glands. 

Communication between nerve cells 

and a target cell (i.e., another nerve cell, 

a muscle fiber, or a gland) is facilitated 

by the chemical, acetylcholine. When a 

nerve cell is stimulated it releases 

acetylcholine into the synapse (or space) 

between the nerve cell and the target 

cell. The released acetylcholine binds to 

receptors in the target cell, stimulating 

the target cell in turn. As EPA has 

explained, ‘‘the end result of the 

stimulation of cholinergic pathway(s) 

includes, for example, the contraction of 

smooth (e.g., in the gastrointestinal 

tract) or skeletal muscle, changes in 

heart rate or glandular secretion (e.g., 

sweat glands) or communication 

between nerve cells in the brain or in 

the autonomic ganglia of the peripheral 

nervous system.’’ (Ref. 10 at 10). 

Acetylcholinesterase is an enzyme 

that breaks down acetylcholine and 

terminates its stimulating action in the 

synapse between nerve cells and target 

cells. When acetylcholinesterase is 

inhibited, acetylcholine builds up 

prolonging the stimulation of the target 

cell. This excessive stimulation 

potentially results in a broad range of 

adverse effects on many bodily 

functions including muscle cramping or 

paralysis, excessive glandular 

secretions, or effects on learning, 

memory, or other behavioral parameters. 

Depending on the degree of inhibition 

these effects can be serious, even fatal. 

EPA’s cholinesterase inhibition policy 

statement explains EPA’s approach to 

evaluating the risks posed by 

cholinesterase-inhibiting pesticides 

such as DDVP. (Ref. 10). The policy 

focuses on three types of effects 

associated with cholinesteraseVerDate Aug<31>2005 16:31 Jul 22, 2008 Jkt 214001 PO 00000 Frm 00018 Fmt 4700 Sfmt 4700 E:\FR\FM\23JYR1.SGM 23JYR1

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inhibiting pesticides that may be 

assessed in animal and human 

toxicological studies: (1) Physiological 

and behavioral/functional effects; (2) 

cholinesterase inhibition in the central 

and peripheral nervous system; and (3) 

cholinesterase inhibition in red blood 

cells and blood plasma. The policy 

discusses how such data should be 

integrated in deriving an acceptable 

dose (RfD/PAD) for a cholinesteraseinhibiting pesticide. 

Clinical signs or symptoms of 

cholinesterase inhibition in humans, the 

policy concludes, provide the most 

direct evidence of the adverse 

consequences of exposure to 

cholinesterase-inhibiting pesticides. 

Nonetheless, as the policy notes, due to 

strict ethical limitations, studies in 

humans are ‘‘quite limited.’’ (Id. at 19). 

Although animal studies can also 

provide direct evidence of 

cholinesterase inhibition effects, animal 

studies cannot easily measure cognitive 

effects of cholinesterase inhibition such 

as effects on perception, learning, and 

memory. For these reasons, the policy 

recommends that ‘‘functional data 

obtained from human and animal 

studies should not be relied on solely, 

to the exclusion of other kinds of 

pertinent information, when weighing 

the evidence for selection of the critical 

effect(s) that will be used as the basis of 

the RfD or RfC.’’ (Id. at 20). 

After clinical signs or symptoms, 

cholinesterase inhibition in the nervous 

system provides the next most 

important endpoint for evaluating 

cholinesterase-inhibiting pesticides. 

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.’’ (Id. at 25). 

As such, the policy states that it should 

be treated as ‘‘direct evidence of 

potential adverse effects’’ and ‘‘data 

showing this response provide valuable 

information in assessing potential 

hazards posed by anticholinesterase 

pesticides.’’ (Id.). Unfortunately, useful 

data measuring cholinesterase 

inhibition in the central and peripheral 

nervous systems has only been 

relatively rarely captured by standard 

toxicology testing, particularly as to 

peripheral nervous system effects. For 

central nervous system effects, however, 

more recent neurotoxicity studies ‘‘have 

sought to characterize the time course of 

inhibition in ... [the] brain, including 

brain regions, after acute and 90–day 

exposures.’’ (Id. at 27). 

Cholinesterase inhibition in the blood 

is one step further removed from the 

direct harmful consequences of 

cholinesterase-inhibiting pesticides. 

According to the policy, inhibition of 

blood cholinesterases ‘‘is not an adverse 

effect, but may indicate a potential for 

adverse effects on the nervous system.’’

(Id. at 28). The policy states that ‘‘[a]s 

a matter of science policy, blood 

cholinesterase data are considered 

appropriate surrogate measures of 

potential effects on peripheral nervous 

system acetylcholinesterase activity in 

animals, for central nervous system 

(‘‘CNS’’) acetylcholinesterase activity in 

animals when CNS data are lacking and 

for both peripheral and central nervous 

system acetylcholinesterase in 

humans.’’ (Id. at 29). The policy notes 

that ‘‘there is often a direct relationship 

between a greater magnitude of 

exposure [to a cholinesterase-inhibiting 

pesticide] and an increase in incidence 

and severity of clinical signs and 

symptoms as well as blood 

cholinesterase inhibition.’’ (Id. at 30). 

Thus, the policy regards blood 

cholinesterase data as ‘‘appropriate 

endpoints for derivation of reference 

doses or concentrations when 

considered in a weight-of-the-evidence 

analysis of the entire database ....’’ (Id. 

at 29). Between cholinesterase 

inhibition measured in red blood cell 

(‘‘RBC’’) or blood plasma, the policy 

states a preference for reliance on RBC 

acetylcholinesterase measurements 

because plasma is composed of a 

mixture of acetylcholinesterase and 

butyrylcholinesterase, and inhibition of 

the latter is less clearly tied to inhibition 

of acetylcholinesterase in the nervous 

system. (Id. at 29, 32). 

If a measure of cholinesterase 

inhibition (e.g., RBC cholinesterase) is 

being considered as a potential adverse 

effect or surrogate for an adverse effect, 

the policy advises that the level of 

inhibition must be critically evaluated 

‘‘in the context of both statistical and 

biological significance.’’ (Id. at 37) 

(emphasis in Original). The policy notes 

that ‘‘[n]o fixed percentage of change 

(e.g., 20% for cholinesterase enzyme 

inhibition) is predetermined to separate 

adverse from non-adverse effects.’’ (Id.). 

Rather, the policy explains that ‘‘OPP’s 

experience with the review of toxicity 

studies with cholinesterase-inhibiting 

substances shows that differences 

between pre- and post-exposure of 20% 

or more in enzyme levels is nearly 

always statistically significant and 

would generally be viewed as 

biologically significant.’’ (Id. at 37-38). 

The policy recommends that ‘‘[t]he 

biological significance of statisticallysignificant changes of less than 20% 

would have to be judged on a case-bycase basis, noting, in particular the 

pattern of changes in the enzyme levels 

and the presence or absence of 

accompanying clinical signs and/or 

symptoms.’’ (Id. at 38). The policy notes 

that similar or higher levels of 

cholinesterase inhibition are used ‘‘in 

monitoring workers for occupational 

exposures (even in the absence of signs, 

symptoms, or other behavioral effects).’’

(Id. at 31). For example, the policy 

points out that the California 

Department of Health Services requires 

that workers exposed to toxic chemicals 

such as organophosphate pesticides be 

removed from the workplace if ‘‘red 

blood cell cholinesterase levels show 

30% or greater inhibition,’’ and that the 

World Health Organization ‘‘has 

guidelines with the same RBC action 

levels (i.e., 30% or greater inhibition).’’

(Id.). 

C. Endocrine Disruptor Screening 

Program 

The 1996 FQPA and SWDA 

amendments directed EPA to develop 

and implement an endocrine screening 

program. To aid in the design of this 

program called for in the FQPA and 

SDWA amendments, EPA created the 

Endocrine Disruptor Screening and 

Testing Advisory Committee 

(‘‘EDSTAC’’), which was comprised of 

members representing the commercial 

chemical and pesticides industries, 

federal and state agencies, worker 

protection and labor organizations, 

environmental and public health 

groups, and research scientists. (63 FR 

71542, 71544, Dec. 28, 1998). The 

EDSTAC presented a comprehensive 

report in August 1998 addressing both 

the scope and elements of the endocrine 

screening program. (Ref. 11). The 

EDSTAC’s recommendations were 

largely adopted by EPA. 

As recommended by EDSTAC, EPA 

expanded the scope of the program from 

focusing only on estrogenic effects to 

include other effects on the endocrine 

system (i.e., androgenic and thyroid 

effects). (63 FR at 71545). Further, EPA, 

again on the EDSTAC’s 

recommendation, chose to include both 

human and ecological effects in the 

program. (Id.). Finally, based on 

EDSTAC’s recommendation, EPA 

established the universe of chemicals to 

be screened to include not just 

pesticides but also a wide range of other 

chemical substances. (Id.). As to the 

program elements, EPA adopted 

EDSTAC’s recommended two-tier 

approach with the first tier involving 

screening ‘‘to identify substances that 

have the potential to interact with the 

endocrine system’’ and the second tier 

involving testing ‘‘to determine whether 

the substance causes adverse effects, 


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identify the adverse effects caused by 

the substance, and establish a 

quantitative relationship between the 

dose and the adverse effect.’’ (Id.). Tier 

1 screening is limited to evaluating 

whether a substance is ‘‘capable of 

interacting with’’ the endocrine system, 

and is ‘‘not sufficient to determine 

whether a chemical substance may have 

an effect in humans that is similar to an 

effect produced by naturally occurring 

hormones.’’ (Id. at 71550). Based on the 

results of Tier 1 screening, EPA will 

decide whether Tier 2 testing is needed. 

Importantly, ‘‘[t]he outcome of Tier 2 is 

designed to be conclusive in relation to 

the outcome of Tier 1 and any other 

prior information. Thus, a negative 

outcome in Tier 2 will supersede a 

positive outcome in Tier 1.’’ (Id. at 

71554-71555). 

The EDSTAC provided detailed 

recommendations for Tier 1 screening 

and Tier 2 testing. The panel of the 

EDSTAC that devised these 

recommendations was comprised of 

distinguished scientists from academia, 

government, industry, and the 

environmental community. (Ref. 11 at 

Appendix B). As suggested by the 

EDSTAC, EPA has proposed a battery of 

short-term in vitro and in vivo assays for 

the Tier 1 screening exercise. (63 FR at 

71550-71551). Validation of all but one 

of these assays is complete. As to Tier 

2 testing, EPA, on the recommendation 

of the EDSTAC, has proposed using five 

longer-term reproduction studies that, 

with one exception, ‘‘are routinely 

performed for pesticides with 

widespread outdoor exposures that are 

expected to affect reproduction.’’ (Id. at 

71555). EPA is examining, pursuant to 

the suggestion of the EDSTAC, 

modifications to these studies to 

enhance their ability to detect endocrine 

effects. 

EPA has published a draft list of the 

first group of chemicals that will be 

tested under the Agency’s endocrine 

disruptor screening program. (72 FR 

33486 (June 18, 2007)). The draft list 

was produced based solely on the 

exposure potential of the chemicals and 

EPA has emphasized that ‘‘[n]othing in 

the approach for generating the initial 

list provides a basis to infer that by 

simply being on this list these chemicals 

are suspected to interfere with the 

endocrine systems of humans or other 

species, and it would be inappropriate 

to do so.’’ (Id.) 

D. EPA’s Human Research Rule 

EPA decisions regarding the ethics of 

human studies are governed by the 

Protection for Subjects in Human 

Research final rule (‘‘Human Research 

rule’’), which significantly strengthened 

and expanded protections for subjects of 

human research. (71 FR 6138 (February 

6, 2006)). The framework of the Human 

Research rule rests on the basic 

principle that EPA will not, in its 

actions, rely on data derived from 

unethical research. The rule divides 

studies involving intentional dosing of 

human subjects into two groups: ‘‘new’’

studies - those initiated after April 7, 

2006 (the effective date of the rule) - and 

‘‘old’’ studies - those initiated before 

April 7, 2006. The Human Research 

Rule forbids EPA from relying on data 

from any ‘‘new’’ study, unless EPA has 

adequate information to determine that 

the research was conducted in 

substantial compliance with the ethical 

requirements contained therein. (40 

CFR. 26.1705). These ethical rules are 

derived primarily from the ‘‘Common 

Rule,’’ (40 CFR part 26), a rule setting 

ethical parameters for studies conducted 

or supported by the federal government. 

In addition to requiring informed 

consent and protection of the safety of 

the subjects, among other things, the 

rule specifies that ‘‘[r]isks to subjects 

[must be] reasonable in relation to . . . 

the importance of the knowledge that 

may reasonably be expected to result 

[from the study].’’ (40 CFR 

26.1111(a)(2)). In other words, a study 

would be judged unethical if it did not 

have scientific value outweighing any 

risks to the test subjects. 

As to ‘‘old’’ studies, the Human 

Research Rule forbids EPA from relying 

on such data if there is clear and 

convincing evidence that the conduct of 

the research was fundamentally 

unethical or significantly deficient with 

respect to the ethical standards 

prevailing at the time the research was 

conducted. (40 CFR 26.1704). EPA has 

indicated that in evaluating ‘‘the ethical 

standards prevailing at the time the 

research was conducted’’ it will 

consider the Nuremburg Code, various 

editions of the Declaration of Helsinki, 

the Belmont Report, and the Common 

Rule, as among the standards that may 

be applicable to any particular study. 

(71 FR at 6161). Further, reflecting the 

concern that scientifically invalid data 

are ‘‘always unethical,’’ (71 FR at 6160), 

the rule limits the human research that 

can be relied upon by EPA to 

‘‘scientifically valid and relevant data.’’

(40 CFR 26.1701). 

Whether the data are ‘‘new’’ or ‘‘old,’’

the Human Research rule forbids EPA 

from relying on data from any study 

involving intentional exposure of 

pregnant women, fetuses, or children 

subject to a very limited exception. (40 

CFR 26.1703, 1706). 

To aid EPA in making scientific and 

ethical determinations under the 

Human Research rule, the rule 

established an independent Human 

Studies Review Board (‘‘HSRB’’) to 

review both proposals for new research 

(‘‘new’’ studies) and reports of 

completed human research (‘‘old’’

studies) on which EPA proposes to rely. 

(40 CFR 26.1603). The rule directs that 

HSRB shall be comprised of non-EPA 

employees ‘‘who have expertise in fields 

appropriate for the scientific and ethical 

review of human research, including 

research ethics, biostatistics, and human 

toxicology.’’ (40 CFR 26.1603(a)). If EPA 

decides to rely on the results from ‘‘old’’

research conducted to identify or 

measure a toxic effect, EPA must submit 

the results of its assessment to the HSRB 

for evaluation of the ethical and 

scientific merit of the research. (40 CFR 

26.1602(b)(2)). 

EPA has established the HSRB as a 

federal advisory committee under the 

Federal Advisory Committee Act 

(‘‘FACA’’) to take advantage of ‘‘the 

benefits of the transparency and 

opportunities for public participation’’

that accompany a FACA committee. (71 

FR at 6156). The HSRB, as appointed by 

EPA, contains approximately 16 

distinguished experts in the fields of 

bioethics, biostatistics, human health 

risk assessment and human toxicology, 

primarily from academia. (Ref. 12). 

NRDC and other parties have 

challenged the legality of the Human 

Research rule. (NRDC v. U.S. EPA, No. 

06-0820-ag (2d Cir.)). A decision on this 

challenge is presently pending before 

the United States Court of Appeals for 

the Second Circuit. 

IV. Regulatory History of DDVP 

A. In General 

1. DDVP use. Dichlorvos (2, 2- 

dichlorovinyl dimethyl phosphate), also 

known as DDVP, is an insecticide used 

in controlling flies, mosquitoes, gnats, 

cockroaches, fleas, and other insect 

pests. (Ref. 3). DDVP is registered for 

use on agricultural sites; commercial, 

institutional, and industrial sites; and 

for domestic use in and around homes. 

Agricultural and other commercial uses 

include in greenhouses; mushroom 

houses; storage areas for bulk, packaged 

and bagged raw and processed 

agricultural commodities; food 

manufacturing/processing plants; 

animal premises; and non-food areas of 

food-handling establishments. It is also 

registered for treatment of cattle, poultry 

and swine. DDVP is not registered for 

direct use on any field grown 

commodities. Currently, there are 27 

tolerances listed in 40 CFR 180.235 for 

DDVP on agricultural (food and feed) 

crops and animal commodities. DDVP is 


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applied with aerosols, fogging 

equipment, and spray equipment, and 

through use of impregnated materials 

such as resin strips which result in slow 

release of the pesticide. The current 

registrant for the technical active 

ingredient, DDVP, is Amvac Chemical 

Corporation (‘‘Amvac’’). 

2. DDVP risks. The following 

information on the assessment of the 

risks posed by DDVP is drawn from 

EPA’s decision on the reassessment of 

DDVP tolerances and its response to 

NRDC’s petition. 

DDVP is a chlorinated 

organophosphate pesticide which 

inhibits plasma, RBC, and brain 

cholinesterase in a variety of species. 

(Ref. 3 at 122-123). Subchronic and 

chronic oral DDVP exposures to rats and 

dogs as well as chronic inhalation DDVP 

exposure to rats resulted in significant 

decreases in plasma, RBC and/or brain 

cholinesterase activity. However, DDVP 

does not cause delayed neurotoxicity in 

the hen. Repeated, oral subchronic 

DDVP exposures in male humans were 

associated with statistically and 

biologically significant decreases in RBC 

cholinesterase inhibition. There was no 

evidence of increased susceptibility to 

young animals following in utero DDVP 

exposure to rat and rabbit fetuses as 

well as pre/post natal DDVP exposure to 

rats in developmental, reproduction, 

and comparative cholinesterase studies. 

Evidence of sensitivity in the young was 

seen in one parameter, auditory startle 

amplitude, in a developmental 

neurotoxicity study; however, the 

effects in the rat pups here was at levels 

well above levels which result in RBC 

cholinesterase inhibition. Cancer 

studies with DDVP provide suggestive 

evidence of DDVP’s potential human 

carcinogenicity; however, following the 

advice of numerous independent 

scientific panels, EPA has determined 

that DDVP poses a negligible cancer risk 

to humans due to the lack of relevance 

to humans of the tumors identified in 

the DDVP cancer studies. (72 FR at 

68671-68673). 

Inhibition of cholinesterase activity 

was the toxicity endpoint selected to 

assess hazards for all acute and chronic 

dietary exposures, as well as short-, 

intermediate-, and long-term (chronic) 

dermal, inhalation, and incidental oral 

residential exposures. Doses selected for 

the Point of Departure in determining 

the level of concern - i.e., RfD/PADs and 

acceptable MOEs - were based on both 

human and animal studies. (Ref. 3 at 

130-135). 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 

was used evaluating risk from shortterm incidental oral exposure; short-, 

intermediate-, and long-term dermal 

exposure; and short- and intermediateterm inhalation exposure. 

Safety factor determinations used in 

selecting the level of concern differed 

based on whether EPA relied on one of 

several different animal studies or a 

human study. 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 intrahuman variability). EPA removed the 

10X children’s safety factor for risk 

assessments based on an animal study. 

For levels of concerns derived from a 

Point of Departure from the human 

study, EPA applied a 10X safety factor 

for intra-human variability and a 3X 

children’s safety factor. (Id.). 

EPA based its decision to remove the 

children’s safety factor when relying on 

animal data on its conclusions that (1) 

the toxicity database was complete; (2) 

most of the data indicated no sensitivity 

in the young and the only evidence of 

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 

DDVP was not understated. EPA 

retained a portion of the children’s 

safety factor when relying on the human 

study because that study did not 

determine a NOAEL. EPA concluded, 

however, that reliable data supported 

reduction of the 10X factor because the 

effect seen at the LOAEL in that study 

was so marginal that a lower dose 

would have been unlikely to detect any 

adverse effect. (72 FR 68694-68695). 

EPA has estimated exposure to DDVP 

taking into account the potential for 

DDVP residues in food, drinking water, 

and in the home as the result of the use 

of DDVP pest strips. DDVP exposure 

may result not only from use of DDVP 

but use of two closely-related pesticides, 

naled and trichlorfon, which metabolize 

or degrade to DDVP in food, water, or 

the environment. In assessing the risks 

of DDVP, EPA has taken into account 

exposure to DDVP resulting from use of 

all three of these pesticides. (Ref. 3 at 

147-149). Additionally, DDVP, naled, 

and trichlorfon are within a family of 

pesticides known as the 

organophosphates. EPA has classified 

the organophosphate pesticides and 

their common cholinesterase-inhibiting 

degradates as having a common 

mechanism of toxicity. Thus, in 

addition to assessing the risks posed by 

exposure to organophosphate pesticides 

individually, EPA has assessed the 

potential cumulative effects from 

concurrent exposure to 

organophosphate pesticides. (Ref. 13). 

As discussed in Unit IV.B.1. below, 

taking all of the above information into 

account, EPA concluded that the 

tolerances for DDVP were safe. 

B. FFDCA Tolerance Reassessment and 

FIFRA Pesticide Reregistration 

1. In general. As required by the 

FQPA of 1996, EPA reassessed the 

safety of the DDVP tolerances under the 

new safety standard established in the 

FQPA. EPA released for comment a 

preliminary risk assessment for DDVP in 

October, 2000. (65 FR 60430 (October 

11, 2000)). Subsequently, after 

consideration of public comment, EPA, 

on June 30, 2006, issued an Interim 

Reregistration Eligibility Document 

(‘‘IRED’’) for DDVP. In that document, 

EPA determined that aggregate exposure 

to DDVP as a result of use of DDVP, 

naled, and trichlorfon, complied with 

the FQPA safety standard. (Ref. 3 ). 

Separately, on July 31, 2006, EPA 

determined that cumulative ffects from 

exposure to all organophosphate 

residues were safe. (Ref. 14). In 

combination, these findings satisfied 

EPA’s obligation to review the DDVP 

tolerances under the new safety 

standard. 

As a result of the FIFRA reregistration 

and FFDCA tolerance reassessment 

process there were numerous changes 

made to DDVP’s registration that affect 

non-occupational exposure to DDVP. 

Specifically, on May 9, 2006, EPA 

received from Amvac, the only 

registrant of DDVP as a product for 

manufacturing end-use DDVP products, 

an irrevocable request to cancel certain 

uses and include additional pest strip 

label restrictions on the DDVP active 

ingredient product labels. Pursuant to 

section 6(f) of FIFRA, on June 30, 2006, 

the Agency published a notice in the 

Federal Register that it had received the 

request and sought comment on EPA’s 

intention to grant the request and cancel 

the specified uses. (71 FR 37570 (June 

30, 2006)). On October 20, 2006, EPA 

issued the final cancellation order. (71 

FR 61968 (October 20, 2006)). 

The added restrictions on the use of 

the pest strip products were approved 

on October 11, 2006, and provided, 

among other things, that large pest strips 

could no longer be used in homes 

except for garages, attics, crawl spaces, 

and sheds that are occupied for less 

than 4 hours per day. The only pest 

strips permitted for use in occupied 

areas inside the home were significantly 

smaller strips for use in closets, 

wardrobes, or cupboards. Additionally, 

in early March, 2007, Amvac requested 

the voluntary cancellation of all its pet 


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collar and bait registrations and deletion 

of those uses from its technical label. 

Pursuant to section 6(f) of FIFRA, 

Amvac’s requests to cancel the pet 

collar and bait registrations as well as 

deleting such uses from the technical 

label were published in the Federal 

Register on March 23, 2007. (72 FR 

13786 (March 23, 2007)). On June 27, 

2007, EPA issued the final cancellation 

notice for the pet collar and bait 

registrations. (72 FR 35235 (June 27, 

2007)). 

Cancellation of uses and label 

restrictions imposed on Amvac’s 

registration apply to all formulated 

DDVP end-use products because it is 

unlawful to use a pesticide in a manner 

inconsistent with its label. (7 U.S.C. 

136(ee)). This bar on use inconsistent 

with the label applies to the formulation 

of end-use pesticide products from 

manufacturing use products. 

Accordingly, because Amvac holds the 

only registration for a DDVP 

manufacturing use product, the removal 

of uses and the addition of restrictions 

with respect to Amvac’s manufacturing 

use product label has the effect of 

imposing those use cancellations and 

label restrictions on all DDVP end-use 

products. 

2. Review of human study. 

Completion of the DDVP IRED was 

delayed, in part, by questions regarding 

whether it was appropriate for EPA to 

rely on several human toxicity studies 

conducted with DDVP which were 

submitted by Amvac. The study 

receiving principal attention was a 

study involving repeated dosing over 

several days conducted in 1997 by A.J. 

Gledhill. (Refs. 3 at 133; and 15). That 

study is identified by the Master Record 

Identification (‘‘MRID’’) number of 

44248801. Amvac also cited 

approximately a dozen other human 

studies, several of which were also 

conducted by Gledhill. (Ref. 16). 

Following promulgation of the 

Human Research rule, EPA evaluated 

whether the human data submitted by 

Amvac complied with the rule, and, 

pursuant to the rule’s requirements, 

presented these data and its 

recommendations to the Human Studies 

Review Board (‘‘HSRB’’) for review. On 

March 9, 2006, the HSRB published a 

notice in the Federal Register 

announcing that a public meeting would 

be held to consider the DDVP studies as 

well as human studies for several other 

pesticides. (71 FR 12194 (March 9, 

2006)). The meeting was scheduled for 

April 4-6, 2006. The notice alerted the 

public of the opportunity to file both 

written comments with the HSRB and to 

make oral comments at the April 

meeting. The members of the HSRB at 

the time of this meeting are listed in 

Appendix 1. 

NRDC filed written comments with 

the HSRB concerning DDVP, (Ref. 17), 

and also presented oral testimony at the 

public meeting. (Ref. 18). NRDC’s 

comments and oral remarks specifically 

focused on whether the Gledhill study 

had sufficient statistical power ‘‘to 

detect an effect when it may occur’’ and 

the fact that the Gledhill study only 

used healthy, male test subjects. (Ref. 7 

at 13). Other subjects discussed at the 

meeting included the relative strengths 

and weaknesses of the Gledhill study 

such as its repeat dosing regime, the 

failure to test blood plasma 

cholinesterase, the failure to monitor 

subjects after testing, and the study’s 

consent form. (Id.; Ref. 18 at 18, 20-23). 

On May 23, 2006, the HSRB published 

a notice in the Federal Register alerting 

the public that it had released a draft 

report (dated May 16, 2006) and would 

be holding a public teleconference 

meeting on June 6, 2006 to discuss its 

draft report. (71 FR 29624 (May 23, 

2006)). The notice included instructions 

on how members of the public could 

participate in the teleconference and 

explained the procedure for providing 

oral and written comments. (Ref. 19). 

NRDC did not file comments on the 

draft report. (Ref. 20). 

On June 26, 2006, the HSRB issued its 

finding that reliance on the Gledhill 

human study was appropriate given that 

the study had scientific value and there 

was no clear and convincing evidence 

that the study was fundamentally 

unethical. (Ref. 21). The HSRB 

concluded that the other DDVP human 

studies should not be used in the DDVP 

risk assessment. These findings were 

unchanged from its May 16, 2006 draft 

report. 

EPA agreed with the findings of the 

HSRB and relied upon the HSRB’s 

reasoning in using the Gledhill study in 

its DDVP risk assessment. (72 FR at 

68675). 

V. NRDC Petition Regarding DDVP 

On June 2, 2006, the NRDC filed a 

petition with EPA which, among other 

things, requested that EPA: (1) Conclude 

the DDVP Special Review by August 3, 

2006, with a finding that DDVP causes 

unreasonable adverse effects on the 

environment; (2) conclude the DDVP 

FIFRA reregistration process by August 

3, 2006, with a finding that DDVP is not 

eligible for reregistration; (3) submit 

draft notices of intent to cancel all 

DDVP registrations to the FIFRA 

Scientific Advisory Panel and USDA by 

August 3, 2006, and issue those notices 

60 days thereafter; (4) conclude the 

DDVP tolerance reassessment process by 

August 3, 2006, with a finding that the 

DDVP tolerances do not meet the 

FFDCA safety standard; and (5) issue a 

final rule by August 3, 2006, revoking 

all DDVP tolerances. (Ref. 2). Shortly 

after the petition was filed, on June 30, 

2006, EPA released the IRED for DDVP 

which addressed DDVP’s eligibility for 

reregistration under FIFRA and 

assessed, in part, whether DDVP’s 

tolerances met the new safety standard 

enacted by the FQPA. NRDC submitted 

comments on the IRED and some of 

these comments bore on issues in its 

petition. (Ref. 3). 

NRDC’s petition contained dozens of 

claims as to why DDVP’s registration 

under FIFRA should be canceled and its 

FFDCA tolerances revoked. These issues 

are not presented in detail here because 

many raised solely FIFRA concerns and 

NRDC has not pursued most of its 

tolerance-related claims in its objections 

and hearing requests. 

EPA published notice of the petition 

for comment on October 11, 2006. (71 

FR 59784 (October 11, 2006)). EPA 

received roughly 1,500 brief comments 

in support of the petition. These 

comments added no new information 

pertaining to whether the tolerances 

were in compliance with the FFDCA. 

Detailed comments in opposition to the 

petition were submitted by Amvac. (Ref. 

22). 

EPA responded to the petition in 

three separate documents: (1) It issued 

an order closing out the DDVP Special 

Review; (72 FR 72709 (December 21, 

2007)); (2) it issued an order denying the 

request to cancel DDVP’s FIFRA 

registration (72 FR 68581(December 5, 

2007)); and (3) it issued an order 

pursuant to FFDCA section 408(d)(4)(iii) 

denying the request to revoke DDVP’s 

FFDCA tolerances (78 FR 68662 

(December 5, 2007). Today’s final order 

only concerns the objections filed to the 

section 408(d)(4)(iii) order denying the 

request to revoke tolerances. 

VI. EPA Response to the Petition to 

Revoke DDVP Tolerances 

EPA issued a section 408(d)(4)(iii) 

order responding to the petition’s 

request to revoke DDVP tolerances on 

December 5, 2007 (hereinafter referred 

to as EPA’s ‘‘petition response’’ or 

‘‘petition denial order’’). (72 FR 68662 

(December 5, 2005). That order denied 

the petition finding that none of the 

grounds asserted by NRDC 

demonstrated that the DDVP tolerances 

should be revoked. Nonetheless, EPA 

did conclude that NRDC raised several 

pertinent concerns with EPA’s 

assessment of the risks posed by DDVP. 

To respond to NRDC’s concerns, EPA 

completely revamped both its dietary 


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and residential risk assessments. In its 

new risk assessments, EPA included 

updated information on residue levels 

of DDVP in food, the amount of usage 

of DDVP and related pesticides in 

agriculture, and food consumption 

patterns of infants and children. EPA 

also adopted modified and more 

conservative assumptions regarding 

exposure patterns to DDVP in 

residential settings and exposure to 

DDVP from naled’s use to control 

mosquitoes. Because, however, EPA 

concluded that the revised risk 

assessments still showed that the DDVP 

tolerances are safe, EPA denied NRDC’s 

petition. 

EPA’s specific responses to the claims 

in the petition that are relevant to 

NRDC’s objections are summarized in 

the portion of this order responding to 

the objections and hearing requests. 

VII. NRDC’s Objections and Requests 

for Hearing 

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. 

As indicated above, NRDC’s objections 

and requests for hearing raise 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 

DDVP that was conducted with humans. 

NRDC cites three grounds for its 

assertion that EPA unlawfully lowered 

the 10X children’s safety factor: (1) that 

EPA lacked adequate data on DDVP’s 

potential effects on the endocrine 

system; (2) that EPA lacked adequate 

data on several matters related to 

assessing dietary exposure to DDVP 

residues in food; and (3) that EPA has 

inadequate data on exposure to DDVP 

from its use in residential pest strips. As 

to the DDVP human study, NRDC 

claimed that EPA’s regulation 

concerning use of human studies is 

unlawful and that the study is 

scientifically flawed and ethically 

compromised. In analyzing NRDC’s 

claims, EPA has broken NRDC’s two 

main claims down into 19 separate subissues. Each sub-issue is described in 

detail and responded to separately in 

Unit VIII. 

In support of its request for hearing, 

NRDC proffered the following 

documents as evidence that a hearing 

would be appropriate: 

(1) the Interim Reregistration Eligibility 

Determination for DDVP; (2) the entire record 

for the IRED and the documents referenced 

and cited therein; (3) NRDC’s comments on 

the IRED; (4) EPA’s petition denial and the 

references cited in that denial; (5) NRDC’s 

petition and all references cited in the 

petition; and (6) the arguments, citations, and 

attachments contained in these objections. 

(Ref. 1 at 3) (citations and references to 

attachments omitted). 

VIII. Response to Objections and 

Requests for Hearing 

A. Overview 

EPA denies each of NRDC’s objections 

as well as its hearing requests. NRDC’s 

hearing requests fail to meet the 

statutory and regulatory requirements 

for holding a hearing. NRDC has failed 

to proffer evidence on its hearing 

requests which would, if established, 

resolve one or more issues in its favor. 

Rather, NRDC relies on mere allegations 

and general denials and contentions. 

Further, many of NRDC’s claims do not 

present genuine and substantial issues 

of fact and/or are immaterial to the relief 

requested. On the merits, NRDC’s 

objections are denied for substantially 

the same reasons given in EPA’s petition 

denial order. NRDC’s objections largely 

restate the claims in its petition. 

Significantly, NRDC does not 

acknowledge or respond to the 

substantial revisions to the DDVP 

dietary and residential risk assessments 

made in response to the NRDC petition. 

Similarly, NRDC does not acknowledge 

or respond to EPA’s detailed summary 

of why it adopted the conclusion by the 

independent HSRB that the Gledhill 

human study complied with EPA’s 

Human Research rule. 

The remainder of this Unit is 

organized in the following manner. Unit 

VIII.B. describes in greater detail the 

requirements pertaining to when it is 

appropriate to grant a hearing request. 

Unit VIII.C. examines the evidence 

proffered by NRDC in support of its 

hearing requests. Units VIII.D. and E. 

provide EPA’s response to the NRDC’s 

objections and hearing requests. Unit 

VIII.D. addresses NRDC’s claims 

regarding the children’s safety factor 

and subunit E addresses NRDC’s 

arguments concerning reliance on the 

Gledhill human study. EPA’s 

conclusions on the hearing requests and 

objections are summarized in Units 

VIII.F. and G., respectively. 

EPA has adopted a 4-part format in 

Units VIII.D. and E. for explaining its 

ruling on each of the 19 sub-issues EPA 

identified in the objections. First, 

NRDC’s claim and any arguments or 

evidence tendered to support that claim 

are described. Second, background 

information on the claim is provided 

including whether and how the claim 

was presented in NRDC’s petition and, 

if it was presented, EPA’s reasons for 

denying the claim in its earlier petition 

denial order. Third, EPA explains its 

reasons for denying a hearing on that 

claim. Finally, EPA explains its reasons 

for denying the claim on the merits. 

B. The Standard for Granting an 

Evidentiary Hearing 

EPA has established regulations 

governing objections to tolerance 

rulemakings and tolerance petition 

denials and requests for hearings on 

those objections. (40 CFR Part 178; 55 

FR 50291 (December 5, 1990)). Those 

regulations prescribe both the form and 

content of hearing requests and the 

standard under which EPA is to 

evaluate requests for an evidentiary 

hearing. 

As to the form and content of a 

hearing request, the regulations specify 

that a hearing request must include: (1) 

a statement of the factual issues on 

which a hearing is requested and the 

requestor’s contentions on those issues; 

(2) a copy of any report, article, or other 

written document ‘‘upon which the 

objector relies to justify an evidentiary 

hearing;’’ and (3) a summary of any 

other evidence relied upon to justify a 

hearing. (40 CFR 178.27). 

The standard for granting a hearing 

request is set forth in section 178.32. 

That section provides that a hearing will 

be granted if EPA determines that the 

‘‘material submitted’’ shows all of the 

following: 

(1) There is a genuine and substantial issue 

of fact for resolution at a hearing. An 

evidentiary hearing will not be granted on 

issues of policy or law. 

(2) There is a reasonable possibility that 

available evidence identified by the requestor 

would, if established, resolve one or more of 

such issues in favor of the requestor, taking 

into account uncontested claims or facts to 

the contrary. An evidentiary hearing will not 

be granted on the basis of mere allegations, 

denials, or general descriptions of positions 

and contentions, nor if the Administrator 

concludes that the data and information 

submitted, even if accurate, would be 

insufficient to justify the factual 

determination urged. 

(3) Resolution of the factual issue(s) in the 

manner sought by the person requesting the 

hearing would be adequate to justify the 

action requested. An evidentiary hearing will 

not be granted on factual issues that are not 

determinative with respect to the action 

requested. For example, a hearing will not be 

granted if the Administrator concludes that 

the action would be the same even if the 

factual issue were resolved in the manner 

sought. 

(40 CFR 178.32(b)). 

This provision essentially imposes 

four requirements upon a hearing 

requestor. First, the requestor must 

show it is raising a question of fact, not 


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one of law or policy. Hearings are for 

resolving factual issues not for debating 

law or policy questions. Second, the 

requestor must demonstrate that there is 

a genuine dispute as to the issue of fact. 

If the facts are undisputed or the record 

is clear that no genuine dispute exists, 

there is no need for a hearing. Third, the 

requestor must show that the disputed 

factual question is material - i.e., that it 

is outcome determinative with regard to 

the relief requested in the objections. 

Finally, the requestor must make a 

sufficient evidentiary proffer to 

demonstrate that there is a reasonable 

possibility that the issue could be 

resolved in favor of the requestor. 

Hearings are for the purpose of 

providing objectors with an opportunity 

to present evidence supporting their 

objections; as the regulation states, 

hearings will not be granted on the basis 

of ‘‘mere allegations, denials, or general 

descriptions of positions or 

contentions.’’ (40 CFR 178.32(b)(2)). 

EPA’s hearing request requirements 

are based heavily on FDA regulations 

establishing similar requirements for 

hearing requests filed under other 

provisions of the FFDCA. (53 FR 41126, 

41129 (October 19, 1988)). FDA 

pioneered the use of summary 

judgment-type procedures to limit 

hearings to disputed material factual 

issues and thereby conserve agency 

resources. FDA’s use of such procedures 

was upheld by the Supreme Court in 

1972, (Weinberger v. Hynson, Westcott 

& Dunning, Inc., 412 U.S. 609 (1973)), 

and, in 1975, FDA promulgated generic 

regulations establishing the standard for 

evaluating hearing requests. (40 FR 

22950 (May 27, 1975)). It is these 

regulations upon which EPA relied in 

promulgating its hearing regulations in 

1990. 

Unlike EPA, FDA has had numerous 

occasions to apply its regulations on 

hearing requests. FDA’s summary of the 

thrust of its regulations, which has been 

repeatedly published in the Federal 

Register in orders ruling on hearing 

requests over the last 24 years, is 

instructive on the proper interpretation 

of the regulatory requirements. That 

summary states: 

A party seeking a hearing is required to 

meet a ‘threshold burden of tendering 

evidence suggesting the need for a hearing.’

[] An allegation that a hearing is necessary to 

‘sharpen the issues’ or ‘fully develop the 

facts’ does not meet this test. If a hearing 

request fails to identify any evidence that 

would be the subject of a hearing, there is no 

point in holding one. 

A hearing request must not only contain 

evidence, but that evidence should raise a 

material issue of fact concerning which a 

meaningful hearing might be held. [] FDA 

need not grant a hearing in each case where 

an objection submits additional information 

or posits a novel interpretation of existing 

information. [] Stated another way, a hearing 

is justified only if the objections are made in 

good faith and if they ‘‘draw in question in 

a material way the underpinnings of the 

regulation at issue.’’ Finally, courts have 

uniformly recognized that a hearing need not 

be held to resolve questions of law or policy. 

(49 FR 6672, 6673 (February 22, 1984); 

72 FR 39557, 39558 (July 19, 2007) 

(citations omitted)). EPA has been 

guided by FDA’s application of its 

regulations in this proceeding. 

Congress confirmed EPA’s authority 

to use summary judgment-type 

procedures with hearing requests when 

it amended FFDCA section 408 in 1996. 

Although the statute had been silent on 

this issue previously, the FQPA added 

language specifying that when a hearing 

is requested, 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)). 

This language grants EPA broad 

discretion to determine whether a 

hearing is ‘‘necessary to receive factual 

evidence’’ to objections. 

C. Evidentiary Proffer by NRDC 

As noted above, the purpose for 

holding hearings is ‘‘to receive factual 

evidence.’’ (U.S.C. 346a(g)(2)(B); 53 FR 

41126, 41129 (‘‘Hearings are for the 

purpose of gathering evidence on 

disputed factual issues . . . .’’)). A 

requestor must identify evidence relied 

upon to justify a hearing and either 

submit copies of that evidence or 

summarize it. (40 CFR 178.27). After 

reviewing the proffer, EPA must find 

that there is a reasonable possibility that 

the proffered evidence, if established, 

would resolve one or more genuinelydisputed, material factual issues in a 

requestor’s favor. (40 CFR 178.32(b)). 

Because a substantial portion of NRDC’s 

evidentiary proffer is deficient on its 

face, EPA finds it most efficient to 

preliminarily review the proffer before 

turning to the individual issues raised 

by NRDC. 

As previously mentioned, NRDC 

proffered the following items as 

evidence supporting its requests for 

hearing: 

(1) the Interim Reregistration Eligibility 

Determination for DDVP; (2) the entire record 

for the IRED and the documents referenced 

and cited therein; (3) NRDC’s comments on 

the IRED; (4) EPA’s petition denial and the 

references cited in that denial; (5) NRDC’s 

petition and all references cited in the 

petition; and (6) the arguments, citations, and 

attachments contained in these objections. 

(Ref. 1 at 3). These items can be divided 

into two groups: (1) items produced or 

assembled by EPA (the IRED; the IRED 

record; and EPA’s petition denial); and 

(2) items produced by NRDC (NRDC’s 

comments on the IRED; NRDC’s 

petition; and NRDC’s objections). 

The items in the first group - the EPA 

documents - clearly do not constitute a 

proper proffer. Essentially, this is a nonspecific identification of every 

document and piece of data EPA has 

considered and relied upon in the 

multi-year process of conducting the 

FIFRA reregistration and FFDCA 

tolerance reassessment for DDVP and in 

responding to NRDC’s DDVP petition. 

This could easily encompass hundreds, 

if not thousands of documents, and tens 

of thousands of pages of analysis and 

data. EPA’s petition response alone 

cited 82 documents and those 

documents generally were EPA 

analytical papers and not the underlying 

data. EPA concludes that NRDC’s 

citation to the thousands of pages in the 

IRED, the IRED record, and the petition 

denial is so vague a proffer as to not 

constitute a proffer at all. It would be as 

if a lawyer, in responding to a court’s 

request for case law authority for a 

principle he or she was defending, cited 

the court to West’s Federal Reporter, 3rd 

Series. While somewhere in those 

hundreds of volumes a case may exist 

that supports the asserted principle, the 

lawyer cannot be said to have identified 

it by a vague wave at a substantial 

portion of the law library. Further, given 

that the purpose of a hearing is to gather 

or receive evidence, proffering evidence 

already considered and relied upon by 

EPA would not seem to be grounds for 

holding a hearing. Finally, as a matter 

of law, EPA does not understand how it 

can be argued that a proffer consisting 

of a general reference to a record of 

decision which EPA has found 

supported one result could constitute 

evidence that if established, would 

justify the opposite conclusion. At 

bottom, the proffer of the items in the 

first group fails to ‘‘identify’’ evidence 

which would, if established, resolve an 

issue in NRDC’s favor. 

NRDC’s second group of documents 

consists of NRDC’s comments on the 

IRED; NRDC’s petition; and NRDC’s 

objections. In analyzing this proffer, 

EPA has focused on NRDC’s objections 

because the objections appear to 

contain, almost word-for-word, the 

arguments and claims put forward in its 

petition and IRED comments with 

regard to the children’s safety factor and 

reliance on human studies. The 

objections reference 16 documents. For 

the reasons explained below, 10 of these 

documents can be rejected on their face 


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as not justifying a hearing. Four of the 

documents, however, potentially 

include factual evidence supporting a 

hearing and are analyzed more 

thoroughly in connection with the 

specific issue in the hearing request to 

which they are tied. The other two 

documents that are referenced are 

NRDC’s DDVP petition and NRDC’s 

comments on the DDVP IRED. As 

described above, these documents do 

not add anything beyond what is in the 

objections. 

1. Documents that clearly do not 

proffer evidence of a genuinelydisputed, material issue of fact. (10 

items) 

• Five Newspaper Stories. NRDC cites 

to an Associated Press story from 2002 

and four Los Angeles Times stories from 

2007. These news stories contain basic 

background information about DDVP; 

general contentions from Amvac, NRDC, 

and EPA regarding the safety of DDVP; 

and no more than a cursory, passing 

reference to any of the issues raised in 

the petition. There can be no serious 

contention that these articles present 

evidence justifying a hearing. 

• NRDC comments to HSRB. NRDC 

references the comments it submitted to 

the HSRB with regard to the HSRB’s 

review of the human studies conducted 

with DDVP. The comments - three pages 

of bulleted talking points and one graph 

- are a summary of the slightly more 

detailed arguments contained in NRDC’s 

objections. This document adds no 

justification for a hearing not otherwise 

included in NRDC’s objections. 

2. Legal Briefs in NRDC v. EPA, No. 

06-0820-ag (2d Cir.). NRDC cites to its 

opening and reply briefs in NRDC v. 

EPA, the case adjudicating NRDC’s 

challenge to EPA’s Human Research 

rule. These briefs contain legal 

arguments regarding the lawfulness of 

the Human Research rule. They contain 

no factual evidence justifying NRDC’s 

DDVP hearing requests. 

• Three Law Review Articles. NRDC 

references: (1) a short article by a NRDC 

attorney summarizing his legal 

objections to EPA’s Human Research 

rule; (2) an article concerning EPA’s 

implementation of the FQPA; and (3) an 

article focusing on how tort law might 

be used to supplement the FQPA to 

protect children. None of these articles 

mention DDVP and no serious 

contention can be made that they 

provide factual evidence justifying a 

hearing. 

3. Documents which may present 

evidence of a genuinely-disputed, 

material issue of fact. (4 items) 

• Lockwood Articles. NRDC cites two 

articles by Dr. Alan Lockwood which 

discuss science and ethical issues with 

regard to several human intentional 

dosing studies involving pesticides. 

Several of the human studies addressed 

were DDVP studies, one of which is the 

Gledhill human study that is the focus 

of this proceeding. Whether the 

information presented in these articles 

supports NRDC’s hearing requests is 

examined in Unit VIII.E.3.a. 

• Sass Letters. NRDC cites two letters 

published in the journal Environmental 

Health Perspectives co-authored by Dr. 

Jennifer Sass of NRDC. These letters 

discuss science and ethical issues with 

regard to two human studies, including 

the DDVP human study in question in 

this proceeding. Whether the 

information presented in these letters 

supports NRDC’s hearing requests is 

examined in Unit VIII.E.3.a. 

D. Response to Specific Issues Raised in 

Objections and Hearing Requests - 

Children’s Safety Factor 

1. Failure to support children’s safety 

factor decision with DDVP-specific 

data— a. Objection/hearing request subissue. NRDC asserts that EPA, in 

choosing a 3X children’s safety factor 

for DDVP, did not rely on reliable data 

showing that such a factor was safe for 

infants and children because EPA’s 

choice of 3X ‘‘is not based on any data 

specific to DDVP.’’ (Ref. 1 at 5). NRDC’s 

argument is that EPA erred by not 

deriving a precise safety factor for DDVP 

but instead used a value that EPA 

considered to be half of the 10X safety 

factor. NRDC claims that ‘‘EPA could 

not have determined that ‘such margin’

[i.e., 3X] will be safe, when the 

replacement safety factor is simply a 

generic stand-in for EPA’s conclusion 

that ‘something less than 10X’ is 

enough.’’ (Id.). According to NRDC, EPA 

should have explained ‘‘what reliable 

data supports a 3X safety factor in 

particular, as opposed to 4X or some 

other number, for DDVP specifically.’’

(Id.). 

b. Background. Similar assertions 

were made in NRDC’s petition and its 

IRED comments. For example, the 

petition claimed that ‘‘[t]he Agency did 

not explain why it chose 3X as opposed 

to 4X or any other factor,’’ (Ref. 2 at 14), 

and the IRED comments asserted that 

there was a ‘‘complete lack of 

explanation’’ for EPA’s safety factor 

decisions. (Ref. 23 at 5). Both 

documents also alleged there were 

inadequacies in the toxicity and 

exposure databases. (Refs. 2 at 15, and 

38-41; and 23 at 8-9). 

In response to these claims by NRDC, 

EPA, in the petition response, 

comprehensively restated its reasoning 

for its decisions on the children’s safety 

factor for DDVP in the IRED. (72 FR at 

68694-68695). EPA noted that it had a 

complete toxicity database for DDVP 

and it carefully reviewed the evidence 

regarding the sensitivity of the young to 

DDVP and explained why an additional 

safety factor was not needed to protect 

infants and children. Further, EPA 

detailed why it had concluded that its 

exposure assessments would not 

understate human exposure to DDVP. 

For some DDVP risk assessments EPA 

chose to remove the children’s safety 

factor entirely, and for others EPA 

reduced the safety factor to 3X. EPA 

explained that it retained a 3X 

children’s safety for certain assessments 

because the toxicity study which was 

relied upon in conducting those risk 

assessments had not identified a ‘‘no 

adverse effect level’’ (‘‘NOAEL’’) in its 

subjects but rather only a ‘‘lowest 

adverse effect level’’ (‘‘LOAEL’’). 

Despite the failure to identify a NOAEL 

in the study, EPA concluded that ‘‘a 3X 

factor’’ would be more than adequate to 

identify a NOAEL based upon the slight 

adverse effect (marginal RBC 

cholinesterase inhibition in a human 

study) observed at the LOAEL.’’ (72 FR 

at 68695). EPA noted that an 

independent science review board had 

confirmed that lower doses were 

unlikely to produce a measurable effect. 

Finally, EPA explained why it chose 3X 

instead of 4X or some other value. (Id.). 

The petition response noted that ‘‘where 

the data does not warrant a full 10X, 

EPA generally does not attempt to 

mathematically derive a precise 

replacement safety factor because 

regulatory agencies’ traditional use of 

10X safety factors (upon which the 

FQPA safety factor was modeled) was 

based on rough estimates rather than 

detailed calculations. Instead, where a 

10X factor would clearly overstate the 

uncertainty, EPA simply applies a factor 

valued at half of 10X.’’ (Id.). EPA 

explained that it considers 3X to be half 

of 10X assuming a lognormal 

distribution of effects. (Id.). 

c. Denial of hearing request. In 

analyzing whether a hearing would be 

appropriate on this sub-issue, it is 

helpful to break the sub-issue down into 

three separate, but related, questions: (1) 

Whether EPA, in selecting a children’s 

safety factor lower than 10X, is required 

to justify with precision why it chose 

one factor over another; (2) whether 

EPA offered a justification for the 

children’s safety factor it chose; and (3) 

whether EPA relied upon DDVP specific 

information in choosing a safety factor 

or instead relied upon ‘‘generic 

assertions.’’ When broken down in this 

way, it is clear that none of these 

questions meets the standard for a 

hearing. 


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The first question is a pure question 

of law - does FFDCA section 408(c) 

require EPA to offer a reasoned 

explanation for its choice of a children’s 

safety factor, including an explanation 

as to why a different factor is not 

needed. A question of fact, not of law, 

is required to justify a hearing. (40 CFR 

178.32(b)(1)).The second and third 

questions fail to present a matter of 

genuinely-disputed facts because it is 

plain on the record that EPA did offer 

a reasoned justification for its decision 

and, in that justification, relied upon 

DDVP-specific facts. EPA’s petition 

response to NRDC’s 10X arguments laid 

out in careful detail information 

regarding the extent of the toxicity and 

exposure database on DDVP and the 

data bearing on DDVP’s effects on young 

animals. (72 FR at 68694-68695 

(discussing the completeness of the 

DDVP toxicity database, DDVP studies 

bearing on pre- and post-natal toxicity, 

and the basis for DDVP exposure 

estimates)). Further, NRDC proffers no 

evidence - because there is none to 

proffer - suggesting that EPA did not 

consider DDVP-specific information in 

making its children’s safety factor 

decision. Therefore, this question does 

not meet the standard for a hearing both 

because there are no genuinely-disputed 

facts and NRDC has proffered no 

evidence which, if established, could 

resolve this issue in its favor. 57 FR 

6667, 6672 (February 27, 1992) (‘‘A 

hearing must be based on reliable 

evidence, not on mere allegations or on 

information that is inaccurate and 

contradicted by the record.’’) 

d. Denial of objection. EPA agrees 

with NRDC that general principles of 

administrative law require it to provide 

a reasoned explanation for its decision 

on selection of a children’s safety factor. 

(Baltimore Gas & Electric Co. v. NRDC, 

462 U.S. 87, 103 (1983)). EPA disagrees 

with NRDC, however, to the extent it is 

suggesting that as part of this reasoned 

explanation for its selection of a 

children’s safety factor, EPA must show 

why it did not choose some other 

mathematical value. Rather, the statute 

imposes upon EPA, if it decides to vary 

from the presumptive 10X children’s 

safety factor, the burden to show that 

any ‘‘different’’ safety factor is safe. 

Once EPA has made that showing, its 

obligation to offer a reasoned 

explanation is complete. Because EPA 

offered a reasoned explanation as to 

why the children’s safety factors it 

chose protect the safety of infants and 

children, (72 FR 68694-68695), EPA 

denies NRDC’s objection on this point. 

As to the substance of EPA’s 

explanation of why it chose a 3X safety 

factor for certain DDVP risk 

assessments, NRDC claims that EPA 

erred because its choice of 3X is based 

on ‘‘a generic assertion not [] on any 

data specific to DDVP.’’ (Ref. 1 at 5). 

NRDC is wrong. The generic assertion 

NRDC mentions is EPA’s explanation of 

why 3X is half of 10X. EPA’s choice of 

3X, however, is not based on its 

conclusion that 3X is half of 10X but on 

the data in the DDVP human study at 

issue. As noted above, the petition 

response explained in detail that a full 

10X safety factor was not needed to 

address the uncertainty raised by the 

failure of the DDVP human study to 

identify a NOAEL. The effects seen in 

that study at the LOAEL were only 

marginally adverse at best, and 

therefore, EPA concluded that applying 

the full 10X safety factor (i.e., dividing 

the LOAEL by another factor of 10X in 

addition to the 10X factor for intrahuman variability) was more than was 

needed to address the lack of a NOAEL. 

The HSRB confirmed as much when it 

wrote: ‘‘because the decreased activity 

in RBC cholinesterase activity observed 

in this study was at or near the limit of 

what could be distinguished from 

baseline values, it was unlikely that a 

lower dose would produce a measurable 

effect in RBC cholinesterase activity.’’

(Ref. 21 at 41). 

EPA chose a safety factor of 3X for 

DDVP based on its conclusion that not 

only was 10X overprotective but that 3X 

would be protective given the results 

seen in the relevant DDVP study. (72 FR 

at 68695). As EPA concluded in the 

petition denial order: ‘‘a 3X safety factor 

would be more than adequate to identify 

a NOAEL based upon the slight adverse 

effect (marginal RBC cholinesterase 

inhibition in a human study) observed 

at the LOAEL.’’ (Id.). Generally, EPA 

uses a 3X safety factor as the default 

value when reducing a 10X safety factor. 

(Refs. 5 at 9-10, 26; and 24 at 4-40 - 4- 

41; ). A safety factor of 3X is deemed to 

be approximately half the value of a 

safety factor of an order of magnitude 

(10X). As EPA explained in the petition 

denial order: 

In choosing a safety factor in circumstances 

where the data does not warrant a full 10X, 

EPA generally does not attempt to 

mathematically derive a precise replacement 

safety factor because regulatory agencies’

traditional use of 10X safety factors (upon 

which the FQPA safety factor was modeled) 

was based on rough estimates rather than 

detailed calculations. Instead, where a 10X 

factor would clearly overstate the 

uncertainty, EPA simply applies a factor 

valued at half of 10X. In determining half of 

a 10X factor, EPA assumes that the 

distribution of effects within the range of a 

safety factor is distributed lognormally 

(which is generally the case for biological 

effects), and reduction of a lognormal 

distribution by half is equal to half a log 

(10-5) or approximately 3X. A lognormal 

distribution is a distribution which if plotted 

based on the logarithm of each of its values 

would yield a bell-shaped (normal) 

distribution but if plotted according to actual 

values would be skewed having a clumping 

of values along the vertical axis of the plot. 

(72 FR at 68695) (citations omitted). 

NRDC does not challenge EPA’s 

reasoning regarding whether the choice 

of 3X is justified based on the results of 

a DDVP-specific study and thus, the 

merits of EPA’s DDVP-specific 

reasoning is not here at issue. Rather, 

NRDC denies that EPA engaged in 

DDVP-specific reasoning in choosing 

3X. Because NRDC’s argument is 

contradicted on the face of the petition 

response, it is denied. 

2. Endocrine effects. As described 

below, NRDC claims that EPA cannot 

remove the children’s safety factor 

because it has not completed the 

endocrine screening program for DDVP 

under section 408(p) and because EPA 

has inadequate endocrine data for 

DDVP. Although NRDC did argue in its 

petition that EPA cannot make a safety 

finding without completing the 

endocrine screening program, it did not 

assert claims regarding endocrine data 

and the children’s safety factor. EPA has 

previously ruled that a petitioner may 

not raise new issues in filing objections 

to EPA’s denial of its Original petition. 

(72 FR 39318, 39324 (July 18, 2007) 

(‘‘The FFDCA’s tolerance revocation 

procedures are not some sort of ‘game,’

whereby a party may petition to revoke 

a tolerance on one ground, and then, 

after the petition is denied, file 

objections to the denial based on an 

entirely new ground not relied upon by 

EPA in denying the petition.’’)). 

Accordingly, NRDC’s objections and 

hearing requests as to the children’s 

safety factor and endocrine data are 

denied. 

Even if these claims were properly 

presented in these objections, for the 

reasons set forth below they neither 

entitle NRDC to a hearing nor justify the 

relief sought. 

a. Endocrine disruptor screening 

program—i. Objection/hearing request 

sub-issue. NRDC argues that EPA must 

retain the 10X children’s safety factor 

because EPA has not fulfilled its 

obligations under FFDCA section 408(p) 

to screen pesticides, including DDVP, 

for endocrine disruption potential. (Ref. 

1 at 5). Essentially, NRDC argues that 

EPA must retain the children’s safety 

factor for any pesticide until testing 

under the endocrine screening program 

is completed for that pesticide. 

ii. Background. In its petition, NRDC 

claimed that failure to conduct the 


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endocrine screening program for DDVP 

under section 408(p) made it impossible 

for EPA to conclude that the DDVP 

tolerances are safe. (Ref. 2 at 49). EPA 

responded to this argument by citing its 

denial of a petition to revoke various 

pesticide tolerances in which the claim 

was made that EPA could not remove 

the children’s safety factor if endocrine 

screening under section 408(p) had not 

been conducted. (72 FR at 68676). 

There, EPA concluded that the statute 

did not impose a mandatory bar upon 

removal of the children’s safety factor 

until completion of the endocrine 

screening program. (71 FR 43906, 43920 

(August 2, 2006)). EPA also found in 

responding to the prior petition that it 

had sufficient data on endocrine 

screening for the pesticide in question 

to make a safety finding. (71 FR at 

43920-43921). After analyzing the 

endocrine data for DDVP, EPA 

concluded that it had sufficient data to 

make a safety finding as to DDVP. (72 

FR at 68676 - 68677). 

iii. Denial of hearing request. The 

question of whether completion of the 

endocrine screening program under 

FFDCA section 408(p) is a mandatory 

prerequisite to removal of the children’s 

safety factor is a legal issue. A question 

of fact, not of law, is required to justify 

a hearing. (40 CFR 178.32(b)(1)). 

iv. Denial of objection. In response to 

a prior pesticide tolerance revocation 

petition, and objections filed as to EPA’s 

denial of that petition, EPA has already 

rejected the legal claim presented in this 

objection. (71 FR at 43920; 72 FR 39318, 

39327-39328 (July 18, 2007). After 

analyzing the statutory language, 

structure, and legislative history, EPA 

concluded that section 408(p) does not 

override the ‘‘clear and unmistakable 

language[] [in section 408(b)(2)(C)] 

grant[ing] EPA discretion to make a factbased determination of whether a safety 

factor different than the 10X default 

value is safe for children.’’ (71 FR at 

43920). EPA summarized its reasoning 

as follows: 

under section 408(b)(2)(C) EPA clearly has 

the discretion to determine, in any given 

case, whether it has reliable data to choose 

a factor different than the 10X default value. 

Not only is there no statutory language 

supporting the [petitioners’] argument in 

favor of automatic retention of the 10X until 

completion of the endocrine screening 

program but the legislative history is in no 

way supportive of construing the enactment 

of the program as intended to have such a 

dramatic impact. Further, since the 

enactment of the FQPA, EPA’s 

contemporaneous and consistent approach to 

the endocrine screening program has been to 

treat that information-gathering exercise as 

not imposing some type of statutorilyprescribed, automatic injunction barring 

removal of the children’s safety factor until 

completion of information-gathering under 

the program. 

(Id.). EPA also catalogued the extensive 

data requirements already in place for 

pesticides that produced information on 

a pesticide’s potential endocrine effects. 

(71 FR at 43920-43921). EPA concluded 

that ‘‘in many instances the totality of 

the information gleaned from current 

data required for pesticides used on 

food will make it possible to develop a 

meaningful weight-of-the-evidence 

determination on the potential of the 

pesticide to adversely affect the 

endocrine system.’’ (Id.). 

NRDC has done nothing more than 

state in a conclusory fashion that 

completion of endocrine screening 

under section 408(p) is necessary to a 

decision to remove the children’s safety 

factor. Accordingly, EPA denies this 

objection for the reasons stated in its 

previous two orders addressing this 

claim. (71 FR at 43920 - 43921; 72 FR 

at 39327-39328). 

b. DDVP endocrine data—i. 

Objection/hearing request sub-issue. In 

its objections, NRDC argues that EPA 

has inadequate data on endocrine effects 

to remove the children’s safety factor. 

As support for this argument NRDC 

asserts: (1) that the studies relied upon 

by EPA ‘‘were not designed to detect 

endocrine disruption . . . ;’’ and (2) that 

the two-generation rat reproduction 

study does not meet EPA’s 1998 

guideline for such studies and, given 

that the reproduction study did show 

endocrine effects, a ‘‘[p]roper 

histopathology in the two generation rat 

reproduction study could have revealed 

adverse effects at lower levels than’’ the 

levels at which cholinesterase inhibition 

was seen in DDVP studies. (Ref. 1 at 6). 

ii. Background. As noted above, 

NRDC’s petition argued that EPA could 

not make a safety finding for DDVP in 

the absence of data collected under the 

section 408(p) screening program. EPA 

responded to this claim by examining 

the data on DDVP bearing on its 

potential endocrine effects. EPA 

concluded that it could make a safety 

finding for DDVP in absence of further 

endocrine data given that: ‘‘(1) data 

bearing on potential endocrine effects 

from a two-generation reproduction 

study as well as other chronic data in 

which effects on reproductive organs 

were examined; (2) EPA well 

understands DDVP’s most sensitive 

mechanism of toxicity (cholinesterase 

inhibition); and (3) the potential 

endocrine-related effects seen for DDVP 

appeared in the presence of significant 

cholinesterase inhibition and at levels 

nearly two orders of magnitude above 

the most sensitive cholinesterase effects. 

. . .’’ (72 FR at 68677). 

iii. Denial of hearing request. A 

hearing on this sub-issue is not 

appropriate because NRDC’s request is 

based on mere allegations, general 

contentions, and speculation. NRDC 

claims that the studies EPA relied upon 

were not ‘‘designed’’ to investigate 

endocrine effects; however, NRDC 

proffers no evidence to support such an 

allegation. Further, such a claim has 

little, if any, materiality, given that the 

important question is not whether the 

studies were ‘‘designed’’ to measure 

endocrine effects but whether they 

actually measure such effects. Notably, 

NRDC does not, and cannot upon this 

record, make the latter contention. (See 

72 FR at 68676 (discussing the 

numerous endocrine-related endpoints 

assessed in the DDVP database)). 

Further, NRDC’s claim that if the DDVP 

two-generation rat reproduction study 

had been conducted pursuant to the 

1998 guidelines it might have shown 

endocrine effects at lower doses than 

the doses at which DDVP’s 

cholinesterase effects were seen is 

nothing more than speculation. In 

applying its hearing regulations, FDA 

has routinely denied hearings on 

speculation about what redoing a study 

might show. For example, in a 

proceeding establishing a food additive 

regulation for acesulfame potassium, 

FDA denied a hearing to an objector 

who challenged FDA’s rejection of a 

study for only containing partial 

histopathological data. (57 FR 6667 

(February 27, 1992)). The objector had 

argued that full histopathological data 

might have altered FDA’s conclusion. 

FDA found such an argument 

unconvincing: ‘‘Because complete 

histopathological examination of tissues 

from all animals in the first rat study 

was not done and cannot be done now, 

any prediction of the results of such an 

examination is simply speculation. 

Speculation regarding data that do not 

exist cannot serve as the basis for a 

hearing.’’ (Id. at 6671). For all of the 

above reasons, the hearing request on 

this sub-issue is denied. 

iv. Denial of objection. EPA denies 

NRDC’s objection that EPA does not 

have adequate endocrine data on DDVP 

to remove the children’s safety factor. 

First, NRDC is wrong to imply that 

existing, required toxicity studies do not 

provide valuable information on 

potential endocrine effects. EPA 

discussed this issue in detail in an 

earlier order involving similar claims 

concerning a different pesticide. There, 

EPA pointed out that: 

The primary proposed Tier 2 study [for the 

Endocrine Disruptor Screening Program] 


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relevant to endocrine effects on humans is 

the 2-generation reproductive toxicity study 

in rats. This is one of the core studies 

required for all food-use pesticides since 

1984. In this reproduction study, potential 

hormonal effects can be detected through 

behavioral changes, ability to become 

pregnant, duration of gestation, signs of 

difficult or prolonged parturition, apparent 

sex ratio (as ascertained by anogenital 

distances) of the offspring, feminization or 

masculinization of offspring, number of 

pups, stillbirths, gross pathology and 

histopathology of the vagina, uterus, ovaries, 

testis, epididymis, seminal vesicles, prostate, 

and any other identified target organs. In fact, 

EPA, in 1998, in discussing this study’s use 

in Tier 2, identified 39 endpoints examined 

in this study relevant to estrogenic, 

androgenic, or thyroid effects. At that time, 

EPA noted that it was evaluating whether to 

add another 10 endocrine-related endpoints 

to the study protocol to enhance the utility 

of the study to detect endocrine effects. 

Despite the ongoing evaluation of additional 

endpoints, EPA has concluded that the 

existing 2-generation mammalian assay is 

valid for the identification and 

characterization of reproductive and 

developmental effects, including those due to 

endocrine disruption, based on the long 

history of its use, the endorsement of the 

1998 test guideline by the FIFRA Scientific 

Advisory Panel, and acceptance by member 

countries of the Organizations for Economic 

Cooperation and Development (OECD). 

(71 FR 43906, 43921 (August 2, 2006) 

(citations omitted)). That order also 

catalogued the numerous endocrinerelated endpoints in other chronic 

toxicities routinely-required for 

pesticides used on agricultural 

commodities. (Id.). 

Specifically as to DDVP, in its 

response to NRDC’s petition, EPA 

detailed four long-term DDVP toxicity 

studies, submitted under EPA data 

requirements that provided data on 

numerous effects that are relevant to 

potential endocrine disruption. EPA 

wrote: 

EPA has adequate data on DDVP’s 

potential endocrine effects to evaluate 

DDVP’s safety. In the 1989 NTP cancer 

studies with rats and mice, male and female 

reproductive organs (prostate, testes, 

epididymis, ovaries, uterus) were examined 

and no changes attributable to DDVP were 

found. The 52–week dog study with DDVP 

also was without effect in the reproductive 

organs (testes, prostate, epididymides, cervix, 

ovaries, uterus, vagina). EPA also has a 1992 

two-generation rat reproduction study with 

DDVP (via drinking water) that is similar to 

the most recent guidelines (1998) for conduct 

of such a study with respect to endocrinerelated endpoints. Although that study did 

not include certain evaluations that the 1998 

guidelines recommended related to 

endocrine-related effects (age of vaginal 

opening and preputial separation), it did 

incorporate other aspects of the 1998 

guidelines such as an examination of 

esterous cycling in females and sperm 

number, motility, and morphology in males. 

The study did identify an adverse effect on 

esterous cycling in females but only at the 

high dose (8.3 mg/kg/day). All doses in the 

study showed significant cholinesterase 

inhibition. Further, the NOAEL and LOAEL 

from the esterous cycling endpoint in the 

reproduction study are nearly two orders of 

magnitude higher than the NOAEL and 

LOAEL used as a Point of Departure in 

setting the chronic RfD/PAD for DDVP. 

(72 FR at 68676 (citations omitted). 

Further, the petition response 

additionally discussed a DDVP study 

from the scientific literature examining 

endocrine-related effects. (Id.). 

NRDC’s speculation - that further 

testing of DDVP might reveal endocrine 

effects at levels below those at which 

cholinesterase inhibition has been 

measured - does not convince EPA that 

there is not a reliable basis for removing 

the children’s safety factor as regards 

endocrine effects. As EPA indicated in 

its denial of the NRDC petition, it has 

several studies addressing numerous 

endpoints bearing on DDVP’s potential 

endocrine effects, DDVP’s 

cholinesterase inhibition effects are 

well-defined by existing data, and the 

only endocrine effect seen in the DDVP 

data occurred in the presence of 

significant cholinesterase inhibition and 

at a level two orders of magnitude (i.e., 

100X) greater than the level at which the 

most sensitive cholinesterase effects 

were seen. As a pesticide, DDVP is 

subject to testing under the endocrine 

disruptor screening program; however, 

EPA expects that that data will confirm 

its conclusion regarding DDVP’s 

potential endocrine effects. NRDC’s 

objection on this point is denied. 

3. Dietary exposure—a. Objection/ 

hearing request sub-issue. NRDC claims 

that there are numerous uncertainties in 

EPA’s estimate of dietary exposure to 

DDVP from food and that these 

uncertainties preclude EPA from 

departing from the 10X children’s safety 

factor. (Ref. 1 at 6). Specifically, NRDC 

cites to a list of uncertainties noted by 

EPA in a preliminary risk assessment for 

DDVP released in 2000. Those 

uncertainties involve the number of 

infants surveyed for the food 

consumption database; foods consumed 

from farm stands; use of data on residue 

decline from cooking studies; reliance 

on the residue sampling from the FDA 

Total Diet Study; and lack of monitoring 

data, and extensive use of data 

translation, for fumigated commodities. 

With the exception of the infant 

consumption issue, NRDC makes no 

claim other than to allege that ‘‘[e]ach of 

these shortcomings poses a serious risk 

of understating the risks posed by DDVP 

contamination of food.’’ (Id.). As to the 

infant consumption data, NRDC offers 

various challenges to the size and 

representativeness of the group of 

infants sampled in conjunction to the 

2000 preliminary risk assessment. 

NRDC acknowledges that EPA, in its 

response to the NRDC petition, states 

that it used updated infant consumption 

data but NRDC objects that ‘‘EPA does 

not assert that these data represent a 

statistically adequate or representative 

sample.’’ (Id.). Finally, NRDC implies 

that EPA thinks the data are not reliable 

by citing an EPA statement regarding 

the reliability of monitoring data. 

b. Background. NRDC made almost 

identical claims in its petition to revoke 

DDVP tolerances. EPA responded with a 

detailed examination of each of the 

factors cited by NRDC as well as several 

additional factors. (72 FR at 68684- 

68686). Where EPA identified 

weaknesses in the exposure database it 

either incorporated new, updated data 

in its risk assessment (for example, 

replacing data from the FDA Total Diet 

Study with data from USDA’s Pesticide 

Data Program) or explained how that 

weakness had been addressed by 

conservative assumptions. (72 FR at 

68684). This led to an entirely revised 

dietary exposure and risk assessment for 

DDVP. As to this revised assessment, 

EPA concluded that ‘‘its assessment of 

exposure to DDVP from food will not 

under-estimate but rather over-estimate, 

and in all likelihood substantially overestimate, DDVP exposure.’’ (72 FR at 

68686). EPA also noted that the largest 

‘‘driver’’ or contributor to dietary 

exposure of DDVP was DDVP in 

drinking water and not DDVP in food. 

(Id.). Specifically, as to food 

consumption data for infants, EPA 

stated that it had incorporated the most 

recent consumption data for infants that 

is used in all EPA pesticide risk 

assessments currently in its revised risk 

assessment for DDVP. This most recent 

data was collected at the direction of 

Congress in the FQPA. (Public Law 104- 

170, sec. 301; 110 Stat. 1489, 1511). 

c. Denial of hearing request. NRDC’s 

objection and request for a hearing on 

this sub-issue suffers from several 

infirmities. First, NRDC has objected to 

an outdated document, EPA’s 

preliminary risk assessment for DDVP. 

With the exception of the issue 

concerning food consumption data for 

infants, NRDC has made no effort to 

object to EPA’s current assessment of 

the reliability of various factors cited by 

NRDC in EPA’s petition response issued 

under FFDCA section 408(d)(4)(iii). 

When an objector does not challenge 

EPA conclusions in the section 

408(d)(4)(iii) order but rather challenges 

some prior conclusion that was 


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superseded by the section 408(d)(4)(iii) 

order, the objector has not raised a live 

controversy as to an issue material to 

the section 408(d)(4)(iii) order. (See 53 

FR 53176, 53191 (December 30, 1988) 

(where FDA responds to a comment in 

the final rule, repetition of the comment 

in objections does not present a live 

controversy unless the objector proffers 

some evidence calling FDA’s conclusion 

into question)). In fact, in these 

circumstances, it is questionable 

whether EPA has jurisdiction to 

consider the objection and hearing 

request because objections may only be 

filed as to a section 408(d)(4)(iii) order 

or other statutorily-specified action. (21 

U.S.C. 346a(g)(2)(A)). 

Second, NRDC has made no proffer of 

evidence supporting its claim that each 

of the factors cited from EPA’s 

preliminary risk assessment ‘‘poses a 

serious risk of understating the risks 

posed by DDVP contamination of food.’’

(Ref. 1 at 6). NRDC’s entire argument 

concerning the effect these factors (other 

than the infant food consumption data 

issue) would have on the DDVP 

exposure assessment is a single 

conclusory sentence. A hearing will not 

be granted on ‘‘mere allegations’’ or 

‘‘general contentions.’’ (40 CFR 

178.32(b)(2)). Although NRDC discusses 

the infant food consumption data issue 

at greater length, this discussion 

provides no support for granting a 

hearing. NRDC’s discussion is limited 

to: (1) a presentation of a short analysis 

of the adequacy of the superseded 

consumption data as opposed to the 

data upon which EPA relied in denying 

NRDC’s objection; and (2) a claim that 

EPA has not made a finding that the 

more recent infant food consumption 

data ‘‘represent a statistically adequate 

or representative sample.’’ (Ref. 1 at 6- 

7). However, the superseded data is 

irrelevant to the present proceeding and 

the allegation about an absent finding is 

framed as a procedural/legal challenge, 

not an identification of evidence 

supporting factual contentions. (See 53 

FR 53176, 53199 (December 30, 1998) 

(‘‘Rather than presenting evidence, [the 

objector] asserts that FDA did not 

adequately justify its conclusions. Such 

an assertion will not justify a hearing.’’). 

Third, ignoring for a moment the 

other serious flaws identified above, a 

hearing is inappropriate on this issue 

because NRDC has not shown a 

disputed factual issue. Rather, NRDC is 

essentially arguing about the correct 

conclusion that should be drawn from 

the factual findings made by EPA in its 

preliminary risk assessment. (47 FR 

55471, 55474 (December 10, 1982) 

(‘‘[Objectors] assertion about this 

evidence is, at best, an argument that a 

different inference (i.e., that the pieces 

are not ‘reasonably uniform’ and ‘cube 

shaped’) should be drawn from 

established fact (the dimensions of the 

pieces) than the agency has drawn. No 

hearing is required in such 

circumstances.’’). 

Finally, this entire issue suffers a 

materiality problem because dietary 

exposure to DDVP in food is so small 

relative to other DDVP exposures. As 

EPA noted in its petition denial, the 

‘‘latest dietary assessment shows that, 

by a large margin, the biggest driver in 

the DDVP dietary risk assessment are 

DDVP residues in water not food.’’ (72 

FR at 68686). Moreover, in evaluating 

aggregate exposure to DDVP from all 

sources EPA found that dietary 

exposure from food and water was 

‘‘insignificant’’ compared to exposures 

from pest strips. NRDC has made no 

showing that its concerns regarding 

dietary exposure to DDVP in food are 

material to the overall exposure 

assessment. (See 53 FR 53176, 53202 

(December 30, 1998) (The objector 

claims that radiation causes nutrient 

loss but ‘‘to justify a hearing on this 

point, it is not enough for [the objector] 

to simply assert that some nutrient loss 

can occur. [The objector] must present 

evidence that suggests that nutrient 

losses in food irradiated at doses 

permitted by the regulation are 

sufficiently large and would so affect 

the diet that such food would be 

nutritionally unwholesome or unsafe.’’). 

For all of the above reasons, NRDC’s 

hearing request on the adequacy of the 

DDVP dietary exposure assessment are 

denied. 

d. Denial of objections. EPA questions 

whether NRDC’s repetition of EPA’s 

statements from a preliminary risk 

assessment constitute an objection to a 

superseding risk assessment in a section 

408(d) petition denial. In any event, 

EPA has already explained in great 

detail in its petition denial why the 

factors cited in its preliminary risk 

assessment do not raise a concern that 

EPA in its latest assessment has 

understated DDVP dietary exposure. To 

the contrary, EPA concluded that its 

dietary assessment will ‘‘over-estimate, 

and in all likelihood substantially overestimate, DDVP exposure.’’ (72 FR at 

68686). Accordingly, NRDC’s objections, 

to the extent they merely repeat the 

claims in the petition, are denied for the 

same reasons stated in the petition 

denial. (72 FR at 68684-68686). 

EPA also denies NRDC’s apparent 

objection that the updated infant food 

consumption data is unreliable and thus 

EPA may not depart from the 10X 

children’s safety factor. The only two 

grounds NRDC cited for this objection 

were: (1) EPA’s alleged failure to 

confirm that these data are ‘‘statistically 

adequate or [a] representative sample;’’

and (2) a reference EPA made to 

monitoring data. NRDC’s arguments 

here are without merit. 

EPA has traditionally relied upon 

large scale surveys of food consumption 

conducted by the USDA in assessing 

dietary exposure and risk from 

pesticides. USDA generally conducts 

these surveys roughly every 10 years. 

EPA currently relies primarily on the 

Continuing Survey of Food Intakes by 

Individuals (‘‘CSFII’’) which was 

conducted in 1994-96. Prior surveys 

were performed by USDA in 1977-78 

and 1989-91. The 1994-96 CSFII was 

supplemented in 1998 to expand the 

number of data points for infants and 

children. As EPA has explained: ‘‘These 

surveys were designed to monitor food 

use and food consumption patterns in 

the U.S. population. The data were 

collected as a multistage, stratified, 

probability sample that was 

representative of the U.S. population. [] 

The most recent survey (CSFII 1994- 

1996/1998) was designed to obtain a 

sample that would provide equal 

precision over all sex-age domains. The 

data are used by a number of federal and 

state agencies to improve understanding 

of factors that affect food intake and the 

nutritional status of the U.S. population. 

[EPA’s Office of Pesticide Programs] 

considers the CSFII data adequate to 

model the daily variability in the U.S. 

diet.’’ (Ref. 5 at 39). 

The 1998 supplemental survey was 

collected in response to the mandate in 

the FQPA specifying that USDA, in 

consultation with EPA, was to 

‘‘coordinate the development and 

implementation of survey procedures to 

ensure that adequate data on food 

consumption patterns of infants and 

children are collected.’’ (Public Law 

104-170, sec. 301; 110 Stat. 1489, 1511). 

Congress specified that ‘‘[t]o the extent 

practicable, [these] procedures [] shall 

include the collection of data on food 

consumption patterns of a statistically 

valid sample of infants and children.’’

(Id.). Working together, EPA and USDA 

adopted a survey plan designed to be 

statistically reliable and representative. 

(Refs. 25 and 26). The 1998 survey 

involved sampling of 5,559 infants and 

children. When combined with the 

4,253 infants and children from the 

1994-96 survey, the total sample size for 

infants and children in the two surveys 

is near 10,000. EPA and USDA 

concluded that that ‘‘the sample sizes 

for each sex-age group [from the 

combined surveys] provide a sufficient 

level of precision to ensure statistical 

reliability of the estimates’’ except as to 


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certain low consumption items for 

individual age groups (e.g., infant 

consumption of lettuce). (Ref. 25 at 1). 

Comparison of the 1994-96 and 1998 

surveys indicated few statistical 

differences in nutrient consumption for 

the different age groups with the 

exception of 3-5 year olds. Even so, 

‘‘[t]he differences seen, although 

statistically significant, were relatively 

small and likely to be of little practical 

or biological significance.’’ (Ref. 26 at 2- 

3). 

Because EPA, in conjunction with 

USDA, has taken care to insure that its 

surveys of food consumption constitute 

a statistically valid and representative 

sample of infants and children, NRDC’s 

unsupported objection suggesting that 

this data is somehow inadequate is 

rejected. 

NRDC’s reference to an EPA statement 

about monitoring data does not in any 

way undermine this conclusion. EPA 

began a section of the petition denial 

which discusses, among other things, 

monitoring data of residues in food, 

infant food consumption data, and 

fumigant monitoring data, with the 

broad statement that ‘‘[i]n general, EPA 

disagrees that the monitoring data are 

unreliable.’’ (72 FR at 68684). While 

NRDC highlights the qualifying 

language ‘‘in general,’’ it ignores the 

critical following sentence that 

provides: ‘‘To the contrary, EPA 

believes that the monitoring data 

provide for an appropriately 

conservative risk assessment.’’ (Id.). The 

first sentence was qualified by the 

phrase ‘‘[i]n general,’’ because in two 

instances the EPA’s residue monitoring 

data were less than optimal; however, as 

noted in the second sentence, EPA 

concluded that the risk assessment was 

appropriately conservative because 

either the data in question were 

insignificant or other factors 

compensated for any uncertainty in the 

data. The first instance involved residue 

monitoring data for one minor 

commodity (berries not including 

strawberries) out of dozens of 

commodities where EPA relied on FDA 

enforcement monitoring data rather than 

its preferred source, data from USDA’s 

Pesticide Data Program. EPA prefers 

using the USDA data because it is 

collected using a sampling plan 

designed to capture a representative 

sample of food in the United States, 

whereas sampling for FDA enforcement 

data is targeted at food where violations 

are more likely to occur. Such targeted 

enforcement data generally overstates, 

in comparison to a more representative 

sample, both the frequency of finding 

pesticide residues in commodities and 

the level of the residues detected. In the 

second instance, fumigant monitoring 

data was not available for all bagged and 

packaged commodities so EPA 

translated data across commodities. 

Although noting that this translation 

introduced some uncertainty, EPA 

concluded that ‘‘this uncertainty was 

more than offset by other factors,’’

including a testing procedure that 

utilized maximum application rates and 

sampling within six hours of treatment 

and the assumption that all bagged and 

packaged commodities would be 

treated. Finally, the mention of 

‘‘monitoring data’’ is a reference to 

studies that ‘‘monitor’’ residues in food 

not surveys of people’s food 

consumption patterns. The latter topic 

was inadvertently included in a section 

of the order devoted to ‘‘[f]ood 

monitoring data.’’ (72 FR at 68683). 

Thus, the sentence cited by NRDC does 

not even refer to food consumption 

survey data. 

4. Pest strip exposure. NRDC claims 

that EPA’s assessment of exposure to 

DDVP from residential pest strips ‘‘is 

based on unsupported assumptions and 

inadequate data.’’ (Ref. 1 at 8). 

Accordingly, NRDC concludes the EPA 

lacks reliable data on DDVP exposure 

from pest strips and cannot reduce or 

remove the 10X children’s safety factor. 

EPA has identified seven separate 

allegations made by NRDC and they are 

analyzed individually below. 

a. Representativeness of Collins and 

DeVries study—i. Objection/hearing 

request sub-issue. NRDC argues that the 

Collins and DeVries study which EPA 

used to estimate DDVP exposure from 

pest strips had an inadequate sample 

size (15 houses). According to NRDC, 15 

houses is not adequate to represent the 

diversity of housing in the United States 

given the variations in housing design 

and ventilation characteristics. (Ref. 1 at 

7). Additionally, NRDC claims that, 

because the study was conducted in a 

single geographic area and for a period 

no longer than 91 days, it does not 

account for the varying weather 

conditions which can have differential 

effects on the movement and 

degradation of airborne residues. 

ii. Background. NRDC made the 

identical claim in its petition. EPA’s 

response in its petition denial order was 

two-fold. First, EPA pointed out that the 

Collins and DeVries study was not the 

only study considered by EPA in 

assessing DDVP exposure from pest 

strips. EPA reviewed several other 

studies involving over 100 homes in the 

United States and Europe. The results in 

the Collins and DeVries study were 

consistent with the results in the other 

studies and, thus, EPA concluded that it 

was reasonable to use the data from the 

Collins and DeVries study in assessing 

DDVP risk. (72 FR at 68692). Second, in 

response to this claim (as well as several 

of NRDC’s other claims), EPA 

substantially revised the DDVP 

exposure and risk assessment. (72 FR at 

68687-68691). Additional conservative 

assumptions were adopted and these 

conservative assumptions further offset 

any theoretical unrepresentativeness of 

the Collins and DeVries study. These 

assumptions were that exposed 

individuals spent 24 hours per day in a 

treated home, that a person spent all of 

the 24 hours per day in a room in the 

house with a pest strip, and that 

inclusion of a pest strip in a closet 

resulted in the same exposure as 

hanging the strip in the room itself. 

Further, EPA no longer averaged the 

exposure results from the houses in the 

study but evaluated each house 

individually. 

iii. Denial of hearing request. NRDC’s 

request for hearing on this issue is 

flawed for two reasons. First, as in its 

petition, NRDC proffers no evidence to 

support its claim that the Collins and 

DeVries study is inadequate due to the 

diversity of housing stock and 

geographic conditions in the United 

States. NRDC merely asserts that to be 

the case. However, hearings will not be 

granted on the basis of mere allegations 

or general contentions. (40 CFR 

178.32(b)(2); see also 68 FR 46403, 

46406-46407 (8/5/2003) (FDA denied a 

hearing involving a challenge to FDA’s 

reliance on consumption pattern data 

because the objector ‘‘did not present 

any specific information to dispute P & 

G’s consumption pattern data; instead, 

[objector] simply asserted that other 

consumption patterns were likely.’’); 

accord Community Nutrition Institute v. 

Novitch, 773 F.2d 1356, 1363 (D.C. Cir. 

1985) (‘‘Mere differences in the weight 

or credence given to particular scientific 

studies . . . are insufficient [to show a 

material issue of fact for a hearing].’’)). 

Second, NRDC’s hearing request is 

inadequate because NRDC does not 

object to the basis EPA asserted in its 

petition denial for concluding that the 

Collins and DeVries study does provide 

a sufficient basis for estimating 

residential exposure. Specifically, 

NRDC does not challenge EPA’s 

conclusion that the Collins and DeVries 

study is consistent with several other 

pest strip studies and proffer evidence 

in support of that challenge. Neither 

does NRDC challenge and proffer 

evidence regarding EPA’s conservative 

use of the Collins and DeVries study in 

assessing exposure. Rather, NRDC just 

repeats its assertions regarding the 

unrepresentativeness of the Collins and 

DeVries study from its petition. This 


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failure to challenge the basis of EPA’s 

petition denial affects the materiality of 

the objection and hearing request. Even 

if NRDC could demonstrate in a hearing 

that the ventilation design of a house, 

for example, can affect the rate at which 

airborne contaminants are dissipated, 

that evidence would not contradict the 

fact that the Collins and DeVries study 

is consistent with DDVP pest strip 

studies in over 100 other homes in 

varying locations. 

Prior FDA decisions under its 

regulations are instructive here. 

Objections and hearing requests were 

filed in response to a food additive 

regulation covering the irradiation of 

poultry. (62 FR 64102 (December 3, 

1997). The objector argued that the 

addition of an anti-oxidant (ethoxyquin) 

to irradiated chicken prior to the 

chicken’s use in animal feeding studies 

compromised the studies because the 

ethoxyquin would have decreased the 

level of lipid peroxides in the chicken 

to levels found in chicken that had not 

been irradiated. The FDA noted, 

however, that it had considered the 

question of ethoxyquin’s effect on lipid 

peroxide levels in the final rule and 

determined that while ethoxyquin can 

retard the normal oxidation of chicken 

fat to peroxides, ethoxyquin cannot 

reverse oxidation that has already 

occurred. FDA denied the hearing 

request reasoning that because the 

objector did ‘‘not dispute FDA’s 

explanation in the final rule as to why 

addition of ethoxyquin did not 

compromise the CIVO studies, and 

provided no information that would 

have altered the agency’s conclusion on 

this issue . . . there is no factual issue 

that can be resolved by available and 

specifically identified reliable 

evidence.’’ (62 FR at 64105; see also 53 

FR 53176, 53191 (December 30, 1988) 

(FDA denied a hearing request noting 

that given FDA’s prior conclusion that 

the studies relied upon by the objector 

were unreliable, the ‘‘burden shifted to 

[the objector] to maintain the viability of 

its objection by proffering some 

information that called into question the 

agency’s conclusion on this matter.’’)). 

Similarly, here, NRDC has not 

challenged the basis EPA asserted for 

rejecting NRDC’s challenge to EPA’s 

reliance on the Collins and DeVries 

study and NRDC has not proffered any 

information calling into question EPA’s 

conclusion. 

iv. Denial of objection. Because NRDC 

offers no basis for its objection to EPA’s 

denial of the challenge in its petition to 

EPA’s reliance on the Collins and 

DeVries study—other than the claims 

made in its petition, itself—EPA denies 

the objections for the reasons in the 

petition denial order (i.e., the 

consistency of the Collins and DeVries 

study with other DDVP pest strip 

studies and the conservativeness of the 

DDVP pest strip exposure assessment). 

b. Sampling location in the Collins 

and DeVries study—i. Objection/hearing 

request sub-issue. NRDC argues that the 

Collins and DeVries study is flawed 

because air concentration levels of 

DDVP were sampled in only one 

location in the house. According to 

NRDC, this sampling regime was 

inadequate because it ‘‘provides no 

information about the movement of 

residues from room-to-room and 

therefore exposure in other rooms in the 

homes.’’ (Ref. 1 at 7). 

ii. Background. NRDC repeats this 

claim verbatim from its petition. The 

petition denial order rejected this 

challenge to the Collins and DeVries 

study and the manner of EPA’s use of 

the study in its exposure assessment 

noting that ‘‘the sample location in each 

instance was in a room with a pest strip, 

pest strips were used in other rooms of 

the house, and EPA assumed, for its 

calculation of the MOE, that the air 

concentration for all areas of a house is 

the same as at the sampled location.’’

(72 FR at 68692). 

iii. Denial of hearing request. This 

objection and hearing request does not 

involve a genuine and substantial issue 

of disputed fact. There is no dispute 

concerning how or where sampling was 

done in the Collins and DeVries study 

or how EPA used that data in estimating 

DDVP exposure from pest strips. 

NRDC’s objection attacks EPA’s 

conclusion that it is reasonable to assess 

residential DDVP exposure from pest 

strips using air concentrations of DDVP 

from rooms which contained a pest 

strip. A challenge to an EPA inference 

drawn from undisputed facts does not 

qualify as a disputed factual question. 

(47 FR 55471, 55474 (December 10, 

1982) (‘‘[Objectors] assertion about this 

evidence is, at best, an argument that a 

different inference (i.e., that the pieces 

are not ‘reasonably uniform’ and ‘cube 

shaped’) should be drawn from 

established fact (the dimensions of the 

pieces) than the agency has drawn. No 

hearing is required in such 

circumstances.’’)). Moreover, NRDC 

does not explain why knowledge of the 

amount of room-to-room DDVP 

movement is relevant given that EPA 

based its exposure assumption on the 

level of DDVP found in a room with a 

pest strip, much less proffer any 

evidence to suggest why this issue is 

material and should be resolved in its 

favor. For all of these reasons, NRDC’s 

hearing request on this issue is denied. 

iv. Denial of objection. This objection 

is denied for the same reason stated in 

the petition denial order: knowledge of 

the amount of room-to-room movement 

of DDVP is irrelevant if EPA bases its 

exposure assessment on a room that 

contains a pest strip. In both its petition 

and its objections, NRDC cites the 

following statement from EPA’s 

preliminary risk assessment as 

supporting its conclusion regarding the 

inadequacy of use of a single air monitor 

in the Collins and DeVries study: ‘‘A 

more accurate exposure would be 

possible if air measurements were 

available from different rooms in the 

house.’’ (Ref. 1 at 7). NRDC, however, 

misunderstands the thrust of this 

sentence. EPA was simply pointing out 

that monitoring in rooms without pest 

strips would have provided a more 

accurate and realistic - i.e., lower - 

estimate of exposure than using values 

from a room containing a pest strip. The 

sentences immediately following the 

language quoted by NRDC make this 

clear. EPA stated: ‘‘Limited data suggest 

that the level of Dichlorvos in the air 

declines with distance from the resin 

pest strip. There are data from the 

Dichlorvos Flea Collar Study that show 

Dichlorvos levels are lower some 

distance away from the pet flea collar.’’

(Ref. 27 at 53). 

c. Averaging DDVP concentrations 

over 120 days—i. Objection/hearing 

request sub-issue. NRDC objects to 

EPA’s assessment of exposure to pest 

strips challenging EPA’s alleged use of 

a 120–day average of DDVP 

concentration levels. NRDC argues that 

‘‘[r]ather than using averages, the 

Agency should have presented the range 

of risks displayed over time, peak 

measurements, and the daily monitoring 

data so that trends over time could be 

determined.’’ (Ref. 1 at 7). 

ii. Background. NRDC repeats this 

claim verbatim from its petition. In its 

petition denial order, EPA agreed with 

NRDC and revised its residential 

exposure assessment to examine 

exposure and risk based on the first day 

of exposure after hanging the pest strip, 

the first 2 weeks of exposure, and 

exposure over a 91 day period. (72 FR 

at 68687). 

iii. Denial of hearing A hearing can 

only be based on a genuine issue of 

disputed fact. Where a party’s factual 

allegations are contradicted by the 

record, there is no genuine dispute. (57 

FR 6667, 6672 (February 27, 1992) (‘‘A 

hearing must be based on reliable 

evidence, not on mere allegations or on 

information that is inaccurate and 

contradicted by the record.’’). 

iv. Denial of objection. NRDC’s 

objection is directed at a prior, 


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superseded risk assessment, not the risk 

assessment relied upon in the petition 

denial order. Thus, this objection is not 

material to this proceeding and is 

denied. (See Unit VIII.D.3.c.). 

d. Replacement cycle for pest strips—

i. Objection/hearing request sub-issue. 

NRDC objects to EPA’s assumption that 

pest strips are replaced no more 

frequently than 120 days even though 

the pest strip label does not prohibit 

more frequent replacement. (Ref.1 at 8). 

NRDC argues that EPA has no data to 

substantiate this assumption and claims 

that homeowners may decide ‘‘to 

replace strips sooner ‘for good 

measure.’’’ (Id.). Recognizing that EPA 

decreased its assumption concerning the 

replacement cycle to 91 days in the 

revised risk assessment in the petition 

denial order, NRDC asserts that this 

value is equally arbitrary. 

ii. Background. The challenge to the 

120–day replacement assumption was 

included in NRDC’s petition. EPA 

responded to NRDC’s argument in the 

petition denial order by decreasing its 

assumption as on the replacement cycle 

of pest strips to 91 days. (72 FR at 

68692). 

iii. Denial of hearing. This sub-issue 

does not meet the standard for a 

hearing. NRDC disputes the 

reasonableness of EPA’s choice of a 

replacement cycle for pest strips in the 

absence of a restriction on the pesticide 

label or data documenting consumer 

usage. NRDC proffers no evidence 

challenging EPA’s use of a 91–day 

replacement cycle. Rather, NRDC asserts 

a legal argument that in the absence of 

specific data on consumer usage, EPA 

may not make an assumption about 

consumer practices. Hearings are not 

appropriate on legal questions. (40 CFR 

178.32(b)(1)). Similarly, NRDC’s 

speculation about how often 

homeowners may replace pest strips 

does not constitute an evidentiary 

proffer justifying a hearing. (See 57 FR 

33244, 33248 (July 27, 1992) (NRDC 

claimed that the removal of premix 

batch analysis would lead to 

misformulation of selenium in feeds. A 

hearing was denied because NRDC 

‘‘provided no factual information to 

support its claim . . . . [A] hearing will 

not be granted on the basis of mere 

allegations.’’)). 

iv. Denial of objection. In its 

preliminary risk assessment and in the 

IRED, EPA assumed that pest strips 

would be replaced no more frequently 

than 120 days because the pest strip 

label specifies: ‘‘Drafts, weather, and 

other conditions may affect the 

performance, but treatment usually last 

for 4 months. Record the date of 

installation and replace with a new, 

fresh, full-strength strip at the end of 4 

months or when effectiveness 

diminishes.’’ (Ref. 28). Given that the 

manufacturer was essentially 

designating 120 days as the likely 

effective period and that consumers 

might leave the pest strips up for either 

longer or shorter periods, EPA assumed 

that 120 days was a reasonable estimate 

of the average replacement cycle for pest 

strips. EPA generally uses average 

values for chronic exposure scenarios 

because over time high and low values 

tend to average out. (Ref. 5 at 42). 

Nonetheless, in recognition of NRDC’s 

contention that homeowners might 

replace strips more frequently, EPA 

amended its pest strip exposure to 

assume a 91–day replacement cycle (the 

length of the Collins and DeVries study) 

rather than extrapolate the data from the 

Collins and DeVries study over 120 days 

as was done previously. EPA believes 91 

days is a reasonable estimate of the 

replacement cycle especially given the 

label language and the numerous 

conservative assumptions in the risk 

assessment such as, for example, the 

assumption of 24 hours per day 

exposure in a room containing a pest 

strip. Accordingly, NRDC’s objection on 

this sub-issue is denied. 

e. Number of pest strips—i. Objection/ 

hearing request sub-issue. NRDC claims 

that EPA’s assessment of DDVP 

exposure from pest strips is not based 

on adequate data because EPA does not 

have any data on how many strips 

people use in their homes. EPA assessed 

residential DDVP exposure based on the 

Collins and DeVries study which used 

3-4 strips per house in each of the 

studied houses. NRDC argues that some 

homeowners may use more than 3-4 

strips because there is no limitation on 

the label as to the number of strips per 

house. 

ii. Background. NRDC repeats this 

claim verbatim from its petition. EPA 

rejected NRDC’s concern in the petition 

denial order reasoning that its 

assessment was based on data on the air 

concentration of DDVP in a room 

containing a pest strip. (72 FR at 68692). 

EPA also noted that the only strips 

allowed in occupied areas of the home 

under the current registration are for 

closets, wardrobes, or cupboards and 

given that they treat a relatively small 

space, compared to the bigger strips 

used in the Collins and DeVries study, 

they are unlikely to result in significant 

DDVP air concentrations in rooms other 

than in the room containing the treated 

area. (Id.). 

iii. Denial of hearing. NRDC has not 

alleged and proffered evidence on a 

genuine and substantial issue of 

disputed fact. NRDC speculates that use 

of pest strips in every, or almost every, 

room in a house may lead to higher 

residues in a room containing a pest 

strip than a room containing a pest strip 

in a house which has a pest strip in 3- 

4 rooms. Based on this speculation, 

NRDC claims that EPA’s exposure 

assessment is inadequate because EPA 

has not documented how many strips 

people use in their houses. A hearing 

will not be granted on the basis of mere 

allegations or speculation about what 

other studies might show. (See 57 FR 

33244, 33248 (July 27, 1992) (NRDC 

claimed that the removal of premix 

batch analysis would lead to 

misformulation of selenimum in feeds. 

A hearing was denied because NRDC 

‘‘provided no factual information to 

support its claim . . . . [A] hearing will 

not be granted on the basis of mere 

allegations.’’)). 

iv. Denial of objection. For several 

reasons, NRDC’s speculation that a 

house containing strips in nearly every 

room might lead to greater DDVP 

exposures than estimated by EPA must 

be rejected. First, EPA based its DDVP 

pest strip exposure assessment on a 

study (Collins and DeVries) which 

measured DDVP concentrations in a 

room containing a pest strip. Second, 

the Collins and DeVries study did not 

involve a house with a single strip but 

used pest strips in 3-4 rooms of the 

studied houses. Third, the results of the 

Collins and DeVries study were 

consistent with the results of several 

other pest strip studies. Fourth, 

although corrected for the smaller size 

of current pest strips compared to the 

pest strips used in the Collins and 

DeVries study, EPA did not adjust its 

assessment for the fact that current 

strips may not be used for general space 

treatment but must be put in closets, 

wardrobes, or cupboards. Taking into 

account these factors, EPA’s assessment 

of exposure from DDVP pest strips was 

reasonable and based upon adequate, 

reliable data to reduce or remove the 

children’s safety factor. 

f. Exposure time per day—i. 

Objection/hearing request sub-issue. 

NRDC objects that it was unreasonable 

for EPA to assume that the high end 

exposure period in the home is 16 hours 

and that a low end exposure period is 

2 hours. NRDC argues that some groups 

of people may spend significantly 

greater amounts of time in their homes. 

NRDC asserts that EPA does not 

adequately justify these assumptions in 

its petition denial order. 

ii. Background. NRDC repeats this 

claim verbatim from its petition. In 

response to NRDC’s petition, EPA 

substantially revised its pest strip 

exposure assessment. As to exposure 


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periods, EPA completely dropped its 

prior approach and assessed exposure 

assuming a person spent 24 hours per 

day in their home in a room containing 

a pest strip. (72 FR at 68687). 

iii. Denial of hearing. A hearing can 

only be based on a genuine issue of 

disputed fact. Where a party’s factual 

allegations are contradicted by the 

record, there is no genuine dispute. (57 

FR 6667, 6672 (February 27, 1992) (‘‘A 

hearing must be based on reliable 

evidence, not on mere allegations or on 

information that is inaccurate and 

contradicted by the record.’’). 

iv. Denial of objection. NRDC’s 

objection is directed at a prior, 

superseded risk assessment, not the risk 

assessment relied upon in the petition 

denial order. Thus, this objection is not 

material to this proceeding and is 

denied. (See Unit VIII.D.3.c.). 

g. Movement of DDVP from 

unoccupied areas of the home to 

occupied areas—i. Objection/hearing 

request sub-issue. NRDC claims that 

EPA does not have a sufficient basis for 

its conclusion that pest strips used in 

unoccupied places in a house (garages, 

attics, crawl spaces, sheds) will not 

migrate to occupied portions of the 

house. Thus, NRDC argues EPA does not 

have reliable data to reduce or remove 

the children’s safety factor. 

ii. Background. NRDC made the same 

argument in its petition. Additionally, 

in the petition, NRDC cited a study with 

another pesticide which NRDC claimed 

showed that pesticides could migrate 

into the house. EPA disagreed with 

NRDC’s assertion, pointing out that 

migration was unlikely unless the 

unoccupied portion was connected to 

the air exchange system for the house. 

EPA also explained in detail why the 

study cited by NRDC was not relevant 

to DDVP. NRDC did not renew its 

arguments based on this study. 

iii. Denial of hearing. NRDC has not 

alleged and proffered evidence on a 

genuine and substantial issue of 

disputed fact. NRDC speculates that use 

of pest strips in unoccupied areas of a 

house may lead to migration of DDVP 

residues to occupied portions of the 

house. Based on this speculation, NRDC 

claims that EPA’s exposure assessment 

is inadequate because EPA has not 

documented that such migration does 

not occur. A hearing will not be granted 

on the basis of mere allegations or 

speculation about what other studies 

might show. (See 57 FR 33244, 33248 

(July 27, 1992) (NRDC claimed that the 

removal of premix batch analysis would 

lead to misformulation of selenium in 

feeds. A hearing was denied because 

NRDC ‘‘provided no factual information 

to support its claim . . . . [A] hearing will 

not be granted on the basis of mere 

allegations.’’)). 

iv. Denial of objection. NRDC’s 

objection is denied. Given EPA’s 

knowledge of the chemical properties of 

DDVP, it was reasonable to assume that 

DDVP would not migrate from 

unoccupied portions of the home to 

occupied portions absent some type of 

air exchange connection between the 

two areas. DDVP is a highly volatile 

chemical that quickly degrades once 

released to the environment. EPA 

reasonably concluded that the low 

concentration of airborne DDVP 

produced from a DDVP pest strip would 

not penetrate the walls of a home in 

meaningful amounts. 

E. Response to Specific Issues Raised in 

Objections and Hearing Requests - 

Reliance on Human Study 

1. Background. In making its FFDCA 

tolerance reassessment decision and 

FIFRA reregistration decision for DDVP, 

EPA relied upon one human toxicity 

study in deriving an acceptable level of 

exposure for several exposure scenarios. 

The study in question was conducted in 

1997 by A.J. Gledhill. In this study, six 

male volunteers were administered 7 mg 

of DDVP in corn oil (equivalent to 

approximately 0.1 mg/kg/day) via 

capsule daily for 21 days. Three control 

subjects received corn oil as a placebo. 

Baseline values for RBC cholinesterase 

activity for each study participant were 

determined based upon repeated 

measurements prior to the 

administration of DDVP. After dosing 

started, RBC cholinesterase activity was 

monitored on days 2, 4, 7, 9, 11, 14, 16, 

and 18, and then on day 25 or 28 postdosing. Although no toxicity 

attributable to administration of DDVP 

was reported by the test subjects, mean 

RBC cholinesterase activity was 

statistically significantly reduced in 

treated subjects on days 7, 11, 14, 16, 

and 18. These values were 8, 10, 14, 14, 

and 16 percent below the pre-dose 

mean. (Refs. 15 and 16). 

EPA’s decision to rely on the Gledhill 

study was made pursuant to its Human 

Research rule. As explained in Unit 

III.D, that rule establishes different 

ethical standards for the review of 

completed human studies depending on 

whether they were initiated before or 

after the effective date of the rule on 

April 7, 2006. For an intentional human 

exposure study such as the Gledhill 

study, that was initiated prior to April 

7, 2006, EPA is barred, subject to a very 

limited exception, from relying on it if 

there is clear and convincing evidence 

that the conduct of the research was 

fundamentally unethical or significantly 

deficient with respect to the ethical 

standards prevailing at the time the 

research was conducted. (40 CFR 

26.1704, 1706). Further, the rule limits 

the human research that can be relied 

upon by EPA to ‘‘scientifically valid and 

relevant data.’’ (40 CFR 26.1701). 

Finally, because the Gledhill study was 

conducted with the purpose of 

identifying or measuring a toxic effect, 

EPA is required by the rule to submit its 

determination regarding these issues to 

an independent expert advisory body 

known as the Human Studies Review 

Board (‘‘HSRB’’) for review. These 

procedures were followed with regard to 

the Gledhill study. 

Previously, NRDC has challenged the 

lawfulness of the Human Research rule. 

Following promulgation of the Human 

Research Rule, NRDC filed a petition for 

judicial review of the rule in the United 

States Court of Appeals for the Second 

Circuit. (NRDC v. U.S. EPA, No. 06- 

0820-ag (2d Cir.)). That case has been 

briefed and argued and is awaiting 

decision. 

NRDC also previously challenged the 

scientific merit and ethics of the 

Gledhill study in comments to EPA and 

to the HSRB. Specifically as to the 

HSRB, NRDC filed written comments 

prior to the HSRB’s review of EPA’s 

determination regarding the 

appropriateness of relying on the 

Gledhill study and also presented oral 

testimony at the public hearing the 

HSRB held with regard to that study. 

Subsequently, the HSRB, after taking 

into account the comments of NRDC 

and others, advised EPA that reliance on 

the Gledhill study was consistent with 

the Human Research rule. EPA relied 

heavily on the analysis of the HSRB in 

denying NRDC’s petition to revoke 

DDVP tolerances. (72 FR at 68675). 

In its petition to revoke DDVP 

tolerances, NRDC repeated its 

arguments made to the HSRB as to why 

the Gledhill study does not comply with 

the Human Research rule. As support, 

NRDC cited to a draft HSRB report on 

the Gledhill study, released shortly 

before NRDC filed its petition, which 

noted scientific and ethical deficiencies 

in the study. (Ref. 2 at 26). NRDC did 

not acknowledge, however, that despite 

identifying deficiencies in the Gledhill 

study, the HSRB, in its draft report, 

stated its agreement with EPA’s 

determination that it would be 

acceptable to rely on the Gledhill study. 

In its objections, NRDC once again 

makes the same arguments on the 

Gledhill study it made to the HSRB and 

in its petition to EPA (including the 

misleading reference to a portion of the 

draft report of the HSRB). Similar to the 

approach taken in the petition, NRDC 

does not even acknowledge the 


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recommendations made by the HSRB in 

its draft and final decisions despite 

EPA’s explicit reliance on the HSRB’s 

reasoning in EPA’s petition denial 

order. 

NRDC’s objections also include a 

challenge to the legality of the Human 

Research rule paralleling the case 

pending in the Second Circuit. 

2. Challenge to the human research 

rule—a. Objection/hearing request subissue. NRDC argues that ‘‘to the extent 

[its] facial challenge to the [Human 

Research] rule is not proper,’’ it is 

renewing its arguments regarding the 

legality of the rule in its objections. (Ref. 

1 at 9-10). The objections incorporate by 

reference NRDC’s legal briefs filed in the 

Second Circuit and its comments filed 

on the Human Research rule as support 

for this objection. In its legal briefs, 

NRDC argues that EPA’s rule is 

inconsistent with a congressional 

funding moratorium in an 

Appropriations Act. (Ref. 29). That Act 

prohibited EPA from ‘‘accept[ing], 

consider[ing] or rely[ing] on third-party 

intentional dosing human toxicity 

studies for pesticides . . . until [EPA] 

issues a final rulemaking on this 

subject.’’ (Public Law 109-54, sec. 201, 

119 Stat. 499, 531 (August 2, 2005)). 

According to NRDC, EPA did not 

comply with this legislation’s 

requirement that the EPA human testing 

rule bar testing on pregnant women, 

infants and children and be consistent 

with the principles in a 2004 National 

Academy of Sciences Report and the 

Nuremburg Code on human 

experimentation. (Ref. 29 at 23). NRDC 

did not specifically lay out the 

arguments in its legal briefs in its 

objections other than to include a 

summary of some of the principles of 

the Nuremberg Code. (Ref. 1 at 11-12). 

Similar arguments are made in NRDC’s 

comments on EPA’s proposed Human 

Research rule. (Ref. 30). 

b. Background. Arguments concerning 

the legality of the Human Research Rule 

were not contained in the petition. 

c. Denial of hearing request. In this 

sub-issue, NRDC presents, by reference, 

various arguments that the Human 

Research rule is not consistent with 

congressional legislation bearing on the 

rule. These arguments raise questions 

regarding the proper interpretation of 

statutory language and hearings are not 

appropriate on such issues. (40 CFR 

178.32(b)(1)). 

d. Denial of objection. To the extent 

this matter is not resolved by the 

Second Circuit and NRDC has standing 

to challenge a rule whose ‘‘primary 

concern’’ is the ‘‘[p]rotection of the 

health and safety of human test 

subjects,’’ (Ref. 1 at 15), EPA denies 

NRDC’s objections to the legality of the 

Human Research rule. EPA believes the 

Human Research rule is fully consistent 

with the Appropriations Act and EPA 

has fully explained the basis for this 

conclusion in the rulemaking record 

(EPA–HQ–OPP–2003–0132) and its 

legal brief filed in the Second Circuit 

proceeding. (Ref. 31). 

3. Challenge to reliance on the 

Gledhill Study—a. Statistical power - 

too few subjects to detect an effect—i. 

Objection/hearing request sub-issue. 

NRDC objects that the number of test 

subjects in the Gledhill study was low 

and thus there are statistical issues with 

extrapolating from the results of the 

Gledhill study to the general human 

population. (Ref. 1 at 13). In part, NRDC 

frames this argument as the Gledhill 

study lacks ‘‘statistical power’’ and 

NRDC references four published letters 

or articles in support of this claim. (Ref. 

1 at 15). Further, NRDC claims that the 

statistical power issue is particularly 

important for studies such as the 

Gledhill study which measure 

cholinesterase inhibition because of the 

variability among individuals of 

cholinesterase inhibition over time. 

According to NRDC, the ‘‘range of 

variability both between and for the 

individual test subjects means that even 

greater than the customary number of 

test subjects would be required to 

permit adequate statistical power to 

detect effects caused by the test 

substance above background 

variations.’’ (Ref. 1 at 13). As evidence 

of this cholinesterase inhibition 

variability in humans, NRDC cites to 

another human study by Gledhill (MRID 

# 4428802 rather than MRID # 

44248801). 

NRDC’s objection here appears to be 

confusing two separate issues: (1) did 

the Gledhill study have sufficient 

statistical power to detect an effect 

caused by DDVP; and (2) does the 

Gledhill study contain sufficient data to 

reliably estimate a safe dose for humans. 

The first issue is addressed in this Unit 

and the second in Unit VIII.E.3.b. 

ii. Background. NRDC’s objection 

repeats assertions made in its petition to 

revoke DDVP tolerances and its 

comments on the DDVP IRED. (Ref. 2 at 

26-27; Ref. 23 at 14-17). EPA rejected 

NRDC’s claims about statistical power, 

explaining that ‘‘[a]lthough as a general 

matter more subjects would provide 

greater ‘statistical power,’ in this case 

the use of 6 to 9 subjects with the 

appropriate statistical methodology is 

acceptable to EPA because a positive 

response was seen.’’ (72 FR at 68675). 

EPA also noted that the variability 

within the cholinesterase inhibition of 

the tested subjects ‘‘is not large, 

particularly since the percentage 

inhibition in all instances was at the 

marginal end of the range.’’ (Id.). 

iii. Denial of hearing. A hearing is not 

required on NRDC’s statistical power 

claim because the concept of statistical 

power is simply not applicable to the 

conclusions EPA drew with regard to 

the Gledhill study and thus this issue is 

not material to NRDC’s requested relief. 

Further, the evidence proffered by 

NRDC would not, if established, resolve 

this issue in NRDC’s favor. 

To understand EPA’s ruling here, 

some basic definitional information on 

the concept of ‘‘statistical power’’ and 

how it applies in the context of toxicity 

studies may be helpful. Toxicity testing 

is designed to test the veracity of the 

hypothesis that there will be no 

differences in health outcomes between 

treated and untreated (control) subjects. 

Statisticians refer to this hypothesis as 

the ‘‘null hypothesis.’’ The ‘‘alternative 

hypothesis’’ is that there will be a 

difference between treated and control 

subjects. In general terms, statistical 

power measures the probability that a 

toxicological study will find a 

treatment-related adverse health 

outcome when there is a treatmentrelated adverse effect to be found. (Ref. 

32 at 125 and n.144). In the language of 

a statistician, statistical power measures 

the ‘‘probability of rejecting the null 

hypothesis when the alternative 

hypothesis is right.’’ (Id.). A study with 

a statistical power value of near one (1) 

would have a very high chance of 

(properly) rejecting the null hypothesis 

if the alternative hypothesis is true, 

whereas a power value close to zero (0) 

would indicate that there is little chance 

that the study will identify any true 

adverse health outcomes occurring as a 

result of treatment. 

Statistical power can also be used to 

calculate the probability that the study 

will falsely find that there is no 

difference in the health outcomes 

between treated and control subjects, 

that is, whether the study will falsely 

affirm the null hypothesis. The 

probability of such a false negative, is 

determined by subtracting the statistical 

power of a study from one (1). (Id.). 

Thus, the chance that a study will result 

in a false negative is directly related to 

the chance that the study will identify 

any effects present. For example, if a 

study has low statistical power, there 

will be a low probability that the study 

will find an effect if there is one and a 

high probability that the study will 

falsely affirm that there is no effect. 

Statistical power, therefore, is a 

important tool in designing studies to 

ensure that effects from treatment are 

not missed and may play a role in 


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evaluating completed studies that 

confirm the null hypothesis to 

determine the probability that the null 

hypothesis was not falsely affirmed (i.e., 

a false negative). 

If analysis of a toxicological study 

shows that there are treatment-related 

effects (i.e., the null hypothesis of no 

treatment-related effect is rejected), then 

the question of the statistical power of 

the study becomes largely irrelevant. 

Put another way, if a study shows a 

positive outcome, the probability that 

the study might have produced a false 

negative becomes a moot point. 

Importantly, with the Gledhill study, 

the null hypothesis of no treatmentrelated effect was rejected: that is, the 

HSRB and EPA concluded that there 

was a significant difference in 

cholinesterase inhibition both between 

controls and DDVP-treated subjects and 

between the inhibition levels pre- and 

post-treatment of the DDVP-treated 

subjects. 

With that background, the scientific 

papers cited by NRDC can be more 

easily followed. First, NRDC cites a onepage letter to the Environmental Health 

Perspectives journal which was coauthored by Jennifer Sass, a NRDC 

senior scientist, and a subsequent letter, 

again co-authored by Sass, that 

responded to various letters expressing 

a different viewpoint. (Ref. 1 at 15, and 

Refs. 33 and 34). The topic of both Sass 

letters is nicely captured by the title 

attached to the first letter: ‘‘Industry 

Testing of Toxic Pesticide on Human 

Subjects Concluded ‘No Effect,’ Despite 

the Evidence.’’ (Ref. 33 ). 

The first letter discusses the DDVP 

Gledhill study and a second human 

study involving a different pesticide. 

With regard to the DDVP Gledhill study, 

Sass criticizes Amvac’s analysis of that 

study. Amvac had concluded that the 

Gledhill study demonstrated a NOAEL 

arguing that the cholinesterase 

inhibition effects seen at the single dose 

in that study were not biologically 

significant. Sass counters that ‘‘the only 

biological end point measured in the 

study was cholinesterase inhibition, and 

this was significantly inhibited.’’ (Ref. 

33 at A150). As to statistical power, Sass 

claims that studies involving only a few 

human subjects ‘‘often lack enough 

subjects to provide adequate statistical 

power to detect an effect if it is 

present.’’ (Id.). 

The second letter repeats this latter 

assertion and claims that the statistical 

power of human studies then available 

have such low statistical power that 

they ‘‘practically guarantee[d] a finding 

of no effect.’’ (Ref. 34 at A340). Sass 

then returns to the Gledhill study and 

notes with approval EPA’s conclusion 

that that study demonstrated a LOAEL: 

‘‘the U.S. Environmental Protection 

Agency (EPA) rejected AMVAC’s 

interpretation of the results, instead 

concluding that ‘the reduction in RBC 

cholinesterase activity was considered 

by the Hazard ID [identification] 

Committee to be biologically significant, 

and the dose tested was considered to 

be a lowest observed effect level 

(LOEL).’’’ (Id.). EPA’s reversal of the 

Amvac conclusion is cited by the letter 

as illustrative of bias by chemical 

manufacturers in the design and 

interpretation of studies. 

For at least two reasons, these letters 

neither demonstrate the materiality of 

NRDC’s statistical power claims nor 

constitute a sufficient evidentiary 

proffer. First, although they do contain 

allegations about low statistical power 

of human studies with low numbers of 

subjects, they only address the question 

of whether such studies can detect an 

effect even if an effect is present (i.e., 

are they likely to falsely affirm the null 

hypothesis that there are no treatmentrelated adverse effects). In the DDVP 

Gledhill study, however, EPA and the 

HSRB concluded that the study did 

identify an adverse effect. Accordingly, 

the letters have little relevance to EPA’s 

ultimate finding with regard to the 

Gledhill study. Second, these letters do 

not challenge EPA’s analysis of the 

Gledhill study - rather, they ratify it. 

Thus, the letters do not proffer 

evidence, which would, if established, 

resolve a material issue in NRDC’s favor. 

(See 57 FR 33244, 33246 (July 7, 1992) 

(Studies cited by NRDC do not provide 

a basis for the hearing because they 

‘‘support the [FDA] conclusion in 

question.’’)). 

NRDC also cites two articles by Alan 

Lockwood. One is an article in the 

American Journal of Public Health 

discussing ethical and scientific 

considerations with regard to six human 

toxicology studies, including the 

Gledhill study at issue in this 

proceeding. (Refs. 1 at 15; and 35). The 

second is a one-page summary of the 

earlier article that was published in The 

Environmental Forum. (Ref. 36). The 

first article contains the following 

paragraph discussing statistical power: 

A power analysis to define the proper size 

of study group(s) is an essential part of the 

design. If too many participants are enrolled, 

the excess will be subjected to unnecessary 

risk. If too few are enrolled, the investigator 

risks erroneous acceptance of the null 

hypothesis. Underpowered studies are 

inconclusive, and all participants in an 

underpowered study will have been exposed 

to risk unnecessarily. All of these studies 

were underpowered. 

(Ref. 35 at 1912). There is little to no 

explanation provided in the article for 

the ‘‘underpowered’’ conclusion other 

than the notation that the six studies 

involved young healthy adults. There is 

little, if any, discussion of the Gledhill 

DDVP study at issue in this proceeding. 

The summary article adds nothing new 

to the longer article. 

Like the Sass letters, therefore, the 

Lockwood articles do not constitute a 

proffer of evidence that if established 

would resolve a material issue in favor 

of NRDC. Not only do they not proffer 

any evidence, they focus on an issue not 

involved here - do human studies, such 

as the Gledhill study, have sufficient 

statistical power to avoid ‘‘erroneous 

acceptance of the null hypothesis.’’ Both 

EPA and the HSRB rejected the null 

hypothesis as to the Gledhill study (i.e., 

an adverse effect on the treated subjects 

was identified). Additionally, these 

articles do not advance specific 

evidence, or even arguments, 

concerning the Gledhill study itself. 

(See 53 FR 53176, 53179-53180 

(December 30, 1998) (a general assertion 

in a letter to Science magazine is not 

basis for a hearing); 68 FR 46403, 46405- 

46406 (August 5, 2003) (a hearing was 

denied because the cited studies only 

contained equivocal statements 

supporting the objector’s position)). 

NRDC also cites the variable level of 

cholinesterase inhibition within 

individuals as supporting its statistical 

power argument. NRDC references a 

different DDVP human study by 

Gledhill (MRID # 44248802) to show 

variability in cholinesterase inhibition. 

This argument and these data also do 

not justify a hearing. 

Initially, it must be noted that EPA 

cannot consider this other Gledhill 

study because both EPA and the HSRB 

concluded it was without scientific 

merit and therefore does not qualify for 

EPA consideration under the Human 

Research rule. (Ref. 21 at 42-43). 

Whether or not the aspect of the study 

cited by NRDC is implicated by this 

conclusion has not been evaluated; 

nonetheless, EPA does not disagree with 

NRDC’s assertion that individual 

humans have variable levels of 

cholinesterase inhibition and thus this 

is not a disputed issue of fact. Neither 

does EPA dispute that variability of 

cholinesterase inhibition should be 

taken into account in considering 

statistical power and in analyzing the 

results of a human study. 

However, as discussed above, 

statistical power is no longer a relevant 

concept once EPA has concluded that a 

toxicity study shows that the pesticide 

has an adverse effect on treated subjects. 

Statistical power is a tool used to 

evaluate the possibility of accepting 

false negatives. Moreover, the variability 


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of cholinesterase inhibition in subjects 

is also a factor relating to a concern with 

false negatives. Normal variation in the 

responses of individual test subjects 

may mask treatment-related effects 

leading to a false conclusion that there 

were no treatment-related effects. 

Finally, NRDC’s claims on variability 

amount to no more than a mere 

allegation that the existence of variable 

rates of cholinesterase inhibition 

indicate a flaw in the Gledhill study and 

EPA’s reliance on it. Without an 

evidentiary proffer, however, a hearing 

is not appropriate. 

iv. Denial of objection. NRDC has 

misconstrued the concept of statistical 

power. It has little relevance in 

circumstances where a positive effect is 

found in a toxicological study. NRDC’s 

objection that EPA should not have 

relied upon the Gledhill study because 

it lacked statistical power is denied. 

b. Too few test subjects to establish a 

NOAEL—i. Objection/hearing request. 

NRDC objects to reliance on the Gledhill 

study claiming that because it only 

involved six treated test subjects it 

cannot ‘‘support the establishment of a 

reliable NOAEL or dose response curve 

. . . .’’ (Ref. 1 at 13). 

ii. Background. NRDC’s claim was 

contained in both its petition and its 

comments on the IRED. (Refs. 1 at 26; 

and 23 at 15). In its petition denial 

order, EPA responded to these claims by 

concurring with the HSRB’s conclusion 

that the Gledhill study was ‘‘sufficiently 

robust for developing a Point of 

Departure for estimating dermal, 

incidental oral, and inhalation risk from 

exposure to DDVP in a single chemical 

assessment.’’ (72 FR at 68675 (quoting 

HSRB Report)). The HSRB found the 

study to be ‘‘robust’’ based on the 

following attributes: ‘‘the repeated dose 

approach which allowed examination of 

the sustained nature of RBC 

cholinesterase inhibition; robust 

analysis of RBC cholinesterase 

inhibition both in terms of identifying 

pre-treatment levels and consistency of 

response within and between subjects; 

and the observation of a low, but 

statistically significant RBC 

cholinesterase inhibition response.’’

(Id.; Ref. 21 at 39-41). 

iii. Denial of hearing. NRDC has not 

met the requirements for a hearing on 

this sub-issue. First, NRDC has proffered 

no evidence that the six treated subjects 

in the Gledhill subject were too few for 

EPA to use data from that study as a 

Point of Departure. Rather, NRDC does 

no more than state ‘‘[w]e are aware of 

no statistical test’’ which would support 

EPA’s use of the Gledhill data. (Ref. 1 

at 13). As EPA’s regulations make clear, 

a mere ‘‘denial’’ of an EPA position is 

not sufficient to satisfy the standard for 

granting a hearing. (40 CFR 

178.32(b)(2)). Second, NRDC does not 

confront the reasoning of the HSRB, 

which was adopted by EPA, for why the 

data from the Gledhill study are 

sufficiently robust to justify their use as 

a Point of Departure. This failure to 

challenge the basis of EPA’s petition 

denial affects the materiality of the 

objection and hearing request. Even if 

NRDC could demonstrate in a hearing 

that generally more test subjects are 

needed to derive a Point of Departure 

for a RfD/PAD, that evidence would not 

address the specific factors in the 

Gledhill study that EPA and the HSRB 

found convincing on this question. (See 

Unit VIII.D.4.a.iii). 

iv. Denial of objections. EPA does not 

agree with NRDC’s undocumented 

assertion that the Gledhill study does 

not provide an appropriate Point of 

Departure for assessing DDVP risk. EPA, 

and the HSRB, found that there were 

several features of the study and the 

statistical analysis of the study that 

made it ‘‘sufficiently robust for 

developing a Point of Departure . . . .’’

(72 FR at 68675). Important factors cited 

by the HSRB, and adopted by EPA, 

included: (1) the study design which 

involved repeated dosing and repeated 

measurement of cholinesterase effects in 

individuals; (2) extensive pre-dosing 

measurement of the test subjects’

cholinesterase inhibition levels which 

showed consistency both within and 

between individual test subjects; and (3) 

the clear study results which showed a 

statistically significant effect on 

cholinesterase inhibition was found 

(both between controls and treated 

subjects and between the tested 

subjects’ pre- and post-dosing levels) 

that was at or near the lowest level that 

could be distinguished from baseline 

values. (72 FR at 68675). Further, as 

EPA noted in its petition denial order, 

a similar number of test subjects (four 

per sex) are recommended for a 

toxicology study in non-rodents (usually 

the dog) routinely required for pesticide 

risk assessment. (72 FR at 68675). 

In response to EPA’s and the HSRB’s 

conclusions as to the Gledhill study, 

NRDC does little more than repeat its 

allegation that the Gledhill study was 

underpowered. NRDC does respond to 

EPA’s reference to the chronic dog 

study, alleging without providing any 

basis that that study is underpowered, 

and claiming that ‘‘EPA rarely relies 

upon that study.’’ (Ref. 1 at 13). NRDC 

is incorrect. The chronic dog study was 

added to EPA’s testing requirement 

regulations in 1984 and was included in 

the revised regulations re-promulgated 

just last year, although the length of the 

study was shortened from 1 year to 13 

weeks. (72 FR 60934, 60940-60941 

(October 26, 2007); 49 FR 42881 

(October 24, 1984)). As a standard study 

required in evaluating pesticides used 

on food, the chronic dog study would 

have been considered and relied upon 

in virtually every one of the roughly 

10,000 FFDCA tolerance reassessments 

conducted in the 10 years following 

enactment of the FQPA. (Ref. 37). If, by 

‘‘rarely relied upon,’’ NRDC means the 

results from chronic dog are rarely used 

as a Point of Departure, NRDC is still 

incorrect. For example, a cursory review 

of rules establishing new tolerances in 

2005 showed at least eight instances in 

which the Point of Departure for 

assessment of a pesticide’s risk was 

based on the chronic dog study. (70 FR 

77363, 77366 (December 30, 2005) 

(hexythiazox); 70 FR 74688, 74690 

(December 16, 2005) (bifenazate); 70 FR 

55740, 55743 (September 23, 2005) 

(fenpropathrin); 70 FR 55752, 55757 

(September 23, 2005) (amicarbazone); 70 

FR 55761, 55764 (September 23, 2005) 

(pyridaben); 70 FR 54640, 54644 

(September 16, 2005) (fluoxastrobin); 70 

FR 53944, 53946 (September 13, 2005); 

70 FR 51615, 51617 (August 31, 2005) 

(halosulfuron-methyl). A retrospective 

analysis performed by EPA in 2005 also 

showed that 116 out of 304 chronic RfDs 

for pesticides was based on the chronic 

dog study. (Ref. 38). Finally, another 

example somewhat closer to home 

would be DDVP, where the NOAEL 

from the chronic dog study is used as 

the Point of Departure in assessing 

chronic dietary risk. (Ref. 3 at 132). 

Further, EPA’s recommendation for 

four test subjects per sex per dose in the 

sub-chronic and chronic non-rodent 

(dog) study is widely followed. The 

FDA has a similar recommendation for 

conducting non-rodent studies of subchronic and chronic duration as does 

the Organisation for Economic Cooperation and Development (‘‘OECD’’), 

Canada which has accepted the OECD 

guideline on the sub-chronic and 

chronic non-rodent (dog) study, and the 

European Commission’s Joint Research 

Centre of the European Union. (Refs. 39, 

40, 41, 42, and 43). 

c. Adult males only—i. Objection/ 

hearing request sub-issue. NRDC objects 

to the Gledhill study because it 

included as test subjects only adult 

males. (Ref. 1 at 14). NRDC claims that 

adult males are ‘‘biologically 

unrepresentative’’ of the human 

population. 

ii. Background. NRDC’s objection is 

drawn verbatim from its comments on 

the DDVP IRED. EPA responded to this 

argument by pointing out that ‘‘no sex 

differences were observed in the 


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comparative cholinesterase studies.’’ (72 

FR at 68675). EPA also found no agerelated differences in cholinesterase 

inhibition. (72 FR at 68694). 

iii. Denial of hearing. A hearing is 

denied on this sub-issue because there 

is no disputed factual matter for 

resolution at a hearing. There is no 

dispute concerning the subjects in the 

Gledhill study - they were adult males. 

Thus, the only question is whether a 

human study using only adult males 

meets the regulatory requirement of 

‘‘scientifically valid and relevant data.’’

(40 CFR 26.1701). Because NRDC has 

proffered no evidence regarding the 

representativeness of adult males to the 

general population, this question 

requires the application of a legal 

standard to undisputed facts. Hearings 

are not appropriate on questions of law 

or policy. (40 CFR 178.32(b)(1)). FDA 

has repeatedly confirmed that the 

application of a legal standard to 

undisputed facts is a question of law for 

which a hearing is not required. (See, 

e.g., 68 FR 46403, 46406 n.18, 46408, 

46409 (August 5, 2003) (whether facts in 

the record show there is a reasonable 

certainty of no harm is a question of 

law; whether a particular effect is a 

‘‘harm’’ is a question of law)). 

NRDC’s hearing request is also flawed 

because NRDC does not object to the 

basis EPA asserted in its petition denial 

for concluding that the Gledhill study 

provided scientifically valid data 

despite its use of only adult male 

subjects. As noted above, EPA thought 

representativeness concerns were 

addressed by the fact that animal 

studies with DDVP showed no 

differences in sensitivities between 

males and females and adults and the 

young. NRDC, however, has not 

challenged and proffered evidence to 

rebut this conclusion nor has NRDC 

challenged or proffered evidence to 

rebut EPA’s analysis of the underlying 

data. Rather, NRDC just repeats its 

assertions regarding the 

unrepresentativeness of adult males 

generally. This failure to challenge the 

basis of EPA’s petition denial affects the 

materiality of the objection and hearing 

request. Even if NRDC offers evidence to 

show sex- and age-related sensitivities 

in the population to some toxicants, 

such evidence would not rebut the 

DDVP-specific data on sensitivity. (53 

FR 53176, 53191 (December 30, 1988) 

(FDA denied a hearing request noting 

that given FDA’s prior conclusion that 

the studies relied upon by the objector 

were unreliable, the ‘‘burden shifted to 

[the objector] to maintain the viability of 

its objection by proffering some 

information that called into question the 

agency’s conclusion on this matter.’’)). 

iv. Denial of objection. EPA concludes 

that it was reasonable to use the 

Gledhill study despite that fact that it 

only examined adult males given that 

the animal toxicology data on DDVP’s 

cholinesterase effects consistently 

showed no differences between males 

and females and adults and the young. 

Multiple studies involving adult 

animals yielded consistent 

cholinesterase inhibition results in 

males and females. (Ref. 3 at 124-126). 

Similarly, Benchmark Dose Method 

analysis of the developmental 

neurotoxicity data ‘‘did not demonstrate 

any substantial numerical differences in 

[Benchmark Dose Method Level] values 

for either RBC or brain cholinesterase 

between young and adult animals.’’ (72 

FR at 68694). 

d. Plasma—i. Objection/hearing 

request. NRDC objects that the Gledhill 

study is unreliable because it measured 

only RBC cholinesterase inhibition and 

not plasma cholinesterase inhibition. 

NRDC claims that measuring plasma 

cholinesterase might have reduced the 

variability measured in RBC 

cholinesterase. 

ii. Background. In its petition, NRDC 

argued that plasma cholinesterase 

should have been measured because it 

might be a more sensitive indicator of 

DDVP’s cholinesterase effects. EPA 

responded to the petition by noting that 

RBC cholinesterase is the Agency’s 

preferred cholinesterase inhibition 

endpoint as compared to plasma 

cholinesterase. (72 FR at 68676). EPA 

explained that ‘‘[s]ince the red blood 

cell contains only acetylcholinesterase, 

the potential for exerting effects on 

neural or neuroeffector 

acetylcholinesterase may be better 

reflected by changes in red blood cell 

acetylcholinesterase than by changes in 

plasma cholinesterases which contain 

both butyrylcholinesterase and 

acetylcholinesterase in varying ratios 

depending upon the species.’’ (Id.). EPA 

concluded that information on a less 

preferred endpoint ‘‘adds little 

meaningful information.’’ (Id.). 

iii. Denial of hearing. NRDC proffers 

no evidence in support of its allegation 

that collection of plasma cholinesterase 

inhibition data would be useful in 

limiting the variability seen in the RBC 

cholinesterase inhibition data. Hearings 

will not be granted on mere allegations. 

(40 CFR 178.32(b)(2)). Further, given 

EPA’s conclusion that the variability in 

RBC cholinesterase inhibition in the test 

subjects was accounted for by pre- and 

post-treatment measurement, this issue 

is not material to resolution of NRDC’s 

claim. Finally, to the extent NRDC is 

advocating reliance on plasma 

cholinesterase inhibition data over RBC 

cholinesterase inhibition data that is a 

policy issue and hearings will not be 

held as to policy issues. (40 CFR 

178.32(b)(1)). 

iv. Denial of objection. EPA’s wellestablished policy when evaluating 

blood cholinesterase inhibition is to use 

RBC cholinesterase data in preference to 

plasma cholinesterase. (Ref. 10 at 32). 

EPA’s reasoning here is straightforward. 

Blood cholinesterase data is used as an 

indicator of possible effects on 

acetylcholinesterase in the peripheral 

nervous system. RBC cholinesterase is 

composed entirely of 

acetylcholinesterase, whereas plasma 

cholinesterase is a mixture of 

acetylcholinesterase and 

butyrylcholinesterase, a compound 

somewhat similar to 

acetylcholinesterase in structure that 

nonetheless is ‘‘different in important 

ways which often result in it having 

binding affinities to anticholinesterase 

agents as well as other characteristics 

that are quite different from those of 

acetylcholinesterase.’’ (Id. at 32). The 

ratio of acetylcholinesterase to 

butyrylcholinesterase in plasma differs 

by species; in humans, plasma ‘‘is 

overwhelmingly butyrylcholinesterase 

with a ratio of butyrylcholinesterase to 

acetyl cholinesterase of 1,000:1.’’ (Id.) 

It is preferable to have both RBC and 

plasma cholinesterase data from a study 

because effects in the RBC may be nonexistent, equivocal, or fail to establish a 

clear-dose response pattern. In those 

circumstances, plasma cholinesterase 

inhibition data may serve as a Point of 

Departure or may aid in the 

interpretation of the RBC data, 

particularly when extrapolating animal 

data to humans. In the Gledhill study, 

however, the robust RBC cholinesterase 

sampling approach in humans (multiple 

pre- and post-dosing samples and 

sampling after repeat dosing) as well as 

the clear pattern on RBC cholinesterase 

inhibition means the absence of plasma 

cholinesterase inhibition data is of little 

to no consequence. 

In its objections NRDC claims that 

plasma cholinesterase inhibition data 

‘‘might have reduced somewhat’’ the 

variability in the RBC cholinesterase 

data. EPA disagrees both because 

plasma cholinesterase in humans is 

overwhelmingly composed of 

butyrylcholinesterase not 

acetylcholinesterase, and because the 

robust sampling plan in the Gledhill 

study well-characterized the RBC 

cholinesterase variability. For all of 

these reasons, NRDC’s objection on this 

issue are denied. 

e. Controls over environment—i. 

Objection/hearing request sub-issue. 

NRDC argues that because there were 


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not controls over the Gledhill test 

subjects’ exposure to environmental 

factors which might affect 

cholinesterase inhibition (e.g., ingestion 

of pharmaceuticals), the results of 

Gledhill study might be caused 

environmental factors and are thus 

invalid. 

ii. Background. This claim is 

contained in NRDC’s petition and was 

not specifically addressed by EPA in the 

petition denial order other than through 

its acceptance of the HSRB’s analysis. 

iii. Denial of hearing request. The 

control measures used in the Gledhill 

study are set forth in the study report 

and are not in dispute. The only 

question is whether these control 

measures make the Gledhill study 

scientifically invalid and thus not in 

compliance with EPA regulations. Legal 

questions such as this are not 

appropriate for a hearing. (40 CFR 

178.32(b)(1); see, e.g., 68 FR 46403, 

46406 n.18, 46408, 46409 (August 5, 

2003) (whether facts in the record show 

there is a reasonable certainty of no 

harm is a question of law and thus is not 

a hearing issue; whether a particular 

effect is a ‘‘harm’’ is a question of law 

not of fact and a hearing will not be held 

on issues of law)). Additionally, NRDC 

proffers no evidence regarding the effect 

of the study’s control measures other 

than speculation about how 

environmental factors might have 

affected the study. A hearing will not be 

granted on the basis of mere allegations 

or speculation. (40 CFR 178.32(b)(2); (57 

FR 6667, 6671 (February 27, 1992)). 

Finally, NRDC’s argument here is 

immaterial to its claim. As EPA explains 

below in denying this objection, the lack 

of control measures would only be an 

issue if NRDC is arguing that EPA has 

wrongfully concluded that the Gledhill 

study has not shown a measurable effect 

in the treated subjects. 

iv. Denial of objection. NRDC’s 

objection here might warrant some 

consideration if the study results had 

shown no pattern and EPA had 

concluded that the study established a 

NOAEL for DDVP. In those 

circumstances, it could be argued that 

any effects from DDVP exposure may 

have been masked by other factors. 

However, the study results here showed 

a clear and consistent pattern of 

marginal effects on RBC cholinesterase 

inhibition in connection with DDVP 

dosing. Given these results and the fact 

that the test subjects were pre-screened 

for environmental factors that might 

affect study results (e.g., regular use of 

pharmaceuticals; excessive alcohol 

consumption; exposure to 

organophosphurus compounds), 

NRDC’s speculation that environmental 

factors might have affected the study 

results is without merit. 

f. Consent—i. Objection/hearing 

request sub-issue. NRDC asserts that 

informed consent was not obtained from 

the Gledhill test subjects because the 

consent form for the experiment 

identified DDVP as a ‘‘drug.’’ (Ref. 1 at 

14). NRDC claims that EPA has ignored 

this issue. NRDC cites an EPA 

memorandum dated March 16, 2006, 

examining the ethics of the Gledhill 

study and asserts that it ‘‘fails to 

mention [the informed consent] issue 

when it concludes that the study was 

not fundamentally unethical.’’ (Id. at 

15). NRDC argues that describing DDVP 

as a drug ‘‘constitute[s] ‘fundamentally 

unethical’ actions by any reasonable 

understanding of that term.’’ (Id.). 

ii. Background. This objection comes 

verbatim from NRDC’s comments on the 

DDVP IRED. EPA responded to this 

issue in its denial of NRDC’s petition by 

adopting the HSRB’s conclusion that 

informed consent was obtained. EPA 

explained that ‘‘[t]he HSRB reasoned 

that references to DDVP as a drug did 

not vitiate informed consent because 

‘the consent materials clearly advised 

subjects that this was a study involving 

consuming an insecticide.’’’ (72 FR at 

68675). 

iii. Denial of hearing. It is not clear 

from NRDC’s objections whether NRDC 

is challenging EPA’s conclusion on the 

ethics of consent issue based on (1) an 

alleged failure of EPA to address this 

question; or (2) the legal proposition 

that identification of a pesticide as a 

drug ‘‘constitute[s] ‘fundamentally 

unethical’ actions by any reasonable 

understanding of that term.’’ In either 

case, a hearing is not appropriate on 

NRDC’s objection. 

First, NRDC’s allegation that EPA did 

not address the consent issue does not 

present a genuinely-disputed issue of 

fact. It is plain on the face of EPA’s 

petition denial order, that EPA adopted 

the reasoning of the HSRB on why 

references on the consent form to DDVP 

as a drug do not constitute clear and 

convincing evidence that the Gledhill 

study is fundamentally unethical. (72 

FR at 68675). After summarizing the 

decision of the HSRB on the consent 

issue (see quoted language in Unit 

VIII.E.3.f.ii. above), EPA stated: ‘‘EPA 

adopts the HSRB’s reasoning and finds 

it persuasive in rejecting NRDC’s 

arguments concerning why the Gledhill 

study should not be relied upon.’’ (Id.). 

NRDC’s argument that EPA offered no 

explanation is based on a memorandum 

that predates and is superseded by 

EPA’s denial of NRDC’s petition. The 

March 16, 2006 memorandum was 

finalized more than 20 months before 

issuance of the DDVP petition denial 

order and the order contains EPA’s 

rationale on the consent issue. As noted 

earlier in Unit VIII.D.3.c., when an 

objector to a section 408(d)(4)(iii) order 

challenges an EPA conclusion that has 

been superseded by the section 

408(d)(4)(iii) order, the objector has not 

raised a live controversy as to a material 

issue. (See 53 FR 53176, 53191 

(December 30, 1988) (where FDA 

responds to a comment in the final rule, 

repetition of the comment in objections 

does not present a live controversy 

unless the objector proffers some 

evidence calling FDA’s conclusion into 

question)). Moreover, objections, and 

hearing requests on objections, may 

only be filed as to a section 408(d)(4)(iii) 

order or other statutorily-specified 

action. (21 U.S.C. 346a(g)(2)(A)). 

Second, the informed consent 

question as to the Gledhill study is a 

legal/policy issue not a factual one. 

There are no disputed facts regarding 

the consent form. The consent form 

used in the Gledhill study is set forth in 

the study report and NRDC has not 

proffered any other evidence bearing on 

consent. Accordingly, the only question 

is the legal/policy one of whether use of 

the Gledhill study consent form is 

‘‘clear and convincing evidence’’ that 

the Gledhill study was ‘‘fundamentally 

unethical’’ and thus not in compliance 

with EPA regulations. (40 CFR 26.1704). 

In fact, NRDC has framed the consent 

issue as a legal question, arguing that 

the undisputed reference to DDVP as a 

drug in the consent form for the Gledhill 

study ‘‘constitute[s] [a] ‘fundamentally 

unethical’ action[] by any reasonable 

understanding of that [regulatory] 

term.’’ (Ref. 1 at 15). Further, to support 

this legal argument, NRDC turns to other 

legal authorities arguing that ‘‘[t]he 

requirement for obtaining informed 

consent is at the core of the [40 CFR] 

Part 26 regulations and FIFRA section 

12(a)(2)(P),’’ and ‘‘[v]iolation of these 

regulations, laws and international 

standards in the design and conduct of 

human studies is fundamentally 

unethical.’’ (Id.). Hearings are not 

appropriate on questions of law or 

policy. (40 CFR 178.32(b)(1)). 

Finally, a hearing is not appropriate 

on this sub-issue because NRDC’s 

objection does not respond to EPA’s 

conclusion, based on the HSRB’s 

reasoning, as to why there was not a 

problem with consent in the Gledhill 

study. As such, NRDC’s objection on 

this point is nothing more than a general 

denial of EPA’s conclusion and a 

hearing cannot be justified on this basis. 

(40 CFR 178.32(b)(2)). 

iv. Denial of objection. NRDC has 

offered no response to EPA’s petition 


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denial order which incorporated the 

HSRB’s reasoning as to why the 

references to DDVP as a drug did not 

constitute clear and convincing 

evidence that the Gledhill study was 

fundamentally unethical. Specifically, 

NRDC does not address the HSRB’s 

conclusion, adopted by EPA, that the 

test subjects’ consent was informed 

because ‘‘the consent materials clearly 

advised subjects that this was a study 

involving consuming an insecticide.’’

(Ref. 21 at 46). Thus, EPA denies the 

objection. 

g. Protection of health of the test 

subjects—i. Objection/hearing request 

sub-issue. NRDC differs with EPA’s 

conclusion that there was not clear and 

convincing evidence that the Gledhill 

study was rendered fundamentally 

unethical by the failure of the test 

conductors to retest the subjects until 

their cholinesterase inhibition levels 

returned to baseline levels. (Ref. 1 at 14- 

15). According to NRDC, EPA 

acknowledged, in a March 16, 2006, 

memorandum, that the failure to retest 

was inconsistent with the standards in 

the Declaration of Helskinki by showing 

a lack of concern for the safety of the 

test subjects. (Id.). NRDC claims that 

EPA has offered no explanation for why 

it concluded that the Gledhill study was 

not fundamentally unethical despite 

this inconsistency with the Declaration 

of Helsinki. (Id. at 15). 

ii. Background. This objection is 

adopted verbatim from the comments 

that NRDC filed on the IRED. (Ref. 23 at 

16-17). In responding to this claim, EPA 

adopted the reasoning of the HSRB that 

‘‘[d]eficiencies in monitoring of subjects 

were found not to provide clear and 

convincing evidence that the study was 

ethically deficient by subjecting the test 

subjects to the threat of serious harm 

because prior studies by this researcher 

involving higher doses had only 

invoked minimal responses.’’ (72 FR at 

68675). 

iii. Denial of hearing. As with the 

consent issue, it is not clear from 

NRDC’s objections whether NRDC is 

challenging EPA’s conclusion on the 

ethics of not retesting based on (1) an 

alleged failure of EPA to offer an 

explanation for its conclusion; or (2) the 

legal proposition that a study that is 

inconsistent with the Declaration of 

Helsinki is necessarily ‘‘fundamentally 

unethical’’ under the Human Research 

rule. In either case, a hearing is not 

appropriate on NRDC’s objections. 

If NRDC is challenging EPA’s alleged 

lack of an explanation, then NRDC has 

failed to identify a genuinely-disputed 

issue of fact. As with the consent issue, 

EPA, in its petition denial order, 

summarized and then adopted the 

reasoning of the HSRB on why the 

failure to retest does not constitute clear 

and convincing evidence that the 

Gledhill study is fundamentally 

unethical. (72 FR at 68675) (see quoted 

language in Unit VIII.E.3.g.ii. above). 

NRDC’s argument that EPA offered no 

explanation is based on a memorandum 

that predates and is superseded by 

EPA’s denial of NRDC’s petition. For the 

reasons set forth in Unit VIII.D.3.c and 

Unit VIII.E.3.f.iii., an objection and 

hearing request as to a section 

408(d)(4)(iii) order based on a 

memorandum superseded by the section 

408(d)(4)(iii) order does not constitute a 

live controversy on an issue material to 

the section 408(d)(4)(iii) order and, 

arguably, not even a valid objection 

under section 408(g)(2)(A). (21 U.S.C. 

346a(g)(2)(A); see 53 FR 53176, 53191 

(December 30, 1988) (where FDA 

responds to a comment in the final rule, 

repetition of the comment in objections 

does not present a live controversy 

unless the objector proffers some 

evidence calling FDA’s conclusion into 

question)). 

If NRDC is challenging the substance 

of EPA’s conclusion on the ethics of the 

Gledhill study, this objection also does 

not warrant a hearing because NRDC is 

making no more than a legal or policy 

argument. There is no dispute with 

regard to what post-testing was 

performed as to the Gledhill subjects. 

NRDC admits as much. (Ref. 1 at 15 

(‘‘There is nothing in the [EPA] memo 

that suggests that there is any 

uncertainty or controversy about what 

the various study documents said or 

what was done in the study in relation 

to this ethical ‘inconsistency’ with the 

Helsinki Declaration. . . . 

Notwithstanding the clear facts of the 

case [regarding retesting] . . . .’’). The 

only question is whether the failure to 

test subjects until cholinesterase 

inhibition levels returned to baseline is 

‘‘clear and convincing evidence’’ that 

the Gledhill study was ‘‘fundamentally 

unethical.’’ (40 CFR 26.1704). Like the 

consent issue, NRDC, itself, has framed 

the issue as involving a legal question 

as to which there is only one answer. 

According to NRDC, ‘‘these failings [as 

to retesting subjects and consent] both 

constitute ‘fundamentally unethical’

actions by any reasonable 

understanding of that term.’’ (Ref. 1 at 

15). Further, NRDC argues categorically 

that ‘‘[v]iolation of . . . international 

standards in the design and conduct of 

human studies is fundamentally 

unethical.’’ (Id.). This is a legal/policy 

determination regarding application of 

an EPA regulatory standard and the 

standards of the Declaration of Helsinki 

to undisputed facts. Certainly, NRDC 

has proffered no genuine factual issue to 

be resolved at a hearing. Hearings are 

not appropriate on questions of law or 

policy. (40 CFR 178.32(b)(1)). 

Finally, a hearing is not appropriate 

on this sub-issue because NRDC’s 

objection does not respond to EPA’s 

conclusion, based on the HSRB’s 

reasoning, as to why the failures in 

monitoring of subjects following the 

conclusion of dosing did not amount to 

clear and convincing evidence that the 

study was fundamentally unethical. As 

such, NRDC’s objection on this point is 

nothing more than a general denial of 

EPA’s conclusion and a hearing cannot 

be justified on this basis. (40 CFR 

178.32(b)(2)). 

iv. Denial of objection. NRDC has 

offered no response to EPA’s petition 

denial order which incorporated the 

HSRB’s reasoning as to why the failure 

to retest subjects did not constitute clear 

and convincing evidence that the 

Gledhill study was fundamentally 

unethical. Specifically, NRDC does not 

address the HSRB’s conclusion, adopted 

by EPA, that the lack of retesting was 

not fundamentally unethical because 

‘‘prior studies by this researcher 

involving higher doses had only 

invoked minimal responses.’’ (72 FR at 

68675). Thus, NRDC’s objection on this 

point is denied. 

F. Summary of Reasons for Denial of 

NRDC’s Hearing Requests 

EPA denies NRDC’s request for a 

hearing on whether reliable data 

support EPA’s reduction of the 

children’s safety factor and on whether 

EPA properly relied on the Gledhill 

human study. EPA’s close examination 

of each of the 19 sub-issues involved in 

these two hearing requests demonstrates 

that none of the issues satisfies the 

standard for granting a hearing in 40 

CFR 178.32. Most fail for multiple 

reasons. 

Several sub-issues do not present an 

issue of genuinely-disputed fact. 

Instead, NRDC raises issues presenting 

purely legal or policy questions or 

questions involving the application of 

legal standards to undisputed facts. For 

example, with regard to its children’s 

safety factor objection, NRDC makes the 

legal argument that failure to complete 

the mandatory endocrine screening 

program compels EPA to retain the 

children’s safety factor for DDVP and all 

other pesticides. (See Unit VIII.D.2.a.). 

In other cases, NRDC’s description of a 

factual dispute is clearly contradicted 

by the record. An example here is 

NRDC’s assertion that EPA failed to 

consider acute residential exposure 

even though EPA, in response to 


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NRDC’s petition, amended its risk 

assessment to include examination of 

exposure for 1–day and 14–day periods. 

(See Unit VIII.D.4.c.) 

Many of NRDC’s sub-issues lack 

materiality. In some instances that is 

due to NRDC’s misunderstanding of a 

scientific concept - as when NRDC 

raises questions about the statistical 

power of the Gledhill study or seeks to 

invalidate the Gledhill study based on a 

alleged inadequacy to control for 

environmental factors. Both of these 

concepts have little relevance given the 

positive results found in that study. (See 

Units VIII.E.3.a. and VIII.E.3.e.). In other 

instances, the sub-issues presented by 

NRDC lack materiality either because (1) 

NRDC objects to aspects of EPA’s risk 

assessments that were changed in 

response to the petition; (2) NRDC fails 

to address the reasons given by EPA for 

denying NRDC’s petition; or (3) NRDC 

objects to prior conclusions of EPA that 

were superseded by the petition denial 

order. (See Units VIII.D.3., VIII.E.3.b., 

and VIII.E.3.g.) 

Most importantly, as to all of the subissues, NRDC fails to identify and 

proffer evidence which, if established, 

would resolve one or more questions in 

NRDC’s favor. As EPA’s analysis shows, 

NRDC essentially proffered no evidence 

in support of its hearing requests and 

objections and instead relies upon legal 

and policy arguments and unsupported 

or speculative factual assertions. 

NRDC’s attempted evidentiary proffers 

are either: (1) so broad as to be 

meaningless (e.g., the complete EPA 

docket for DDVP); (2) too general to 

define a factual issue as to DDVP (e.g., 

newspaper and law review articles); (3) 

supportive of scientifically irrelevant 

claims (e.g., Sass and Lockwood 

articles); or (4) mere allegations or 

general denials (e.g., NRDC’s claim that 

dietary risk assessment ‘‘poses a serious 

risk of understating risks posed by 

DDVP;’’ NRDC’s speculation about how 

many DDVP pest strips a homeowner 

may use). (See Units VIII.C., VIII.D.3., 

and VIII.D.4.e.). 

NRDC’s failure to offer evidence in 

support of its contentions is a consistent 

pattern in this proceeding. NRDC 

offered no greater support for its 

arguments in its petition, in its 

comments on the IRED, or, for that 

matter, in its written or oral comments 

to the HSRB. In these circumstances, 

EPA questions whether granting a 

hearing would have been appropriate 

even if NRDC had, at this last stage of 

the administrative process, suddenly 

produced factual evidence in support of 

its claims. Presumably, Congress created 

a multi-stage administrative process for 

resolution of tolerance petitions to give 

EPA the opportunity in the first stage of 

the proceeding to resolve factual issues, 

where possible, through a notice-andcomment process, prior to requiring 

EPA to hold a full evidentiary hearing 

- which can involve a substantial 

investment of resources by all parties 

taking part. While EPA has not held any 

pesticide tolerance hearings under the 

FFDCA, its experience with pesticide 

hearings under FIFRA in the 1970s 

indicates the process can be quite 

lengthy. (See were e.g., Environmental 

Defense Fund v. EPA, 548 F.2d 998, 

1002 (D.C. Cir. 1976) (4 months were 

needed for testimony in an expedited 

FIFRA suspension proceeding); 

Environmental Defense Fund, Inc. v. 

EPA, 510 F.2d 1292, 1297 (D.C. Cir. 

1975) (13 months of testimony in a 

FIFRA cancellation proceeding); 

Environmental Defense Fund v. 

Ruckelshaus, 489 F.2d 1247, 1251 n. 24 

(D.C. Cir. 1973) (‘‘During seven months 

of hearings [in the DDT cancellation 

proceeding], 125 witnesses appeared to 

testify and 365 exhibits were placed in 

evidence. The transcript of the hearings 

was over 9,000 pages long.’’); Ref. 44 at 

246 (referring to FIFRA cancellation 

proceedings in the 1970s as the ‘‘‘100–

years’ pesticide wars’’). Given that in 

the ensuing 30 years the pesticide risk 

assessment process has become 

exponentially more complex, FFDCA 

pesticide hearings have the potential for 

being even more resource intensive. 

Accordingly, if a party were to withhold 

evidence from the first stage of a 

tolerance petition proceeding and only 

produce it as part of a request for a 

hearing on an objection, EPA might very 

likely determine that such an untimely 

submission of supporting evidence 

constituted an amendment to the 

Original petition requiring a return to 

the first stage of the administrative 

process (if, consideration of information 

that was previously available is 

appropriate at all). 

Finally, EPA notes that it is denying 

NRDC’s hearing requests under 40 CFR 

178.32 and does not here rely on the 

even broader discretionary authority to 

deny hearing requests in FFDCA section 

408(g)(2)(B). As recounted previously, 

40 CFR 178.32 predates the explicit 

addition to the statute by the FQPA of 

the grant of authority to EPA to deny 

hearings. That language 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 does not 

interpret this language as requiring it to 

hold a hearing in any instance where 

factual evidence relevant to a material 

issue of fact is proffered (essentially the 

standard set forth in 40 CFR 178.32); 

rather, EPA construes the statutory 

language as requiring it to hold a 

hearing only where it determines a 

hearing is necessary to receive such 

proffered evidence. In other words, a 

party wishing to obtain a hearing must 

not only satisfy the requirements of 40 

CFR 178.32, it must also show that an 

evidentiary hearing is necessary to 

presentation of proffered evidence to the 

Agency. Because, however, NRDC has 

not satisfied the standard set forth in 40 

CFR 178.32, EPA does not need to 

address whether a hearing is necessary 

to receive NRDC’s ‘‘evidentiary’’ proffer. 

G. Summary of Reasons for Denial of 

NRDC’s Objections 

EPA denies NRDC’s objections to 

EPA’s petition denial that EPA lacked 

sufficient data to reduce the children’s 

safety factor for DDVP, and EPA 

unlawfully relied on the Gledhill 

intentional human dosing study in 

assessing the risk of DDVP exposure. 

1. Children’s safety factor objection. 

In support of its children’s safety factor 

objection, NRDC claims that EPA has 

inadequate data on endocrine effects, 

dietary exposure to DDVP residues in 

food, and exposure from residential pest 

strips. On endocrine effects, NRDC 

argues that EPA lacks adequate data, as 

a legal matter, because it has not 

completed the section 408(p) endocrine 

screening program, and, as a factual 

matter, because DDVP has not been 

tested under the most recent twogeneration rat reproduction study. EPA 

has previously rejected NRDC’s legal 

argument as not consistent with the 

statutory language, structure, or history, 

and NRDC has offered no arguments as 

to why EPA’s previous conclusion was 

incorrect. On the factual question of 

whether EPA has adequate endocrine 

data on DDVP, EPA concluded in the 

petition denial that, given the existing 

data bearing on DDVP’s potential to 

cause endocrine effects and large 

difference in sensitivity between 

DDVP’s cholinesterase inhibition effects 

and potential endocrine effects, EPA 

had sufficient reliable data on DDVP’s 

potential endocrine effects to vary from 

the default children’s safety factor. In its 

objections, NRDC offers nothing other 

than speculation about what another 

two-generation rat reproduction study 

might show. NRDC’s speculation does 

not convince EPA that its analysis was 

incorrect. 

As to dietary exposure to DDVP 

residues in food, NRDC argues that 

EPA’s dietary exposure assessment has 


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many shortcomings that may lead to 

underestimation of dietary exposure to 

DDVP. In support of this claim, NRDC 

relies on statements EPA made in 2000 

in a preliminary risk assessment of 

DDVP. NRDC places particular 

emphasis on its claim that EPA’s 

database on food consumption by 

infants is inadequate. These allegations 

by NRDC lack merit because NRDC has 

ignored the many revisions to the DDVP 

risk assessment since the 2000 

preliminary risk assessment. First, EPA 

completely revised the dietary exposure 

and risk assessment in response to 

NRDC’s petition. One of the specific 

reasons for revising the risk assessment 

was so that EPA’s latest information on 

infant food consumption could be 

incorporated. Second, also in response 

to NRDC’s petition, EPA 

comprehensively analyzed its dietary 

exposure assessment to evaluate 

whether that assessment potentially 

underestimated dietary exposure to 

DDVP. EPA concluded that ‘‘its 

assessment of exposure to DDVP from 

food will not under-estimate but rather 

over-estimate, and in all likelihood 

substantially over-estimate, DDVP 

exposure.’’ (72 FR at 68686). NRDC 

neither acknowledges nor challenges the 

revised dietary exposure assessment or 

EPA’s detailed analysis of whether that 

assessment under- or over-estimates 

DDVP exposure. Finally, EPA questions 

the materiality of NRDC’s argument 

with regard to DDVP exposure from 

food given that DDVP exposure from 

this source is trivial compared with 

other sources. For all of these reasons, 

EPA rejects NRDC’s arguments on the 

alleged inadequacy of EPA’s assessment 

of human dietary exposure to DDVP in 

food. 

With regard to DDVP exposure from 

residential pest strips, NRDC claims that 

the data relied upon by EPA (the Collins 

and DeVries study) was inadequate and 

EPA’s risk assessment based on that 

study was based on inadequatelysupported assumptions. These 

arguments, however, are without merit 

because not only does NRDC offer 

nothing other than general, 

undocumented contentions in support 

but once again NRDC has ignored clear 

evidence and analysis in the record that 

contradict its allegations. First, NRDC 

ignores the other DDVP pest strip 

exposure studies relied upon by EPA to 

support the findings in the Collins and 

DeVries study. EPA concluded that 

these studies confirmed that the 

findings in Collins and DeVries were 

representative of DDVP concentration 

levels from pest strips that could be 

expected in houses in other locations. 

Second, NRDC ignores EPA’s complete 

revision to the DDVP residential 

exposure assessment that was 

conducted in response to its petition. 

That revision modified numerous 

assumptions in the assessment to ensure 

that the data from the Collins and 

DeVries study were analyzed in a 

conservative fashion. NRDC does not 

acknowledge the new assessment much 

less offer a rebuttal to EPA’s revised 

analysis. Most surprisingly, NRDC 

repeats challenges to several 

assumptions (only examining DDVP 

exposure as averaged over a 120–day 

period; considering 16 hours per day a 

maximum exposure in a home) that 

were explicitly modified (adding 

consideration of 1–day and 14–day 

exposure periods; assuming 24 hours 

exposure per day) in the revised risk 

assessment in response to NRDC’s 

petition. Accordingly, EPA disagrees 

with NRDC’s allegations concerning the 

inadequacy of the data and assumptions 

underlying its residential pest strip risk 

assessment. 

2. Human study objection. NRDC 

challenged EPA’s reliance on the 

Gledhill human study arguing that 

EPA’s Human Research rule is unlawful 

and the study was both scientifically 

flawed and unethically conducted. 

NRDC relies on its legal briefs filed in 

a separate challenge to the Human 

Research rule and its comments on that 

rule in support of its legal attack on the 

rule. Similarly, to the extent NRDC has 

standing to challenge a rule whose 

‘‘primary concern’’ is the ‘‘[p]rotection 

of the health and safety of human test 

subjects,’’ (Ref. 1 at 15), EPA relies on 

its legal brief in the 2nd Circuit 

proceeding and the administrative 

record for the rule, in denying NRDC’s 

challenge to Human Research Rule. 

As to the Gledhill study, itself, NRDC 

makes various claims regarding its 

scientific validity and ethicality. NRDC 

has previously presented these claims in 

writing and orally to EPA’s HSRB. The 

HSRB is an independent scientific 

panel, consisting of experts in bioethics, 

biostatistics, human health risk 

assessment, and human toxicology, 

created specifically for the purpose of 

advising EPA on whether human 

studies have scientific value and 

conform to ethical standards. Although 

NRDC’s concerns as to the Gledhill 

study were presented to the HSRB, the 

HSRB concluded that the Gledhill study 

complied with the Human Research rule 

and could be considered by EPA in 

assessing the risk of DDVP. EPA relied 

heavily on the advice by the HSRB in 

denying NRDC’s petition. Remarkably, 

NRDC, in its objections, proceeds as if 

the HSRB review never occurred. NRDC 

neither acknowledges the existence of 

the HSRB report nor attempts to refute 

its reasoning. In Unit VIII.E. above, EPA 

repeats the findings of the HSRB and 

EPA’s reasons for accepting the HSRB’s 

conclusions with regard to the specific 

contentions of NRDC. Based on both the 

findings of the HSRB and EPA in its 

petition denial, as described above, as 

well as NRDC’s failure to meaningfully 

dispute those findings, EPA rejects 

NRDC’s challenge to EPA’s reliance on 

the Gledhill study. 

H. Conclusion 

For all of the reasons set forth above, 

EPA denies NRDC’s objections and its 

requests for a hearing on those 

objections. 

IX. References 

1. Natural Resources Defense Council, 

‘‘Objection to the Order Denying 

NRDC’s Petition to Revoke All 

Tolerances for Dichlorvos (DDVP), and 

Request for Public Evidentiary Hearing’’

(February 1, 2008). 

2. Natural Resources Defense Council, 

Petition of Natural Resources Defense 

Council To Conclude Special Review, 

Reregistration and Tolerance 

Reassessment Processes and To Revoke 

All Tolerances and Cancel All 

Registrations for the Pesticide DDVP 

(June 2, 2006). 

3. Office of Prevention, Pesticides and 

Toxic Substances, EPA, ‘‘Interim 

Reregistration Eligibility Decision for 

Dichlorvos (DDVP)’’ (June 2006). 

4. U.S. EPA, ‘‘A User’s Guide to 

Available EPA Information on Assessing 

Exposure to Pesticides in Food’’ (June 

21, 2000). 

5. Office of Pesticide Programs, US 

EPA, ‘‘Office of Pesticide Programs’

Policy on the Determination of the 

Appropriate FQPA Safety Factor(s) For 

Use in the Tolerance Setting Process’’

(February 28, 2002). 

6. U.S. EPA, ‘‘Residue Chemistry Test 

Guidelines: OPPTS 860.1500 Crop Field 

Trials’’ (August 1996). 

7. Office of Pesticide Programs, U.S. 

EPA and Pest Regulatory Management 

Agency, ‘‘Health Canada, NAFTA 

Guidance Document for Guidance for 

Setting Pesticide Tolerances Based on 

Field Trial Data’’ (September 28, 2005). 

8. Office of Pesticide Programs, U.S. 

EPA, ‘‘Choosing a Percentile of Acute 

Dietary Exposure as a Threshold of 

Regulatory Concern’’ March 16, 2000). 

9. Office of Pesticide Programs, U.S. 

EPA,‘‘Standard Operating Procedures 

(SOPs) for Residential Exposure 

Assessments’’ (Draft December 19, 

1997). 

10. Office of Pesticide Programs, U.S. 

EPA, ‘‘The Use of Data on 


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Cholinesterase Inhibition for Risk 

Assessments of Organophosphorous and 

Carbamate Pesticides’’ (August 18, 

2000). 

11. U.S. EPA, ‘‘Endocrine Disruptor 

Screening and Testing Advisory 

Committee Final Report’’ (August 1998). 

12. U.S. EPA, U.S. EPA Charter: 

Human Studies Review Board (2008) 

(available at http://www.epa.gov/osa/ 

hsrb/files/dated-hsrb-renewal-chartereffect-030408.pdf). 

13. Office of Pesticide Programs, U.S. 

EPA, ‘‘Organophosphorus Cumulative 

Risk Assessment – 2006 Update’’

(August 2006). 

14. Office of Prevention, Pesticides 

and Toxic Substances, EPA, 

Memorandum from Debra Edwards to 

Jim Jones, ‘‘Finalization of Interim 

Reregistration Eligibility Decisions 

(IREDs) and Interim Tolerance 

Reassessment and Risk Management 

Decisions (TREDs) for the 

Organophosphate Pesticides, and 

Completion of the Tolerance 

Reassessment and Reregistration 

Eligibility Process for the 

Organophosphate Pesticides’’ (July 31, 

2006). 

15. Office of Pesticide Programs, U.S. 

EPA, ‘‘Data Evaluation Report: 

Dichlorvos: A Single Blind, Placebo 

Controlled, Randomized Study to 

Investigate the Effects of Multiple Oral 

Dosing on Erythrocyte Cholinesterase 

Inhibition in Healthy Male Volunteers’’

(March 24, 1998). 

16. Office of Prevention, Pesticides 

and Toxic Substances, EPA, 

Memorandum from Ray Kent/William 

Dykstra to Tina Levine, ‘‘Human Studies 

Review Board: Final Weight of Evidence 

Comparison of Human and Animal 

Toxicology Studies and Endpoints for 

DDVP Human Health Risk Assessment 

and Discussion of Interspecies 

Extrapolation in the Organophosphate 

Cumulative Risk Assessment’’ (March 

20, 2006). 

17. Sass, J., Natural Resources Defense 

Council, ‘‘NRDC comments for the 

HSRB meeting April 4-6, 2006’’

(undated). 

18. EPA Human Studies Review 

Board, Minutes of the United States 

Environmental Protection Agency (EPA) 

Human Studies Review Board (HSRB) 

April 4-6, 2006 Public Meeting Docket 

Number: EPA–HQ–ORD–2006–0187 

(May 15, 2006). 

19. EPA Human Studies Review 

Board, Letter from Celia Fisher to 

George Gray, April 4-6, 2006 Meeting 

EPA Human Studies Review Board 

Report — Proposed Final Draft V. 1 

(May 16, 2006). 

20. EPA Human Studies Review 

Board, Minutes of the United States 

Environmental Protection Agency (EPA) 

Human Studies Review Board (HSRB) 

June 8, 2006 Public Teleconference 

Docket Number: EPA–HQ–ORD–2006–

0187 (June 19, 2006). 

21. EPA Human Studies Review 

Board, Letter from Celia Fisher to 

George Gray, April 4-6, 2006 Meeting 

EPA Human Studies Review Board 

Report (June 26, 2006). 

22. Amvac Chemical Corporation, 

Comments of Amvac Chemical 

Corporation in Reponse to EPA’s Notice 

of a Petition to Revoke Tolerances 

Established for Dichlorvos (November 

13, 2006). 

23. Natural Resources Defense 

Council, Letter submitting comments 

Re: Dichlorvos Interim Reregistration 

Eligibility Decision, 71 FR 37568 (June 

30, 2006) (August 28, 2006). 

24. Reference Dose/Reference 

Concentration (RfD/RfC) Technical 

Panel, Risk Assessment Forum, U.S. 

EPA, ‘‘A Review of the Reference Dose 

and Reference Concentration Processes’’

(December 2002). 

25. USDA, ‘‘Food and Nutrient 

Intakes by Children 1994-96, 1998, 

Table Set 17’’ (December 1999). 

26. USDA, ‘‘Documentation: 

Supplemental Children’s Survey (CSFII 

1998) to the 1994-96 Continuing Survey 

of Food Intakes by Individuals’’ (2000). 

27. Office of Prevention, Pesticides 

and Toxic Substances, EPA, 

Memorandum from Susan V. Hummel 

to Kimberly Lowe/Robert McNally, 

‘‘Revised Preliminary HED Risk 

Assessment for Dichlorvos’’ (August 9, 

2000). 

28. U.S. EPA, Letter from George T. 

LaRocca, Product Manager (13), 

Insecticide Branch, Registration 

Division, to Jon C. Wood, ‘‘Amvac 

Chemical Corp., Dichlorvos (DDVP) 

Label Amendments’’ (October 11, 2006). 

29. Petitioners’ Brief, NRDC v. EPA, 

(2nd Cir. 06-0820-ag) (October 4, 2006). 

30. Natural Resources Defense 

Council, ‘‘Protections for Subjects in 

Human Research; Proposed Rule, 70 FR 

53838’’ (Sept. 12, 2005) (December 12, 

2005). 

31. Respondent’s Brief, NRDC v. EPA, 

(2nd Cir. 06-0820-ag) (November 16, 

2006). 

32. Federal Judicial Center, 

‘‘Reference Manual on Scientific 

Evidence’’ (2d ed. 2000). 

33. Sass, J.B., Needleman, H.L., 

‘‘Industry Testing of Toxic Pesticides on 

Human Subjects Concluded No Effect, 

Despite the Evidence,’’ Environmental 

Health Perspectives. 2004 Mar; 112(3) 

A150-151. 

34. Sass, J.B., Needleman, H.L., 

‘‘Human Testing: Sass and Needleman 

Respond to Industry,’’ Environmental 

Health Perspectives. 2004 Ma; 112(6) 

A340-341. 

35. Lockwood, A.H., ‘‘Human Testing 

of Pesticides: Ethical and Scientific 

Considerations,’’ American Journal of 

Public Health 2004 Nov; 94(11) 1908- 

1916. 

36. Lockwood, A.H., ‘‘The Ethical Bar 

Drops to Unacceptable,’’ Environmental 

Forum. 2005 Nov/Dec; 48. 

37. U.S. EPA, Tolerance Reassessment 

(March 6, 2008) (published at http:// 

www.epa.gov/pesticides/tolerance/ 

reassessment.htm). 

38. Baetcke, K.P., Phang, W., and 

Dellarco, V., Health Effects Division, 

Office of Pesticide Programs, U.S. EPA, 

‘‘A Comparison of the Results of Studies 

on Pesticides from 12- or 24-Month Dog 

Studies with Dog Studies of Shorter 

Duration’’ (April 7, 2005). 

39. U.S. Food and Drug 

Administration, ‘‘Toxicological 

Principles for the Safety Assessment of 

Food Ingredients: Redbook 2000,’’ secs. 

IV.C.4b and IV.C.5. (November 2003). 

40. OECD, ‘‘OECD Guideline For The 

Testing Of Chemicals: Repeated Dose 

90–day Oral Toxicity Study in NonRodents — 409’’ (September 1998). 

41. OECD, ‘‘OECD Guideline For The 

Testing Of Chemicals: Chronic Toxicity 

Studies — 452’’ (May 1981). 

42. OECD Test Guideline No. 452, 

‘‘Chronic Toxicity Studies’’ dated May 

12, 1981; (CPR 52(a)(iii), 52(b)(ii), 

52(c)(ii), 59(a)(iii), 59(b)(ii), 59(c)(ii) and 

63) (Can). 

43. Council Directive No. 2001/59/EC, 

O.J. L 225 (2001) (Annex V of Dir 67/ 

548/EEC on the Classification, 

Packaging and Labeling of Dangerous 

Substances (http://ecb.jrc.it/testingmethods/annex5)). 

44. William Rodgers, Environmental 

Law: Pesticides and Toxic Substances 

(1988). 

X. Regulatory Assessment 

Requirements 

As indicated previously, this action 

announces the Agency’s final order 

regarding objections filed under section 

408 of FFDCA. As such, this action is an 

adjudication and not a rule. The 

regulatory assessment requirements 

imposed on rulemaking do not, 

therefore, apply to this action. 

XI. Submission to Congress and the 

Comptroller General 

The Congressional Review Act, (5 

U.S.C. 801 et seq.), as added by the 

Small Business Regulatory Enforcement 

Fairness Act of 1996, does not apply 

because this action is not a rule for 

purposes of 5 U.S.C. 804(3). 


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Appendix 1—United States 

Environmental Protection Agency 

Human Studies Review Board 

Chair 

Celia B. Fisher, Ph.D. Marie Ward Doty 

Professor of Psychology, Director, Center 

for Ethics Education, Fordham University, 

Department of Psychology, Bronx, NY 

Vice Chair 

William S. Brimijoin, Ph.D., Chair and 

Professor, Molecular Pharmacology and 

Experimental Therapeutics, Mayo 

Foundation, Rochester, MN 

Members 

David C. Bellinger, Ph.D., Professor of 

Neurology, Harvard Medical School 

Professor in the Department of 

Environmental Health, Harvard School of 

Public Health Children’s Hospital, Boston, 

MA 

Alicia Carriquiry, Ph.D., Professor, 

Department of Statistics, Iowa State 

University Snedecor Hall, Ames, IA 

Gary L. Chadwick, PharmD, MPH, CIP, 

Associate Provost, Director, Office for 

Human Subjects Protection, University of 

Rochester, Rochester, NY 

Janice Chambers, Ph.D., D.A.B.T., William L. 

Giles Distinguished Professor, Director, 

Center for Environmental Health Sciences, 

College of Veterinary Medicine, 

Mississippi State University, Wise Center, 

Mississippi State, MS 

Richard Fenske, Ph.D., MPH, Professor, 

Department of Environmental and 

Occupational Health Sciences, University 

of Washington, Seattle, WA 

Susan S. Fish, PharmD, MPH, Professor, 

Biostatistics and Epidemiology, Boston 

University School of Public Health, CoDirector, MA in Clinical Investigation 

Boston University School of Medicine, 

Boston, MA 

Suzanne C. Fitzpatrick, Ph.D., DABT, Senior 

Science Policy Analyst, Office of the 

Commissioner, Office of Science and 

Health Coordination, U.S. Food and Drug 

Administration, Rockville, MD 

Kannan Krishnan, Ph.D., Professor, 

De ́partement de sante ́ environnementale et 

sante ́ au travail, Faculte ́ de medicine, 

Universite ́ de Montre ́al, Montre ́al, Canada 

KyungMann Kim, Ph.D., CCRP, Professor and 

Associate Chair, Department of 

Biostatistics and Medical Informatics, 

School of Medicine and Public Health, 

University of Wisconsin-Madison, 

Madison, WI 

Michael D. Lebowitz, Ph.D., FCCP, Professor 

of Public Health and Medicine. University 

of Arizona, Tucson, AZ 

Lois D. Lehman-Mckeeman, Ph.D., 

Distinguished Research Fellow, Discovery 

Toxicology, Bristol-Myers Squibb 

Company, Princeton, NJ 

Jerry A. Menikoff, M.D., Associate Professor 

of Law, Ethics and Medicine, Director of 

the Institute for Bioethics, Law and Public 

Policy, University of Kansas Medical 

Center, Kansas City, KS 

Robert Nelson, M.D., Ph.D., Associate 

Professor of Anesthesiology and Critical 

Care, Department of Anesthesiology and 

Critical Care, University of Pennsylvania 

School of Medicine, The Children’s 

Hospital of Philadelphia, Philadelphia, PA 

Sean M. Philpott, Ph.D., Research Scientist, 

David Axelrod Institute, Wadsworth Center 

for Laboratories and Research, New York 

State Department of Health, Albany, NY 

List of Subjects in 40 CFR Part 180 

Environmental protection, 

Administrative practice and procedure, 

Agricultural commodities, Pesticides 

and pests, Reporting and recordkeeping 

requirements. 

Dated: July 11, 2008. 

Debra Edwards, 

Director, Office of Pesticide Programs. 

[FR Doc. E8–16617 Filed 7–22–08; 8:45 am] 

BILLING CODE 6560–50–S 

ENVIRONMENTAL PROTECTION 

AGENCY 

40 CFR Part 180 

[EPA–HQ–OPP–2008–0302; FRL–8369–5] 

Fludioxonil; Pesticide Tolerance for 

Emergency Exemption 

AGENCY: Environmental Protection 

Agency (EPA). 

ACTION: Final rule. 

SUMMARY: This regulation establishes a 

time-limited tolerance for residues of 

fludioxonil in or on carambola 

(starfruit). This action is in response to 

EPA’s granting of an emergency 

exemption under section 18 of the 

Federal Insecticide, Fungicide, and 

Rodenticide Act (FIFRA) authorizing 

use of the pesticide on carambola. This 

regulation establishes a maximum 

permissible level for residues of 

fludioxonil in starfruit. The time-limited 

tolerance expires and is revoked on 

December 31, 2010. 

DATES: This regulation is effective July 

23, 2008. Objections and requests for 

hearings must be received on or before 

September 22, 2008, and must be filed 

in accordance with the instructions 

provided in 40 CFR part 178 (see also 

Unit I.C. of the SUPPLEMENTARY

INFORMATION. 

ADDRESSES: EPA has established a 

docket for this action under docket 

identification (ID) number EPA–HQ–

OPP–2008–0302. To access the 

electronic docket, go to http:// 

www.regulations.gov, select ‘‘Advanced 

Search,’’ then ‘‘Docket Search.’’ Insert 

the docket ID number where indicated 

and select the ‘‘Submit’’ button. Follow 

the instructions on the regulations.gov 

website to view the docket index or 

access available documents. All 

documents in the docket are listed in 

the docket index available in 

regulations.gov. Although listed in the 

index, some information is not publicly 

available, e.g., Confidential Business 

Information (CBI) or other information 

whose disclosure is restricted by statute. 

Certain other material, such as 

copyrighted material, is not placed on 

the Internet and will be publicly 

available only in hard copy form. 

Publicly available docket materials are 

available either in the electronic docket 

at http://www.regulations.gov, or, if only 

available in hard copy, at the Office of 

Pesticide Programs (OPP) Regulatory 

Public Docket in Rm. S–4400, One 

Potomac Yard (South Bldg.), 2777 S. 

Crystal Dr., Arlington, VA. The hours of 

operation of this Docket Facility are 

from 8:30 a.m. to 4 p.m., Monday 

through Friday, excluding legal 

holidays. The Docket Facility telephone 

number is (703) 305–5805. 

FOR FURTHER INFORMATION CONTACT: 

Andrea Conrath, Registration Division 

(7505P), Office of Pesticide Programs, 

Environmental Protection Agency, 1200 

Pennsylvania Ave., NW., Washington, 

DC 20460–0001; telephone number: 

(703) 308–9356; e-mail address: 

conrath.andrea@epa.gov. 

SUPPLEMENTARY INFORMATION: 

I. General Information 

A. Does this Action Apply to Me? 

You may be potentially affected by 

this action if you are an agricultural 

producer, food manufacturer, or 

pesticide manufacturer. Potentially 

affected entities may include, but are 

not limited to: 

• Crop production (NAICS code 111). 

• Animal production (NAICS code 

112). 

• Food manufacturing (NAICS code 

311). 

• Pesticide manufacturing (NAICS 

code 32532). 

This listing is not intended to be 

exhaustive, but rather provides a guide 

for readers regarding entities likely to be 

affected by this action. Other types of 


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