§158.34 Flagging of studies for potential adverse effects.

(a) Any person who submits a study of a type listed in paragraph (b) of this section to support an application for new or amended registration, or to satisfy a requirement imposed under FIFRA sec. 3(c)(2)(B), must submit with the study a statement in accordance with paragraph (c) of this section.

(b) The following table indicates that study types and the criteria to be applied to each. Column 1 lists the study types by name. Column 2 lists the associated Pesticide Assessment Guideline number. Column 3 lists the criteria applicable to each type of study. Column 4 lists the reporting code to be included in the statement specified in §158.34(c) when any criterion is met or exceeded.

                                             Table_Flagging Criteria
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                                            Pesticide
                                            assessment                                                Reporting
             Toxicity studies               guidelines                    Criteria                       code
                                               No.
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Oncogenicity [or combined oncogenicity/           83-2  Treated animals show any of the following:   ...........
 chronic feeding study]
 or
Subchronic feeding study.................         82-1  An incidence of neoplasms in male or female            1
                                                         animals which increases with dose;
                                           ...........   or
                                           ...........  A statistically significant (p [lE]0.05)               2
                                                         incidence of any type of neoplasm in any
                                                         test group (male or female animals at any
                                                         dose level) compared to concurrent control
                                                         animals of the same sex;
                                           ...........   or
                                           ...........  An increase in any type of uncommon or rare            3
                                                         neoplasms in any test group (male or
                                                         female animals at any dose level) compared
                                                         to concurrent control animals
                                           ...........   or
                                           ...........  A decrease in the time to development of               4
                                                         any type of neoplasms in any test group
                                                         (male or female animals at any dose level)
                                                         compared to concurrent control animals
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Teratogenicity...........................         83-3  When compared with concurrent controls,                5
                                                         treated animals show a dose-related
                                                         increase in malformations (or deaths) on a
                                                         litter basis in the absence of significant
                                                         maternal toxicity at the same dose levels
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Neurotoxicity............................         81-7  When compared with controls, treated                   6
                                                         animals show a response indicative of
                                                         acute delayed neurotoxicity
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Chronic feeding study or combined chronic         83-1  Cholinesterase inhibition NOEL less than 10            7
 feeding/oncogenicity study                              times the current existing ADI.
                                           ...........   or
                                           ...........  General (systemic) toxicity NOEL less than             8
                                                         100 times the current existing ADI.
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Reproduction study.......................         83-4  Reproductive effects NOEL less than 100                9
                                                         times the current ADI.
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Subchronic feeding study.................         82-1  Cholinesterase inhibition NOEL less than              10
                                                         100 times the current existing ADI.
                                           ...........   or
                                           ...........  General (systemic) toxicity NOEL less than            11
                                                         1000 times the current existing ADI.
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(c) Identification of studies. For each study of a type identified in paragraph (b) of this section, the applicant (or registrant in the case of information submitted under FIFRA sec. 3(c)(2)(B)) shall include the appropriate one of the following two statements, together with the signature of the authorized representative of the company, and the date of signature:

(1) "I have applied the criteria of 40 CFR 158.34 for flagging studies for potential adverse effects to the results of the attached study. This study neither meets nor exceeds any of the applicable criteria."

(2) "I have applied the criteria of 40 CFR 158.34 for flagging studies for potential adverse effects to the results of the attached study. This study meets or exceeds the criteria numbered [insert all applicable reporting codes.]"

[53 FR 15992, May 4, 1988, as amended at 58 FR 34203, June 23, 1993]