Code of Federal Regulations (alpha)

CFR /  Title 40  /  Part 158  /  Sec. 158.34 Flagging of studies for potential adverse effects.

(a) Any applicant who submits a study of a type listed in paragraph (b) of this section must submit with the study a statement in accordance with paragraph (c) of this section.

(b) The following table indicates the 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 paragraph (c) of this section when any criterion is met or exceeded.

Table--Flagging Criteria----------------------------------------------------------------------------------------------------------------

Criteria: Treated animals show Criteria

Study Type(s) Guideline No. any of the following: No.----------------------------------------------------------------------------------------------------------------Carcinogenicity or combined carcinogenicity/ 870.4200 An incidence of neoplasms in 1

chronic feeding study 870.4300 males or females which increases

with dose (positive trend

p<=0.05); or

A statistically significant 2

(pairwise p<=0.05) increase of

any type of neoplasm in any test

group, males or females at any

dose level, compared to

concurrent control animals of

the same sex; or

An increase in any type of 3

uncommon or rare neoplasms in

any test group, males or females

animals at any dose level,

compared to concurrent controls

of the same sex; or

A decrease in the time to 4

development of any type of

neoplasms in any test group,

males or females at any dose

level, compared to concurrent

controls of the same sex.----------------------------------------------------------------------------------------------------------------Prenatal developmental toxicity 870.3700 When compared to concurrent 5Reproduction and fertility..................... 870.3800 controls, treated offspring showDevelopmental neurotoxicity.................... 870.6300 a dose-related increase in

malformations, pre- or post-

natal deaths, or persistent

functional or behavioral changes

on a litter basis in the absence

of significant maternal toxicity

at the same dose level.----------------------------------------------------------------------------------------------------------------Neurotoxicity 870.6100 When compared to concurrent 6

870.6200 controls, treated animals show a

statistically or biologically

significant increase in

neuropathological lesions or

persistent functional or

behavioral changes.----------------------------------------------------------------------------------------------------------------Chronic feeding 870.4100 The no observed adverse effect 7Carcinogenicity................................ 870.4200 level (NOAEL) from one of theseReproduction and fertility..................... 870.3800 studies is less than the NOAELPrenatal developmental toxicity................ 870.3700 currently used by the Agency asDevelopmental neurotoxicity.................... 870.6300 the basis for either the acuteAcute or 90-day neurotoxicity.................. 870.6200 or chronic reference dose.----------------------------------------------------------------------------------------------------------------

(c) Identification of studies. For each study of a type identified in paragraph (b) of this section, the applicant 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) Study does not meet or exceed criteria.

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) Study meets or exceeds criteria.

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].