§ 158.2230 Toxicology.
(a) General. Subpart B of this part and § 158.2201 describe how to use the table in paragraph (g) of this section to determine the toxicology data requirements for an antimicrobial pesticide product. Notes that apply to an individual test, including specific conditions, qualifications, or exceptions are listed in paragraph (h) of this section.
(b) Uses. The applicant for registration must first determine whether the use is likely to result in pesticide residues in food or water and therefore consult the “Food Use” columns of the table in paragraph (g) of this section. Generally, if the residues of the antimicrobial result from an application to a surface or if incorporated into a material that may come into contact with food or feed, and residues may be expected to transfer to such food or feed, then the “Indirect Food Uses” columns is to be consulted.
(c) Tiering of data requirements. Applicants for registration of antimicrobials may perform tests in a tiered fashion. After the initially required tests are conducted, additional testing may be required if results of the initial tests trigger the need for additional data. Conditions that trigger the need for additional data are given in the test notes in paragraph (h) of this section.
(d) 200 parts per billion (ppb). The 200 ppb level was originally used by the Food and Drug Administration with respect to the concentration of residues in or on food for tiering of data requirements for indirect food use biocides. The Agency has also adopted this same residue level for determining toxicology data requirements for indirect food uses of antimicrobial pesticides. The 200 ppb level is the concentration of antimicrobial residues in the total estimated daily dietary intake.
(e) Use of OSHA standards. If EPA determines that industrial standards, such as the workplace standards set by the Occupational Safety and Health Administration (OSHA standards), provide adequate protection for a particular pesticide or a particular use pattern, additional toxicity data may not be required for that pesticide or the use pattern.
(f) Key. R = Required; CR = Conditionally required; NR = Not required; MP = Manufacturing-use product; EP = End-use product; TGAI = Technical grade of the active ingredient; TEP = Typical end-use product; PAI = Pure active ingredient; PAIRA = Pure active ingredient, radiolabeled; Choice = choice of several test substances depending on studies required.
(g) Antimicrobial toxicology data requirements table. The following table shows the data requirements for toxicology. The test notes applicable to the data requirements in this table appear in paragraph (h) of this section.
Table—Antimicrobial Toxicology Data Requirements
Guideline No. | Data requirement | Food uses | Nonfood uses | Test substance | Test note No. | ||||
---|---|---|---|---|---|---|---|---|---|
Direct food uses | Indirect food uses (>200 ppb) | Indirect food uses (≤200 ppb) | Swimming pools, aquatic areas, wood preservatives, metal working fluids | All other nonfood uses | MP | EP | |||
Acute Testing | |||||||||
870.1100 | Acute oral toxicity—rat | R | R | R | R | R | MP and TGAI | EP and TGAI | 1, 2 |
870.1200 | Acute dermal toxicity | R | R | R | R | R | MP and TGAI | EP and TGAI | 1, 2, 3 |
870.1300 | Acute inhalation toxicity—rat | R | R | R | R | R | MP and TGAI | EP and TGAI | 2, 4 |
870.2400 | Primary eye irritation—rabbit | R | R | R | R | R | MP and TGAI | EP and TGAI | 1, 2, 3 |
870.2500 | Primary dermal irritation | R | R | R | R | R | MP and TGAI | EP and TGAI | 1, 2, 3 |
870.2600 | Dermal sensitization | R | R | R | R | R | MP and TGAI | EP and TGAI | 1, 2, 3, 5 |
870.2600 | Acute neurotoxicity—rat | R | R | CR | R | CR | TGAI | TGAI | 6, 11 |
Subchronic Testing | |||||||||
870.3100 | 90-Day oral toxicity—rodent | R | R | R | R | CR | TGAI | TGAI | 8, 9, 15, 38 |
870.3150 | 90-Day oral toxicity—nonrodent | R | R | CR | R | CR | TGAI | TGAI | 10, 15 |
870.3200 | 21/28-Day dermal toxicity | CR | CR | CR | CR | CR | TGAI | EP and TGAI | 12, 13 |
870.3250 | 90-Day dermal toxicity | CR | CR | CR | CR | CR | TGAI | EP and TGAI | 7, 13, 14, 15 |
870.3465 | 90-Day inhalation toxicity—rat | CR | CR | CR | CR | CR | TGAI | TGAI | 7, 15, 16, 17 |
870.6200 | 90-Day neurotoxicity—rat | R | R | CR | R | CR | TGAI | TGAI | 6, 8 |
Chronic Testing | |||||||||
870.4100 | Chronic oral toxicity—rodent | R | R | CR | R | CR | TGAI | TGAI | 18, 19, 20 |
870.4200 | Carcinogenicity—two rodent species—rat and mouse preferred | R | R | CR | R | CR | TGAI | TGAI | 19, 21, 22 |
Developmental Toxicity and Reproduction | |||||||||
870.3700 | Prenatal developmental toxicity—rat and rabbit preferred | R | R | R | R | R | TGAI | TGAI | 23, 24, 25, 26 |
870.3800 | Reproduction and fertility effects | R | R | R | R | R | TGAI | TGAI | 26, 27, 28, 29 |
870.6300 | Developmental neurotoxicity | CR | CR | CR | CR | CR | TGAI | TGAI | 28, 29, 30 |
Mutagenicity | |||||||||
870.5100 | Reverse mutation assay | R | R | R | R | R | TGAI | TGAI | 31, 32 |
870.5300 870.5375 | In vitro mammalian gene mutation | R | R | R | R | R | TGAI | TGAI | 31, 33 |
870.5385 870.5395 | In vivo cytogenetics | R | R | R | R | R | TGAI | TGAI | 31, 34 |
Special Testing | |||||||||
870.7485 | Metabolism and pharmacokinetics | R | R | CR | R | CR | PAI or PAIRA | PAI or PAIRA | 35, 39 |
870.7200 | Companion animal safety | CR | CR | CR | CR | CR | NR | Choice | 36 |
870.7600 | Dermal penetration | CR | CR | CR | CR | CR | Choice | Choice | 3, 37 |
870.7800 | Immunotoxicity | R | R | R | R | R | TGAI | TGAI | 8 |