§ 158.2140 - Microbial pesticides toxicology data requirements table.

§ 158.2140 Microbial pesticides toxicology data requirements table.

(a) General. Sections 158.100 through 158.130 describe how to use this table to determine the toxicology data requirements for a particular pesticide product. Notes that apply to an individual test and include specific conditions, qualifications, or exceptions to the designated test are listed in paragraph (d) of this section.

(b) Key. R = Required; CR = Conditionally required; NR = Not required; MP = Manufacturing-use product; EP = End-use product; TEP = Typical end-use product; TGAI = Technical grade of the active ingredient; All = All of the above. Specific conditions, qualifications, or exceptions to the designated test procedures appear in paragraph (d) of this section, and apply to the individual tests in the following table:

(c) Table. The following table shows the data requirements for microbial pesticides toxicology. The test notes are shown in paragraph (d) of this section.

Table - Microbial Pesticides Toxicology Data Requirements

Guideline Number	Data Requirement	All Use Patterns	Test Substance	Test Notes
Tier I
885.3050	Acute oral toxicity/pathogenicity	R	TGAI	1
885.3150	Acute pulmonary toxicity/pathogenicity	R	TGAI	- -
885.3200	Acute injection toxicity/pathogenicity/(intravenous) Acute injection toxicity/pathogenicity/(intraperitoneal)	R	TGAI	2
885.3400	Hypersensitivity incidents	R	All	3
885.3500	Cell culture	R	TGAI	4
870.1100	Acute oral toxicity	R	MP , EP	1, 5
870.1200	Acute dermal toxicity	R	MP , EP	5
870.1300	Acute inhalation toxicity	R	MP , EP	5, 6
870.2400	Acute eye irritation	R	MP , EP	5
870.2500	Primary dermal irritation	R	MP , EP	5
Tier II
885.3550	Acute toxicology	CR	TGAI	7
885.3600	Subchronic toxicity/pathogenicity	CR	TGAI	8
Tier III
885.3650	Reproductive fertility effects	CR	TGAI	9, 13
870.4200	Carcinogenicity	CR	TGAI	10, 13
870.7800	Immunotoxicity	CR	TGAI	11, 13
885.3000	Infectivity/pathogenicity analysis	CR	TGAI	12, 13

(d) Test notes. The following test notes are applicable to the data requirements for microbial pesticides toxicology as referenced in the last column of the table contained in paragraph (c) of this section:

1. The acute oral toxicity/pathogenicity study is required to support the TGAI. However, it can be combined with the unit dose portion of the acute oral toxicity study, with an EP or MP test material to fulfill the requirement for the TGAI and the MP or EP in a single study, if the new protocol is designed to address the endpoints of concern.

2. Data not required for products whose active ingredient is a virus. For test materials whose size or consistency may prevent use of an intravenous injection, the intraperitoneal injection procedure may be employed.

3. Hypersensitivity incidents, including immediate type and delayed-type reactions of humans or domestic animals, occur during the testing or production of the TGAI, MP, or EP, or are otherwise known to the applicant must be reported if they occur.

4. Data must be submitted only for products whose active ingredient is a virus.

5. The 870 series studies for the MP and EP are intended to provide data on the acute toxicity of the product. Waivers for any or all of these studies may be granted when the applicant can demonstrate that the combination of inert ingredients is not likely to pose any significant human health risks. Where appropriate, the limit dose approach to testing is recommended.

6. Required when the product consists of, or under conditions of use would result in, an inhalable material (e.g., gas, volatile substances, or aerosol particulate).

7. Data required when significant toxicity, in the absence of pathogenicity and significant infectivity, is observed in acute oral, injection, or pulmonary studies (Tier I). Route(s) of exposure correspond to route(s) where toxicity was observed in Tier I studies. The toxic component of the TGAI is to be tested.

8. Data required when significant infectivity and/or unusual persistence is observed in the absence of pathogenicity or toxicity in Tier I studies. Routes of exposure (oral and/or pulmonary) correspond to routes in Tier I studies where adverse effects were noted. Data may also be required to evaluate adverse effects due to microbial contaminants or to toxic byproducts.

9. Data are required when one or more of the following criteria are met:

i. Significant infectivity of the microbial pest control agent (MPCA) was observed in test animals in the Tier II subchronic study and in which no significant signs of toxicity or pathogenicity were observed.

ii. The microbial pesticide is a virus which can persist or replicate in mammalian cell culture lines.

iii. The microbial pesticide is not amenable to thorough taxonomic classification, and is related to organisms known to be parasitic for mammalian cells.

iv. The microbial pesticide preparation is not well purified, and may contain contaminants which are parasitic for mammals.

10. Data may be required for products known to contain or suspected to contain carcinogenic viruses or for microbial components that are identified as having significant toxicity in Tier II testing.

11. Data may be required for products known to contain or suspected to contain viruses that can interact in an adverse manner with components of the mammalian immune system.

12. An analysis of human infectivity/pathogenicity potential using scientific literature, genomic analysis, and/or actual specific cell culture/animal data may be required for products known to contain or suspected of containing intracellular parasites of mammalian cells for products that exhibit pathogenic characteristics in Tier I and/or Tier II, for products which are closely related to known human pathogens based on the product analysis data, or for known human pathogens that have been “disarmed” or rendered non-pathogenic for humans.

13. Test standards may have to be modified depending on the characteristics of the microorganism. Requirements may vary for these studies depending on the active ingredient being tested. Consultation with the Agency is advised before performing these Tier III studies.