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Biochemical pest control agents include four (4) general biologically functional
classes, which are described below:
A. Semiochemicals
These biorational pesticides include (but are not limited to) bacteria, fungi,
viruses, and protozoans. The guidelines apply to all microbial pest control
agents used as pesticides, including not only those that are naturally occurring,
but also the improved strains.
3.2.2
Approach to
Testing
To meet the intent of the above policy, the following elements comprise
the approach taken by FPA: exposure criteria (for biochemicals), maximum
hazard testing, and a tier testing scheme.
A. Exposure Criteria
There are certain factors often associated with biochemical pest
control agents or their use that significantly limit the agents potential for
human and other non-target organism exposure and, therefore,
hazardous. Any or all of these factors provide the basis for reduced
data requirements. These factors are: low exposure from pesticide
formulation, low rate of application, non-aquatic use site, and high
volatility.
C. Tier Testing
Scheme
The tier testing scheme is used to ensure that only the minimum
data necessary to make a scientifically sound regulatory decision are
generated. This scheme eliminates the need for submission of
extensive data for those pesticides that are determined to be safe on the
basis of Tier I data. It is expected that many biorational pesticides
would require only Tier I testing. The Tier Testing Scheme is discussed
in detail in Section 4.
3.3 PRODUCT SPECIFICATION DATA
The product analysis data for biorational pesticides closely parallel those
for conventional chemical pesticides as specified in Table 2.. However,
important differences exist due to the unique nature and mode of action of
biorationals as noted below.
For this group, the data requirements parallel those required for
conventional chemical pesticides in terms of the detailed information on the
procedures by which the active ingredient is produced, and the techniques used
to ensure a uniform or standardized product. If the standardization techniques
include methods of bioassay, then these methods shall be described.
Particular interest is given to the ingredients, which may be toxic or sensitizing to
humans or other non-target species. The following are the product analysis
guidelines for this group:
A. Product
Identity
C. Information on Ingredients
c. The chemical name for the Chemical Abstracts or other well-defined name;
e. The product name, the trade name, and the common name (if established);
g. For each active ingredient other than the biochemical, the empirical formula, and the
molecular weight or the molecular weight range; and
b. The steps taken, both chemical and biological, to ensure the integrity of the starting
material and to limit the extraneous contamination in the unformulated biochemical shall
be given;
c. The procedures by which the manufacturer established the identity and purity of the
seed stock from which the unformulated biochemical is produced shall be described; and
d. The quality control methods and the techniques used to ensure a uniform or
standardized product shall be reported. Unless the quality control methods are well
established and recognized, they shall be submitted in detail with information regarding
their accuracy, sensitivity, and the interfering substances.
F. Analysis of
Samples
For this group, due to the unique nature, composition, and mode of action
of microbial agents, data requirements differ in some respects. For example,
bacteria, fungi, protozoa, and viruses shall be identified to the extent possible by
taxonomic position, serotype, composition, and strain, or by any other
appropriate specific means. This information would take the place of chemical
name and structural formula for conventional pesticides. As a result, certain
portions of the data requirements table (Table 6.) do not apply. There must be
assurance, however, that the methods used and the data submitted are capable
of demonstrating that the biorational pesticide used in the field is the same as
that which was tested for safety.
A. Product
Identity
C. Information on Ingredients
a. The taxonomic position, serotype, and strain, or any other appropriate designation.
The precise test procedures and criteria used for identification (i.e., the morphological,
biochemical, analytical (physical, chemical), serological, or other identification means)
and the results of such tests should be provided;
c. The natural occurrence of the organism, its relationship to other species (particularly
those that are pathogenic), and its history; and
c. The chemical name from the Chemical Abstracts 1972-1976 Index of Nomenclature, or
other well-defined name;
d. The Chemical Abstract (CAS) Registry Number;
e. The product name, the trade name, and the common name (if established);
g. For each active ingredient other than the microbial agents, the empirical formula, and
the molecular weight or the molecular weight range;
i. The composition limits for each ingredient for which limits are required to be certified.
This may be included in the confidential statement of formula;
j. The amount of microbial agent present in the product in recognized units of potency,
percentage of weight, units of viability or replication, or other appropriate expression of
biological activity; and
k. The biological properties of the active agent with respect to target species, pest host
range, life cycle, and mode of action. With respect to the properties of the microbial
agent, any potential hazard (such as ineffectivity) to man, the environment, or non-target
species should be discussed.
D. Manufacturing Process
3.4 TOXICOLOGY
3.4.1
Majo
r Concerns
Because the field is new, many problems related to toxicology and hazard
evaluation would undoubtedly be encountered. It is recognized that for some
biorational pesticides, there are no well-recognized and standard test methods
for assessing the toxicological hazards to mammals. When problems arise, the
registrant is urged to discuss the matter with FPA so that alternative methods and
protocols can be considered prior to the actual conduct of the tests.
3.4.2
Biochemica
l Agents
3.4.3
Microbi
al Agents
A. Tier
I Testing
B. Tier
II Testing
Guidelines are contained in the following reference documents:
A. Tier
I Testing
B. Tier
II Testing
A.
Approa
ch
B. Tier
Progression
A. Approach
1. The efficacy of the agent often depends upon its ability to replicate in
the target pest which is not likely to remain on the crop after
harvest;
2. The living form of the agent in most instances will usually not replicate
in the absence of the specific target pest (e.g. insect host);
B. Tier
Progression
Residue data for microbial pest control agents used in food, feed,
or raw agricultural commodities shall only be required if toxic or other
harmful properties were observed in the maximum hazard toxicology tests
(Tier I). If Tier I toxicology tests indicate no toxic or other harmful
properties, then no residue data would be indicated and thus a
recommendation for an exemption from the requirements of a tolerance
can be made.
3.6.1
Biochemica
l Agents
A. Terrestrial
Wildlife
a. Innate toxicity is not inherent to the nature and mode of action of biochemical agents;
b. Experience so far indicates that most of these pesticides will be applied at very low rates
compared to conventional chemical pesticides, thereby reducing likelihood or significant
exposure to non-target organisms; and
c. Past experience likewise indicates that most biochemical pest control agents are not
acutely toxic (e.g. LC50 and LD50 values in Avian species of most biochemical agents
are greater than 5000 ppm or 2000 mg/Kg, respectively).
a. If signs of abnormal behavior are reported in Tier I tests at levels equal to or less than
the maximum expected environmental concentration; or
c. If the maximum expected environmental concentration is equal to or greater than 1/5 the
LC50 values established in Tier I terrestrial wildlife studies, or equal to or greater than
1/10 the LD50 or LC50 values established in Tier I aquatic animal studies.
Maximum application rate
Dose
454**
Maximum application rate
Concentration
454**
**
For example, a 20 gram/acre (49 gram/hectare) rate would give
an 88 mg/Kg maximum test dose and a maximum test
concentration of 220 ppm.
b.Categorization of semiochemicals by
structure /activity relationships. Categorization of
chemicals is a method through which scientists can infer
which chemicals present risks or harm to humans and to
the environment. The study of structure/activity
relationships (SAR) seeks to find association between a
substance physical and chemical properties and its effect
on biological activity. Use of SAR in the assessment of
adverse effects of some industrial chemicals to non-target
organisms, such as shrimp and clams, had been reported
(Mcleese et al, 1979). Since most semiochemicals used
as pesticides are applied at very low rates and possess
special physicochemical properties (such as high volatility)
that lessen their exposure to terrestrial animals, acute
toxicity data on terrestrial animals for each new
semiochemicals submitted for registration may not be
necessary. Rather, a determination of hazard could be
based on existing acute toxicity data for structurally similar
semiochemicals.
B. Aquatic
Animals
C. Non-Target
Plants
D. Non-target
Insects
1. Approach. Development of baseline (first
tier) tests for biochemical pesticides is difficult, for the following
two reasons:
b. Major Issues
2. Aquatic Animals
3. Non-target Plants
4. Non-target Insects
Tier III. For all microbial pest control agents, Tier III consists
of advanced tests specifically responding to adverse effects
identified in earlier tier testing. Such tests may be simulated
or actual field tests. In any case, Tier III testing would be
preceded by consultation with FPA.
B. Tier
Testing
A. Scope and
Definition
Potential adverse effects are seen in Tier I Testing. (If not, no testing is indicated in Tier II
unless product as aquatic use pattern or biochemical is not applied in a controlled release device, in which
case should proceed directly to Persistence Testing.
TRANSPORT TESTING
Volatility (# 155-4)*
*
PERSISTENCE TESTING
Adsorption/desorption (#155-6)*
Hydrolysis (#155-9)
need for Tier III testing whenever the results show that the agent
limiting its direct concern to, and requiring efficacy data for
products having health related use patterns and products
keeping with this concern, the Administrator has deemed that all
in the product development stages, and the Tier I toxicology and non-
public health areas, but the submittal of data on host spectrum, and
A. General Provision
or noted.
Section 3.3
2. Toxicology Data
application:
on food crops:
and
Intravenous, intrecerebral,
intraperitoneal infectivity;
plus
Cellular immune
response; and
viral agents.
C. Residue Data
application; or
2. Tier I toxicology studies conducted under paragraph B.2.ii
following situations:
1. Initial permits. Efficacy data may be
patterns:
organisms; and
making:
3.10.1 Approach
and the environment, the FPA is currently pursuing and promoting the
consequent lower risks of adverse effects from their use must be taken
agents for practical use. One of the more obvious vehicles available
AGENTS)
Technical/
2.0 SPECIFICATIONS
Technical/
3.0 BIOEFFICACY
TIER I
TIER
II
Technical/
Technical/
6.1 Volatility R R R
6.2 Adsorption/Desorption R R R
7.0 LABELLING
is genetically engineered.
Table 6. SUMMARY OF DATA REQUIREMENTS FOR THE
REGISTRATION OF BIORATIONALS (MICROBIAL PEST CONTROL
AGENTS)
Technical/
2.0 SPECIFICATIONS
Table 6. (continued)
Technical/
3.0 BIOEFFICACY
TIER I
Technical/
4.3 Irritation
TIER II3
33 Not all tests may be indicated for each microbial pest control agent, the
appropriate tests will depend on the results of Tier I and/or Tier II tests.
4.1 Subchronic oral (mice, rat or dog; 90 day P
2 test)
4.1 Primary dermal (guinea pig, use dilution P
3 doses)
4.1 Primary occular (rabbit, use dilution BFVP
4 doses)
4.1 Cellular Immune Response (antibody BFVP
5 formation cell mediated response)
4.1 Teratogenicity tests (two species from rat, BFVP
6 mouse, hamster, rabbit)
4.1 Mutagenicity tests (mammalian cell, see BFV
7 text)
4.1 Virulence enhancement (mice or hamster, BFVP
8 serial passage)
TIER III3
Technical/
6.1 Volatility R R R
6.2 Adsorption/Desorption R R R
If pesticide like to reach soil or water
6.3 Leaching R R R
6.4 Degradation in soil R R R
is genetically engineered.
Table 6. (continued)
Technical/
7.0 LABELLING
1.0 GENERAL
2.0 SPECIFICATIONS
3.0 BIOEFFICACY
8.0 LABELLING
Histopathology D X X
Serology* NA D X
Nucleic Acid NA NA D
Hybridization**
**
A typical application rate for conventional pesticides.
*
Number in parenthesis indicate the section series and sub-series number in US EPA Pesticide
**