Guidelines for Safety Evaluation of Microbial
Pesticides
NOTICE TO USERS:All of the translation provided in this document are unofficial. Only theoriginal Japanese texts of the notification are official, and thetranslation is to be used solely as reference materials to aid in theunderstanding of the Japanese notification. FAMIC is not responsible forthe accuracy, reliability or currency of the translation provided in thisdocument, or for any consequence resulting from use of theinformation in this document.

(The notification No. 9-Seisan-5090, issued on August 29, 1997 byDirector-General,

Agricultural Production Bureau, Ministry of Agriculture, Forestry and Fisheries)

Standards for safety evaluation of microbial pesticides
The present standards introduce basic approaches for safety evaluation of microbial
pesticides, and specify date which shall be submitted by a registration applicant for safetyevaluation.
1. Basic approaches for safety evaluation(1) In the present standards, "microbial pesticides" shall mean pesticides containing virus,bacterium, fungus, protozoan or nematode (limited to those containing like as thesymbiotic bacterium as active ingredient) in a viable state which are manufactured orimported for sale for pesticidal purpose. Microbe-derived pesticides which are naturalenemies to parasitic bees, predatory insects, etc. and antibiotics do not come under thecategory of microbial pesticides.
Genetically modified microbes are not included in it either for the moment.
(2) Safety in humans and effects on the organisms etc. in the environment, the safety shallbe demonstrated or confirmed on the basis of scientific data shown in paragraph 2below.
(3) Toxicological studies for safety evaluation shall be performed in compliance with theGLP standard notified by "Notification concerning standards for proper toxicologicalstudies on Agricultural Chemicals (Notification 59 Nohsan No. 3850 * dated August10, 1984), of Director-General of Agricultural Production Bureau, Ministry ofAgriculture, Forestry and Fisheries)."(4) If, as a result of after evaluation based on the data submitted, it becomes necessary toprove or confirm the safety from the standpoint of biological properties of the microbe
and method of using the microbial pesticide, the applicant shall be required to submit
additional data.
2. Data serving as the basis for safety evaluation(1) Data necessary for safety evaluation of microbial pesticides are stipulated for in theAttached List "Data required, by type of microbe, for safety evaluation of microbial
pesticides."(2) When the data for safety evaluation have already been submitted for the registration
application of other microbial pesticides formulation, the said data can be used for theregistration application of new formulation. In addition, when one applicant agrees
that other applicant uses the said data, which have already been submitted forregistration, new applicant is required to submit a certificate indicating that the said
data is allowed to use by a former applicant.

（*）the notification was replaced to the Notification No. 11-Nousan-6283, issued on October
1,1999.
-1-

Attached List
Data required, by type of microbe, for safety evaluation of microbial pesticides
Data required

Type of microbe
VirusOthers(1) Name and taxonomic position ofmicrobe○○(2) Biological properties of microbe○○(3) Composition of technical grade of
the active ingredient○○(4) Production method for technicalgrade of the active ingredient○○(5) Composition of end-use product○○(6) Production method for end-use
product○○(1) Diseases, pests and weeds forwhich the microbial pesticide is to
be used, and crop plants to which
the microbial pesticide is to beapplied○○(2) Method of use and use level○○(1) Acute oral toxicity/infectivity study○○(2) Acute dermal toxicity/ irritation
study

○

○

(3) Acute pulmonary toxicity/infectivity study○○(4) Acute intravenous
toxicity/infectivity study○○(5)Eye irritation study○○(6) Skin sensitization study○○Remarks

1. Data concerning specification andproperties of microbial pesticides

2. Data concerning method of use

3. Results of studies of safety in humans

Test should be performed where virus, bacterium orfungus is involved.

(7) Cell culture study○

×(8) Repeated dose toxicity /infectivity
study

△

△

This test should be performed if any infectivity or
residual microbial viability has been found in theacute toxicity/infectivity study(9) Mutagenicity study

×▲

If, in the case of fungi, any infectivity has been
observed in the repeated dose toxicity /infectivity
study, this test should be performed.

(10) Reproductive toxicity/infectivity
study

▲

▲

If the repeated dose toxicity /infectivity study hasrevealed any infectivity etc., this test should beperformed.

(11) Viral carcinogenicity study▲▲

If any infectivity etc., has been noted in mammaliananimal cells in the cell culture study, this study
should be performed.

(12) Immunodeficiency inducing study▲

×

If the cell culture study has revealed any infectivity
etc. in mammalian animal cells, this study should beperformed.

(13) Effect test on primates▲

×- ditto –-2-Data required

Type of microbe

Remarks

VirusOthers

4. Data concerning cases ofhypersensitive reactions that occurredin production and use of microbial
pesticides○○

5. Results of studies of residual
microbial viability on crop plants△△

If, in the case of microbial pesticides for food crops,
any effects have been observed in the Tier I ofsafety in humans, excluding primary eye irritationand dermal sensitization studies, this test should beperformed.

(1) Toxicity study on freshwater fish○○

When there is no possibility of exposure, because ofscientific grounds from the viewpoint of biologicalproperties of the microbe or judging from themethod of use, this test may be omitted.

(2) Toxicity study on freshwater
invertebrates○○- ditto -(3) Avian toxicity study○○- ditto -(4) Study of effects on non-target
plants○○- ditto -(5) Study of effects on non-target
insects○○- ditto -(6) Study of effects on honey bees○○- ditto -(7) Study of effects on silkworms○○- ditto -(8) Study of effects on soil microbes○○- ditto -7. Results of studies of fate in theenvironment△△

If any effects have been observed in the effect teston the organisms in the environment, required tests
should be performed.

6. Results of effect test on the organisms
in the environment〇: Required in the Tier I△: Required in the Tier II▲: Required in the Tier III
×: Not required(Note) As regards the Tier I, II or III, if any infectivity etc. have been found in the Tier I in any of the tests,
the test proceeds to the Tier II, and Tier III of test is performed if any infectivity etc. have been
observed in any of the Tier II or if any infectivity etc. have been noted in the Tier I of the cell
culture test. Proceeding of the test stage in studies of safety in humans is shown in Attached Fig. 1,and effect test on the organisms in the environment (Tier I) and studies of fate in the environment(Tier II) are shown in Attached Fig. 2.

-3-Attached Fig. 1
Toxicological studies for safety evaluation
Tier I

Tier II

Tier III
Additional study (Identification oftoxin, and study with the toxic
substance identified)

Presence of toxicity

Repeated dose toxicity/infectivity study (90 days)

Acute toxicity/infectivity study(14 days or 21 days)
Acute oral toxicity/infectivity
study
Acute dermal toxicity/ irritation
study
Acute pulmonary
toxicity/infectivity study
Acute intravenous
toxicity/infectivity study

Presence of infectivity or residual
microbial viability

No infectivity,
pathogenicity,
toxicity or residual
microbial viability
Presence of
pathogenicity

Repeated dose oral
toxicity/infectivity study

Repeated dose pulmonary
toxicity /infectivity study
Not necessary toproceed to the nextstage of test

Carcinogenicity study (Identificationof mutagenic substance, and study
with the mutagenic substancePresence of
toxicity

Mutagenicity study (only fungus)

Presence of infectivity
No infectivity,
pathogenicity ortoxicity

Reproductive toxicity/infectivity
Not necessary toproceed to the nextstage of test

Presence of pathogenicity
Effects study

Presence of
toxicity

Study of step to be taken

Cell culture study

Presence of infectivity(only virus)
No infectivity,toxicity or phenotypictransformation

Eye irritation study
Skin sensitization study(where virus, bacterium orfungus is involved)

on primates

Not necessary toproceed to the nextstage of test

Viral carcinogenicity study

Immunodeficiency inducing study(only virus)

Positive

Attached Fig. 2
Ecotoxicology study and Environmental fate study

Tier I

Tier III

Tier II

Ecotoxicology study
1. Toxicity study on freshwater fish
2. Toxicity study on freshwater
invertebrates

Possibility of exposure
Presence of effects

3. Avian toxicity study

Studies of fate in theenvironment

Study of step to betaken

No possibility of exposure
Not necessary toproceed to the nextstage of test

4. Study of effects on non-target
plants
5. Study of effects on non-target
insects
6. Study of effects on honey bees
7. Study of effects on silkworms

No effects

Not necessary toproceed to the nextstage of test

8. Study of effects on soil microbes(Note) Where there is no possibility of exposure, because of scientific grounds from the viewpoint of biological properties of the microbe or judging from the method of use, test may be omitted.