GUIDELINES ON REGISTRATION OF PESTICIDES

Transcription

1
Pesticides Act 1974
________________________________________________________________
GUIDELINES ON REGISTRATION OF
PESTICIDES
Secretariat
Pesticides Board
Department of Agriculture
Ministry of Agriculture and Agro-Based Industry Malaysia
August 2009
2
PREFACE
The Purpose of these of these guidelines is to provide guidance to all
potential applicants on the legal requirements to register pesticides before
they are allowed to be imported or manufactured for sale and use in the
country as provided for under the Pesticides Act 1974.
These Guidelines replace the ‘Guidelines on Registration and Labelling of
Pesticides’ issued by the Pesticides Board in 1991 (4th Edition). The
present registration guidelines were revised to accommodate the changes
brought about by the amendment to the Pesticides Act 1974 which was
passed by the Parliament in 2004. There are a number of new or
amended provisions in the Act that affects the registration processes and
procedures. These include the requirement for applicants to pay an
application fee and a registration fee as well as the extension of the
registration period from 3 years to 5 years.
These guidelines provide information on the application procedures to
guide the applicants on how submissions for pesticides registration can
be made to the Pesticides Board. It also provide an explanation on the
requirements to register commodity and proprietary pesticides as well as
new registration and re-registration procedures.
It is important to note that, these guidelines should be read together with
other guidelines and related circulars produced by the Pesticides Board,
in particular guidelines on data requirements namely on physical and
chemical properties, toxicology and eco-toxicology, residue, bio-efficacy
and environmental fate.
Pesticides Board
Pesticides Control Division
Department Of Agriculture
Ministry Of Agriculture And Agro-Based Industry Malaysia
August 2009
3
TABLE OF CONTENTS
Preface
………………………………………..
i
Table of Contents
………………………………………..
ii
Introduction
………………………………………..
1
Terms and Definitions
………………………………………..
1
…….……........... 1
Pesticide
Proprietary and commodity pesticide
……………. 1
Manufacture
……………. 2
Registration
……………. 2
Application Procedures
………………………..…………….
How To Apply For Registration
………………….
3
3
New registration
……………. 4
Re-Registration
……………. 5
Guidance On How To Complete The Application Form……… 6
Labelling requirements
………………………………………..
Manufacturing for export purposes
Importation of unregistered pesticides
Penalties
7
…………………………. 7
…………………… 7
……………………………………………….
8
ANNEXES
………………………….. 9
I
Standard Covering Letter
II
Summary Of Data Requirements For Proprietary And
Commodity Pesticides According To General Use Pattern……11
III
Sample label
………………………………………….. 20
4
INTRODUCTION
Sections 7-13 of the Pesticides Act 1974 provides for the control of importation and
manufacture of pesticides. The objective of pesticide registration is aimed at ensuring
that pesticides offered for sale in the country are of good quality, effective for their
intended use and at the same time would not cause unacceptable adverse effects to
man and the environment.
Registration of pesticides is implemented through the Pesticides (Registration) Rules
2005 which was gazetted on 18 August 2005 to replace the Pesticides (Registration)
Rules 1976. These new Rules describe how pesticide registration approval can be
obtained from the Pesticides Board.
TERMS AND DEFINITIONS
Pesticide
The term ‘pesticide’ under the Pesticides Act 1974 is defined as ‘any substance that
contains an active ingredient’ or ‘any preparation, mixture or material that contains any
one or more of the active ingredients as one of its constituents’, while the term ‘active
ingredient’ means an ingredient, as listed in the First Schedule of the Pesticides Act
1974.
Generally pesticides includes, but are not limited to, herbicides, insecticides,
fungicides, acaricides, nematicides, rodenticides, molluscicides, bactericides,
fumigants, soil fumigants, miticides, preservatives, repellants and termiticides.
Applicants are required to refer to the First Schedule of the Pesticides Act 1974, in
order to ascertain whether their product contains any of the listed active ingredients,
thus requiring registration. As the First Schedule is updated from time to time to
include new active ingredients, it is necessary for the applicant to refer to the
Pesticides Board for the updated listing.
Proprietary and Commodity Pesticide
For the purpose of registration, pesticides are divided into 2 categories namely
proprietary and commodity.
Commodity pesticides are pesticides containing active ingredients that have been
registered in Malaysia for not less than 10 years.
Proprietary pesticides are pesticides that are not commodity pesticides as defined
above are classified as proprietary pesticides. In case the of a pesticide mixture
containing proprietary and commodity active ingredients, the pesticide shall be
considered as a proprietary pesticide.
5
Manufacture
The term manufacture as defined by the Act means to prepare, compound, formulate,
mix, make, pack, re-pack or label a pesticide or otherwise treat the pesticide with a
view to its sale.
Registration
Registration is a process of evaluation and approval by the Pesticides Board before a
pesticide is allowed to be imported, manufactured, sold and used in the country. Only
those pesticides that are of good quality, effective for the intended purposes and do
not cause unacceptable adverse effect on human beings, animals, plants, fruits or
property would be registered in the country.
In order for the evaluation to be carried out, the Pesticides Board requires the
applicant to submit relevant data when applying for the registration. The data
requirements for pesticide registration under these rules are adapted from the Food
and Agriculture Organisation of the United Nations (FAO) and other international
organizations. The details of information required for evaluation are given in the
application form.
A separate application is required if the pesticide is different from another pesticide. A
pesticide is considered different from another pesticide, if:
(a) the active ingredient of that pesticide is different from that of the other
pesticide;
(b) the trade name or trade mark of that pesticide is different from that of the
other pesticide;
(c) the ingredients of that pesticide are different from those of the other
pesticide in type, number, proportion, concentration, or in other respects; e.g.
glyphosate isopropylamine 13.6% w/w soluble concentrate (SL) and glyphosate
isopropylamine 41.0% w/w soluble concentrate (SL) must be registered
separately under each concentration;
(d) the pesticide is differently formulated from the other pesticide, e.g. if alpacypermethrin is formulated as an emulsifiable concentrate (EC) and also as
suspension concentrate (SC), it must be registered separately under each
formulation;
(e) the pesticide is manufactured by a manufacturer other than the
manufacturer of the other pesticide; e.g. if benomyl is manufactured by two
companies, the products from both companies must be registered separately
even if the products are identical; or
(f) that pesticide is different in quality, nature, characteristics or efficacy from
the other pesticide; e.g. if one azadirachtin product is different in quality, nature,
6
characteristics or efficacy
separately from the other.
from another product it must be registered
A separate application is also required if the category of usage is different e.g.
insecticide for agriculture use and insecticide for public health.
APPLICATION PROCEDURES
Application For Registration
Application to register and re-register a pesticide must be made using Application
Form, Form A [Subrule 2(1)] (Application For Registration/Re-registration Of A
Pesticide)] and only locally registered companies may apply. All applications must be
submitted to the following address:
Secretary
Pesticides Board
Pesticides Control Division
4th Floor Wisma Tani
Jalan Sultan Salahuddin
50632 Kuala Lumpur.
Tel No: 03-2030 1400
Fax No: 03-2691 7551
Application forms are obtainable from the above-mentioned address. Submissions
should be made well in advance of the desired registration date.
Applicants should indicate in the standard cover-letter of the application (see Annex I)
whether the product is a commodity pesticide or a proprietary pesticide. The onus is
on the applicant to provide evidence that a product is a commodity pesticide. Some
common active ingredients which are considered as commodity pesticides are listed in
the latest edition of “Syor-Syor Kawalan Diluluskan Untuk Racun Perosak Komoditi”
(GP5). This list serves as a guide only and is subject to review from time to time. For
commodity pesticides, some registration requirements have been waived but the
Pesticides Board reserves the right to still request for them if necessary.
Applicants are also advised not to proceed with the printing of the final labels until the
product has been granted registration.
The period of registration of a pesticide is 5 years, effective from the date of
registration unless it is terminated by the registrant or cancelled by the Pesticides
Board. Under the Pesticides (Registration) Rules 2005, two types of fee will be
imposed on an application to register and re-register a pesticide. The fee for an
application is RM1,500.00 (one thousand five hundred ringgit) payable at the time
the application is submitted. This fee is not refundable. Upon approval, a
registration/re-registration fee will be imposed for each product payable prior to the
issuance of the Registration Certificate. The amount1 imposed for registration varies
according to class as follows:-
7
Class 1a and 1b per approval: RM3,500.00 (three thousand five hundred ringgit)
Class II per approval
: RM2,000.00 (two thousand ringgit)
Class III per approval
:RM1,000.00 (one thousand ringgit)
Class IV per approval
: RM 500.00 (five hundred ringgit only)
New Registration
The following are the requirements for an application for registration of a new
pesticide:
a) Five (5) sets of application forms and supporting information.
This must include a set of the original copy. If the information submitted consists of
many volumes, a complete dossier with the original set and four (4) sets of
summaries may be submitted. Please refer Part E of the Application Form for the
information to be submitted.
b) All information must be on A4 size paper, properly filed in A4 size folders and
accompanied by a standard cover-letter. (See Annex I).
c) The source(s) of a pesticide must be declared in the cover letter. In addition a letter
from the source(s) confirming that they are the suppliers of the pesticide should
also be submitted. A maximum of 3 sources will be allowed at any one time
provided the composition and percentage of all the ingredients are identical. An
outline of the manufacturing process from all the sources must be submitted. Any
change of source(s) or manufacturing process during the period of registration
must be approved by the Pesticides Board.
d) Letter authorizing the use of data from the owners of the data.
e) Each set of the application should be accompanied by a copy of the draft label.
Two additional draft labels are to be attached to the cover-letter.
f) A pesticide sample from each of the sources must be submitted, suitably packed
and clearly labeled with the following information i.e trade name, applicant name,
active ingredient, concentration, type of formulation and the source name. The
quantities required are as follows:
Technical material
Formulated material
Aerosol
Mosquito coil
-50 g or 50 ml
-100 g or 100 ml
- 4 x 100 ml cans or more
- 4 x 10 pieces
8
Mosquito mat
Others
- 2 x 30 pieces
- refer to Pesticides Board
The registration sample must not be submitted in plastic bags in order to avoid
spillage and contamination. Dust/powder or liquid formulations should be placed in
either plastic or glass bottles. For dust or powder formulations, wide-mouthed
bottles fitted with stoppers or seals should be used. Samples should be not sent
by post but should be sent either by hand or by courier service. All imported
samples must be accompanied with an Import Permit endorsed by the Malaysian
Customs.
g) Analytical standard must be submitted for each active ingredient listed in the
application. Analytical standard samples must be accompanied by an Import
Permit (endorsed by the Royal Malaysia Customs Department), Certificate of
Analysis, and information on the date of expiry of the standard must be provided
(date of expiry must not be less than 1 year from date of submission). Some active
ingredients are exempted from submission of analytical standard 1. The
specifications mentioned above for submission of samples also applies to
submission of analytical standards.
h) Each application must be submitted with a copy of the current Certificate of
Registration of the company (ROC/ROB).
i) Banker’s draft/money order/postal order of RM 1,500.00 (one thousand five
hundred ringgit) per application, made payable to the Director General of Agriculture,
as the payment for the application.
__________________________________________________________________________________
*
1
**
2
as per circular B.81/05.20/Jld. V( 25 ) dated 12 Dis. 2008
5 sets as per circular B.81/05.20/Jld. IV(65 ) dated 6 Dis. 2000
9
Re-registration
The validity period of a registration is 5 years. Before the end of the validity period, the
registrant may make an application to re-register the pesticide, and the application
must be submitted not earlier than 1 year BUT not later than 6 months before expiry.
Late submissions to re-register may not be accepted and may necessitate the
pesticide be submitted as a new application.
The following are the requirements for an application for re- registration:
a) One (1)* set of application forms.
b) Four (4) copies of amended draft label.
c) A copy of the current Registration Certificate.
d) The source(s) of a pesticide as approved by the Pesticide Board must be
declared in the cover-letter. In addition, a recent letter of undertaking (not more
than one year from the date of application for re-registration) from the source(s)
confirming that they will continue to be the suppliers of the pesticide should also
be submitted. A maximum of 3 sources will be allowed at any one time provided
the composition and percentage of all the ingredients are identical. An outline
of the manufacturing process from all the sources must be submitted (Please
Refer Annex II, Chapter 1, Item 1.3 and 1.9). Any change of source(s) or
manufacturing process during the period of registration must be approved by
the Pesticides Board, and such evidence must be submitted at re-registration.
e) Data on five batch analysis.
f) A copy of the current Certificate of Registration of the company (ROC/ROB).
g) All information must be on A4 size paper and accompanied by a standard
cover-letter. (See Annex I).
h) Banker’s draft/money order/postal order of RM1,500.00 (three thousand
ringgit) per application made payable to the Director General of Agriculture as
payment for the application.
10
How To Complete The Application Form
The Application Form is divided into 7 parts i.e. A, B, C, D, E, F and G and all parts
must be completed.
For Part E, however, depending on the general use pattern of the pesticide (whether
proprietary or commodity) some studies or information/data may be waived. To assist
the applicant in providing the right data/information to support the application to
register or re-register a pesticide, Annex II provides a summary of data requirements
for different types of pesticides.
In addition to the above, the applicant should also refer to the following guidelines for
detailed information on how such data/studies should be generated and compiled:
i)
ii)
iii)
iv)
v)
Guidelines on Product Chemistry Data Requirements For Pesticide Registration
(GP 1)
Guidelines on Toxicological Data Requirements For Pesticide Registration (GP
2)
Guidelines on Efficacy Data Requirements For Pesticide Registration (GP 3)
Guidelines on Residue Data Requirements For Pesticide Registration (GP 4)
Syor-Syor Kawalan Diluluskan Untuk Racun Perosak Komoditi (GP 5)
LABELLING REQUIREMENTS
The label represents an important source of information to the user of a pesticide. A
label is the written, printed or graphic material firmly attached to a product container.
Among others, the label should contain the identity of the pesticide and instructions on
use, precautions to be taken and other relevant information. This is to ensure that the
pesticide is used properly and effectively. Under the Pesticides Act 1974, a pesticide
shall not be sold unless it is registered and labelled with an approved label. To ensure
proper labelling of pesticides sold in the country, the Pesticides (Labelling)
Regulations 1984 have been gazetted and should be used. As part of the process of
approving an application for registration, the proposed label of a pesticide is evaluated
to ensure that it complies with the requirements of these regulations. To comply with
the labelling requirement, therefore refer to the Pesticides (Labelling) Regulations
1984. For guidance, the applicant is advised to refer to Annex III which provides two
layout examples that meet the requirement of the Pesticides Board.
The applicant should also refer to the latest edition of ‘Garis Panduan Untuk Nama
Dagangan Racun Perosak’ in order to ensure trade name given to the pesticide is
acceptable to the Pesticides Board.
11
MANUFACTURING FOR EXPORT PURPOSES
Registration approval under the Pesticides (Registration) Rules 2005 is only meant for
all activities to import and manufacture pesticides intended for local market and sale.
However, if the pesticide is solely manufactured for export, registration approval is not
required, provided it contains an active ingredient which is at the time registered with
the Pesticides Board. It is the duty of the manufacturers to check with the Pesticides
Board, to confirm if such an active ingredient is already registered in Malaysia.
IMPORTATION OF AN UNREGISTERED PESTICIDE
An unregistered pesticide may only be imported in a limited quantity for educational or
research purposes, or as a registration sample or in the form of analytical standard by
means of a import permit as provided for under the Pesticides (Importation for
Educational and Research Purposes) Rules 1981. Copies of the "Guidelines on
Application for Permit to Import Pesticides for Educational and Research Purposes" are
available from the Secretary of the Pesticides Board upon request.
PENALTIES
It is illegal under the Pesticide Act 1974, to import and/or manufacture pesticides
without any valid registration approval from the Pesticides Board. Any person, if found
guilty of importing or manufacturing any pesticide without valid registration approval, is
liable on a first conviction, to imprisonment for 5 years or to a fine of RM50,000 and,
on a second or subsequent conviction, to imprisonment for 10 years or to a fine of
RM100,000 or both.
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Annex I
THIS STANDARD COVER LETTER IS TO BE
TYPED ON APPLICANT'S COMPANY LETTERHEAD
Date :
Secretary
Pesticides Board
4th Floor, Wisma Tani
Jalan Sultan Salahuddin
506320 Kuala Lumpur.
Dear Sir,
APPLICATION TO REGISTER/RE-REGISTER PESTICIDE
Herewith is an application to register/re-register *
__________________________________________________________________
(state trade name)
(please tick whichever is applicable)
[___] Commodity Pesticide
[___] Proprietary Pesticide
[___] New Registration
[___] Re-registration
LRMP/R1 No. : ........................
File No. : JP KRP 207/12/171/.............
[___] 5 set of application (Form A)
[___] 1 set of application (Form A)
5 sets with 1 original set of data
[___] Data on five batch analysis
requirements (Part E- Form A)
1 copy of proposed label in
[___]
[___] 1 Photostat copy of endorsed printed label
each set
2 copies of proposed labels
[___]
[___]
copies of amended draft labels
attach with cover letter.
[___]
Copy of current Registration Certificate
[___]
13
APPLICABLE TO REGISTRATION & RE-REGISTRATION
[___]Sample suitably packed and labeled. (With copy of Import Permit, if necessary)
[___]Sample of analytical standard suitably packed and labeled. (With copy of Import
Permit, if necessary)
[___]Letter of certification from source of the pesticide.
[___]Letter of authorization on the use of data.
[___]Copy of company registration (ROC/ROB)
The source(s) (Name and address) of the above pesticide are:
1. _________________________________________________________________
____________________________________________________________________
2. _________________________________________________________________
____________________________________________________________________
3. _________________________________________________________________
____________________________________________________________________
Thank you.
Yours faithfully,
___________________
(Name and Signature of
applicant & Company stamp)
14
Annex II
SUMMARY OF DATA REQUIREMENTS FOR PROPRIETARY AND COMMODITY
PESTICIDES ACCORDING TO GENERAL USE PATTERN
(REFER APPLICATION FORM,
PART E: PARTICULARS ON DATA REQUIREMENTS)
General Use Pattern
NonFood
Commodity
Indoor
/ House
hold
CHAPTER 1:
IDENTITY, PHYSICAL
AND CHEMICAL
PROPERTIES
Part A : Requirement On
Technical Active Ingredient
1.1 Identity
-
-
-
-
-
√
1.2
Chapter
Food
Commodity
Out
Door
Technical
Forestry material
Physical and chemical
properties
1.3 Manufacturing process
(including raw
materials used and byproducts and impurities
in the finished
products)
1.4 Identity and amounts
of isomers, impurities
and other by-products,
together with
information on their
possible range.
1.5 Data on five batch
analysis including the
profile of impurities
and chromatogram.
1.6 Material Safety Data
Sheet (MSDS).
Part B : Requirement On
The Formulation (if
relevant)
1.7 Identity
-
-
-
-
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√
-
-
-
-
-
√
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-
-
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√
-
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1.8
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-
Physical and chemical
properties
1.9 Specifications of the
product (indicate
whether it meets any
specifications e.g.
Malaysian Standard,
FAO/WHO
specification or others)
Notes
Also required for re-registration
15
General Use Pattern
Chapter
1.10 Manufacturing process
and quality control
1.11 Storage stability test
(FAO Accelerated
Storage Test
Procedures may be
employed).
1.12 Material Safety Data
Sheet (MSDS).
1.13 Specific properties
depending on
formulation type (e.g.
wettability, persistent
foaming,
suspensibility, wet
sieve test, dry sieve
test, emulsion stability,
corrosiveness).
1.14 Known compatibility
with other pesticides.
1.15 Packaging (including
packaging material and
its compliance to any
standarts or
specifications)
1.16 Data on five batch
analysis of the active
ingredient including
chromatogram (if
applicable)
Food
Commodity
NonFood
Commodity
Indoor
/ House
hold
√
√
√
√
√
-
√
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√
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√
√
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√
√
√
-
√
√
√*
√
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√
√
√
√
√
-
√
√
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√
√
-
Out
Door
Technical
Forestry material
Notes
Not required for ready to use
products
Not required for new
registration
16
General Use Pattern
Chapter
CHAPTER 2 :
METHOD OF ANALYSIS
2.1 Validated methods of
analysis of active
ingredient in the
technical material
2.2 Validated method of
analysis of active
ingredient content in the
formulation
analysis of content of
impurities in the
technical material and
formulation.
analysis for residue of
the active ingredient
and all important
metabolites in all
relevant matrix of the
crops.
analysis for residue of
the active ingredient
and all important
metabolites in
environmental media.
Food
Commodity
NonFood
Commodity
Indoor
/ House
hold
-
-
-
-
-
√
√
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√
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√
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Out
Door
Technical
Forestry material
Notes
Where it is applicable
17
General Use Pattern
Chapter
CHAPTER 3 :
IMPACT ON HUMAN
AND ANIMAL
(MAMMALIAN
TOXICOLOGICAL
DATA)
Food
Commodity
NonFood
Commodity
Indoor
/ House
hold
Out
Door
Notes
Technical
Forestry material
To submit requirements of Part A or Part B or both.
To submit either Part A or Part B. Submission of both Parts A & B (i.e Data on Technical and Formulation)
is also acceptable. However, if any of the a.i(s) in the formulation is proprietary, submission of Part B (if
selected) must include data requirements Part A (3.2) to A(3.5). These data may be based on either the
technical a.i(s) or formulated product.
- Laboratory performing toxicology studies must comply with the standards of Good Laboratory Practices
(GLP).
- GLP Certificate issued by the Compliance Monitoring Authority (CMA) national authorities or bodies
accredited to monitor compliance with the Principles of GLP toxicity studies must be attached.
- For the registration application can't meet GLP requirements, the Pesticide Board may give special
consideration to the application if requested products have specific needs and interests of the nation.
*Please refer secular dated 25 Feb 2013.
PREMIXTURE ACTIVE INGREDIENT
- food crop usage (insecticide/fungicide): mandatory toxicology data on MIXTURE
- herbicide : toxicology data on single active ingredient is acceptable.
SINGLE ACTIVE INGREDIENT
- toxicology data on technical grade or finish product is acceptable
Part A: Requirement On
Technical Active
Ingredient
3.1 Acute toxicological
data
3.1.1 Acute oral
studies (in rats)
3.1.2 Acute dermal
studies (in rats)
3.1.3 Acute inhalation
studies (in rats)
√
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3.1.4 Skin irritation
studies (in
rabbits).
√
√
√
√
√
√
3.1.5 Eyes irritation
studies (in
rabbits).
√
√
√
√
√
√
√
√
√
√
√
√
√
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√
3.1.6 Dermal
sensitisation
study (in guinea
pigs).
3.1.7 Acute delayed
neurotoxicity in
hens (for
organophophates
and carbamates)
Not required for commodity
pesticide, unless studies indicate
significant exposure through this
route
route
route
route
pesticide
18
General Use Pattern
Chapter
Food
Commodity
NonFood
Commodity
Indoor
/ House
hold
Out
Door
Technical
Forestry material
Notes
pesticide, unless acute toxicity
profile indicates that there is a
strong possibility that sub-acute
exposure can result in significant
negative effects.
3.2 Sub-acute toxicological
data
3.2.1 Repeated dose 21 or √
28 days dermal
toxicity (in rats)
3.2.2 Repeated dose 28
√
days oral delayed
neurotoxicity in hens
(organophosphates
and carbamates if
triggered by findings
of acute delayed
neurotoxicity).
3.2.3 Sub-acute 90 days
√
dietary feeding study
(in rats)
3.3 Chronic toxicological
data
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3.3.1 Chronic dietary
feeding study (24
monts in rats,
18monts in mouse
and 1 year in
dogs).
3.3.2 Oncogenicity
study (not less
than 24 months
for rats and
18months for
mouse. This study
can be combined
with chronic
feeding study, if
appropriate).
3.4 Supplemental
toxicological studies
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√
3.5 Teratogenicity study (2
species, one redent and
one non-rodent)
√
pesticide, unless acute and subchronic toxicity profile indicates
that there is a strong possibility
that chronic exposure can result
in significants negative effects.
Not required for commodity,
unless its toxicity profile/ use
recommendations indicates that
there is a strong possibility that
exposure can result in long-terms
significant negative effects in
relation to the aspects as stated
below.
√
√
√
√
√
19
General Use Pattern
Food
Commodity
NonFood
Commodity
Indoor
/ House
hold
3.6 Reproductive study (2
generations of rodents
and one litter).
3.7 Mutagenicity study (at
least in 3 battery of
tests to detect gene
mutation, chromosomal
aberration and
genotoxic effects)
3.8 Metabolic study (at
least one species)
3.9 Human toxicology data
(such as industrial
exposure data,
accidental data or
volunteer data).
3.10 Toxicological
information of every
ingredient, synergist,
and major or important
impurity of the
pesticides.
Part B : Requirement On
The Formulation (if
applicable)
3.7 Acute oral toxicity
study in rats.
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
√
Optional unless requested
√
√
√
√
√
√
pesticide
√
√
√
√
√
-
3.8 Acute dermal toxicity
study in rates.
√
√
√
√
√
-
3.9 Skin irritation study in
rabbits
√
√
√
√
√
-
3.10 Eye irritation study in
rabbits
√
√
√
√
√
-
3.11 Skin sensitisation study
in guinea pigs.
√
√
√
√
√
-
Preferred studies, in additions
to studies on technical
material (Refer 3.1.1.)
Preferred studies, in additions
to studies on technical
material (Refer 3.1.2.)
pesticide, unless studies
indicate significant exposure
through this route.
through this route.
through this route.
3.12 Acute inhalation study
in rats (if applicable)
√
√
√
√
√
-
Chapter
Out
Door
Technical
Forestry material
Notes
Not required for commodity,
unless studies indicate
significant exposure through
this route.
20
General Use Pattern
Chapter
CHAPTER 4 :
RESIDUE
4.1 Definitions of the
residue to Maximm
Residue Limits
(MRLs)
4.2 Detailed reports on
supervised residue trial
on recommended crops
based on accepted
protocols (e.g. FAO
Manual on the
Submission and
Evaluation of Pesticide
Residue Data for the
Estimation of
Maximum Residue
Limits in Food and
Feed, FAO, UN 2002).
Studies conducted
under similar climatic
conditions may be
submitted.
4.3 Residue analytical
method with
chromatograms for
standard, control,
sample and recovery
test.
4.4 Information on
metabolism or
degradation of the
active ingredient in
crops or plants
4.5 Acceptable Daily
Intake (ADI) of the
pesticide in mg/kg
body weight.
4.6 Proposed Pre-harvest
interval (PHI) or PreSlaughter Interval
(PSI)
4.7 Proposed Maximum
Residue Limits
(MRLs) calculated
based on Dietary Risk
Assessment of the
pesticide.
4.8 Maximum Residue
Limits (MRLs) from
other countries that
have registered the
pesticide
Food
Commodity
NonFood
Commodity
Indoor
/ House
hold
Out
Door
Notes
Technical
Forestry material
No required if it is recommended on 16th Schedule (Regulation 41)
√
-
-
-
-
-
√
-
-
-
-
-
At least three field experiments
done at different sites must be
submitted.
* please refer 16th Schedule
(Regulation 41)
For a major crop, which is oil
palm, cocoa, paddy and black
pepper, at least one field
experiment must be generated
under local conditions.
√
-
-
-
-
-
Analytical method by crop
√
-
-
-
-
-
Mandatory for proprietari a.i.
√
-
-
-
-
-
ADI by a.i
√
-
-
-
-
-
PHI by crop
√
-
-
-
-
-
Proposed MRL by crop
√
-
-
-
-
-
MRL by crop
21
General Use Pattern
Chapter
CHAPTER 5 :
FATE AND BEHAVIOUR
IN THE ENVIRONMENT
5.1 Definition of the residue
relevant to the
environment
5.2 Degradation and
dissipation studies
(hydrolysis, photolysis
in water and soil)
5.3 Metabolism studies (in
water and soil for both
aerobic and anaerobic
conditions).
5.4 Mobility studies
(leaching and
adsorption or
desorption studies,
volatility in laboratory
and field).
5.5 Fate and behaviour in
air.
5.6 Bioaccumulation study
in fish
Food
Commodity
NonFood
Commodity
Indoor
/ House
hold
Out
Door
Technical
Forestry material
Notes
pesticide
√
√
-
√
√
-
√
√
-
√
√
-
√
√
-
√
√
-
√
√
-
√
√
-
√
√
-
√
√
-
√
√
-
√
√
-
22
General Use Pattern
Chapter
Food
Commodity
CHAPTER 6 :
EFFECTS ON NON
TARGET SPECIES
6.1 Effects on terrestrial
√
vertebrates (including
acute oral toxicity to
avian species e.g.
pigeon, quail, pheasant,
or duck).
6.2 Effects on aquatic
species
6.2.1. Acute LC50, 96
√
hours exposure
on the suitable
fish species.
6.2.2. Acute LC50, 48
√
hours exposure
on one suitable
fish-food species
e.g. daphnia
6.3 Effects on bees and
√
other arthropod species
(including acute oral
LD50, and contact
toxicity on honey bees)
6.4 Effects on earthworms
√
and other soil macroorganisms (including
acute toxicity on
earthworms).
6.5 Effects on other non√
target organisms (flora
and fauna)
NonFood
Commodity
Indoor
/ House
hold
√
-
√
√
-
√
-
√
√
-
Out
Door
Notes
Technical
Forestry material
√
-
√
√
-
√
-
√
√
-
√
-
√
√
-
√
-
√
√
-
23
CHAPTER 7 :
EFFICACY DATA
AND INFORMATION
All reports submitted must be very recent and shall not be more than 15 years from the date of
submission.
- Not required for HERBICIDE if the active ingredient and its formulation is listed in GP5.
*Please refer latest secular dated 26 Feb 2013.
Journal data on bio-efficacy trial is acceptable.
* Not required for veterinary
products.
7.1 Local Bio-efficacy
trials on the
recommended crops
based on the accepted
protocols (e.g. FAO
Harmonized Bioefficacy Protocols).
Trials conducted under
similar climatic regime
and cultural practices
may be used for minor
crops)
√*
7.8
-
-
√
-
- For a major crop, which is oil
palm, cocoa, paddy and black
pepper, one field experiment
(with multiple replicates) must
submit bio-efficacy trial
generated under local conditions.
- For Non major crop, bioefficacy trial from overseas is
acceptable.
7.2 Phytotoxicity
assessment on crops
based on accepted
protocols (e.g. FAO
Guidelines for
Phytotoxicity
Assessment)
7.3 Effects on natural
Enemies
7.4 Information on
potential occurrence to
resistance
7.5 Comparative study
using Malaysian
Standard or other
internationality
accepted protocols for
all non-agriculture
pesticides
7.6 Information on mode of
action and its grouping.
7.7 Propose use(s) and
Recommendation in
tabulated form
- tabulated format
√
- Must submit bio-efficacy trial
data for each crop.
products.
√*
√
-
-
√
-
√*
√
-
-
√
-
√
√
-
-
√
products.
* Not required for agricultural
products.
√*
-
√
√
-
-
√
√
√*
-
√
-
* Not required for household
pesticides.
√
√
√*
√
√
-
*depending on the type of
usage
statement format
[ KEY : (√ ) = Required; ( √* ) = Conditionally required and (-) = Not required ]
24
EXAMPLES OF GENERAL USE PATTERNS
Food commodity


Agricultural crops for human
consumption
Veterinary
Indoor / Household



Non-food commodity






Crop for smoking
Ornamental plants
Lawn and turf grasses
General soil treatments
Recreational areas
Roads, tracks and paved areas
Household Pesticides
Rodenticides for household
use
Pet animals pesticides
Outdoor




Wood treatments
Antifouling treatments
Public health
Preservative
Forestry



Forest trees including dead trees,
logs and stumps
Forest tree nurseries
Non-ornamental trees including
rubber trees
Technical material

Technical material for
manufacturing purposes
25
26
27
28
AKTA RACUN MAKHLUK PEROSAK, 1974
Garis Panduan (Pelabelan) 2003
KEHENDAK-KEHENDAK PELABELAN
Maklumat
Tiap-tiap racun makhluk perosak hendaklah mempunyai label yang mengandungi maklumat
yang berikut:Maklumat pada Panel Utama
Maklumat minimum yang perlu dicetak pada panel utama label:
1. Nama Dagangan
Nama Dagangan atau nama kepunyaan racun makhluk perosak dan nama
itu hendaklah sama seperti yang ditetapkan dalam perakuan pendaftaran racun makhluk
perosak. Perbezaan ketinggian huruf mestilah tidak melebihi 30 % dan perlu dicetak dalam
jenis serta bentuk font di samping warna, format dan kepekatan yang sama.
2. Perumusan
Perumusan racun makhluk perosak hendaklah sebagaimana
ditetapkan dalam
perakuan pendaftaran racun makhluk perosak. Ia hendaklah dicetak dalam huruf besar tanpa
ditebalkan.
Contoh: PEKATAN TEREMULSI (EC), CECAIR (TEKNIKAL),
3. Kegunaan
Pernyataan kegunaan sesuatu racun seperti racun rumpai, racun serangga, racun kulat
dan sebagainya termasuklah produk teknikal hendaklah dicetak dalam huruf besar tanpa
ditebalkan.
Contoh: RACUN SERANGGA, RACUN RUMPAI.
Bagi produk teknikal, pernyataan ‘RACUN MAKHLUK PEROSAK’ hendaklah
dicetak pada label. Cetakan juga hendaklah dalam huruf besar tanpa ditebalkan. Untuk
produk teknikal juga, kegunaan diganti dengan frasa seperti di bawah. Cetakan hendaklah
dalam huruf besar dan ditebalkan.
29
GRED TEKNIKAL UNTUK TUJUAN PERKILANGAN SAHAJA
Bagi produk untuk “Pest Control Operator” (PCO) yang tertentu, pernyataan ‘UNTUK
DIKENDALIKAN OLEH ORANG YANG TERLATIH SAHAJA’ hendaklah dicetak pada
label dalam huruf besar dan ditebalkan.
Bagi produk untuk kegunaan industri seperti cat beracun untuk kayu-kayan, pernyataan
UNTUK KEGUNAAN INDUSTRI SAHAJA hendaklah dicetak dalam huruf besar dan
ditebalkan.
4. Pernyataan Bahan-Bahan
Nama biasa bagi bahan aktif hendaklah diikuti dengan bahan lengai (jenisnya tidak
perlu dinyatakan) dengan peratusannya mengikut berat dan kandungan bahan hendaklah
dinyatakan sebagai % w/w (% berat/berat). Bagi racun makhluk perosak jenis lain, kandungan
perawis atau bahan hendaklah sepertimana yang tetapkan oleh Lembaga.
Abjad pertama bagi nama biasa tidak boleh menggunakan huruf besar jika abjad seterusnya
adalah dalam huruf kecil.
contohnya: Glyphosate isopropylamine - tidak diterima
glyphosate isopropylamine - boleh diterima
Cetakan hendaklah dalam huruf tebal sepertimana contoh di bawah:
Perawis Aktif : aaaaaa bbbbbb.................................. 00.0 % w/w
(aaaa................0.00 % w/w)
Perawis Lengai : ........................................................ 00.0 % w/w
5. Nama dan Alamat Syarikat
Hanya nama dan alamat syarikat yang mendaftar racun perosak perlu dinyatakan.
Penyata ‘Didaftarkan oleh:’ perlu dicetak dan masukkan No. Syarikat dan No. Telefon.
Penggunaan alamat peti surat tidak dibenarkan. Pastikan saiz cetakan tidak kurang dari 9 poin.
Alamat website adalah tidak dibenarkan dicetak pada label.
6. Nombor Pendaftaran
Nombor pendaftaran racun makhluk perosak sebagaimana yang ditetapkan oleh
Lembaga. Ia hendaklah dicetak dalam huruf tebal seperti berikut:
No. Pendaftaran: LRMP. R1/XXXX.
30
7. Kandungan Bersih
Kandungan bersih racun makhluk perosak, tidak termasuk
pembungkus
atau pembalut hendaklah dinyatakan mengikut isi padu atau berat sebagaimana disyaratkan
oleh Lembaga. Kandungannya hendaklah dinyatakan sebagai kuantiti minimum.Bilangan dan
berat bersih isi kandungan bagi setiap bungkusan kecil dalaman seperti pipette, sachet dan lainlain hendaklah dicetak pada label. Cetakan tanpa ditebalkan.
Contoh: Kandungan Bersih: 20 liter
8. Tarikh Mengilang
Tarikh mengilang sebenar racun makhluk perosak hendaklah dicetak pada label.
Cetakan boleh dibuat pada mana-mana bahagian label tanpa ditebalkan.Tarikh luput bagi
produk yang tempoh luput kurang daripada 2 tahun juga hendaklah dicetak pada label.
Penggunaan label pelekat adalah tidak dibenarkan.
Contoh: Tarikh Mengilang:
Maklumat-maklumat yang perlu dicetak pada lain panel
9. Pernyataan Penyimpanan dan Pembuangan
i)
Tatacara penyimpanan, Pembuangan Sakibaki racun serta maklumat-maklumat berhubung dengan tindakan yang perlu
dilaksanakan sekiranya berlaku kebocoran, tumpahan atau kerosakan pada racun makhluk perosak.
ii)
Pembuangan bekas. Di samping pernyataan rasmi pembuangan bekas, arahan
menghendaki pengguna terlebih dahulu melaksanakan proses pembersihan
secara membilas tiga kali. Bagi perumusan aerosol, frasa perihal pembuangan
bekas digantikan dengan “JANGAN TEBUK ATAU BAKAR BEKAS
AEROSOL”. Bagi perumusan kepingan dan lingkaran, perkara (9)(ii) adalah
dikecualikan.
10. Aturan Penggunaan (Contoh: Lihat lampiran 1)
Melainkan bahan-bahan teknikal atau mana-mana bahan yang ditetapkan oleh
Lembaga, label racun makhluk perosak hendaklah mengandungi arahan-arahan yang cukup
dalam bentuk jadual berhubung dengan aturan penggunaannya.
Ini termasuk maklumat-maklumat berhubung dengan cara membancuh, cara
menggunakannya, jarak masa dan kekerapan semburan atau rawatan. Ini diikuti dengan
pernyataan tempoh dilarang mengutip hasil atau menyembelih ternakan atau meragut rumput
atau mengedar selepas semburan atau rawatan terakhir racun makhluk perosak. Di mana
berkenaan tempoh masa masuk semula dan bilangan semburan maksimum semusim juga perlu
dinyatakan.
Maklumat-maklumat lain pada label termasuklah piktogram-piktogram berkaitan dan
butir-butir lain yang releven mengenai sifat fizik dan biologi racun makhluk perosak
berkenaan.
31
11. Pernyataan Awas (Contoh: Lihat
lampiran 2)
Pernyataan ini merangkumi langkah-langkah keselamatan bagi tujuan menghalang
berlakunya sebarang bencana terhadap manusia dan alam sekitar. Ia perlu dijelaskan secara
terperinci di bawah perkara-perkara berikut:
(i)
bahaya kepada manusia. Penekanan hendaklah diberi berhubung dengan
kemungkinan bahaya disebabkan termakan atau terminum, serapan kulit,
terhidu dan lain lain bersangkutan. Pernyataan berkaitan bentuk atau jenis
pakaian serta peralatan perlindungan yang perlu diguna ketika
mengendalikannya juga perlu dijelaskan.
(ii)
bahaya pada alam sekitar. Tumpuan perlu diberi terhadap kesan keracunan
pada binatang atau hidupan liar atau tumbuhan berfaedah dan berguna
selain sumber atau saliran atau kawasan tadahan air. Ini termasuk
pernyataan jarak zon larangan penggunaan racun makhluk perosak bagi
kawasan- kawasan berhampiran dengan sumber air ataupun kawasan
tadahan air. Lembaga boleh menetapkan pernyataan awas yang lain atas
alasan kepentingan awam.
12. Pengelasan Racun Perosak/Pita Warna
Setiap label hendaklah menunjukkan pita warna berdasarkan pada kelas yang
diperuntukkan oleh Lembaga termasuk kata hemat, pernyataan dan simbol-simbol amaran yang
dihubungkaitkan dengan kumpulan kelas serta sifat-sifat bahan berkenaan.
Kelas yang ditetapkan bagi racun makhluk perosak iaitu KELAS Ia, KELAS
Ib,KELAS II, KELAS III atau KELAS IV hendaklah dicetak dalam huruf besar dan tebal
ditengah-tengah pita warna dengan cetakan berada di kawasan ruang panel utama. Pita warna
hendaklah dicetak di sekeliling bahagian label yang paling bawah dan hendaklah mempunyai
ketinggian minimum berukuran 10 peratus daripada keseluruhan ketinggian label dengan
syarat bahawa saiz font cetakan huruf-huruf itu tidaklah kurang daripada 9 poin serta
mengadakan simbol-simbol amaran yang diperuntukkan bagi kelas atau sifat racun makhluk
perosak berkenaan.
13. Amaran & Kata Hemat
Pernyataan mengenai amaran dan kata hemat yang sesuai bagi kelas yang ditetapkan
bagi racun makhluk perosak sebagaimana dinyatakan hendaklah dicetak dalam Bahasa
Malaysia dan tiga lagi bahasa tempatan pada pita warna.
Contoh: JAUHKAN DARIPADA MAKANAN DAN KANAK-KANAK
14. Maklumat-maklumat lain
Suatu pernyataan ringkas mengenai tanda keracunan, rawatan kecemasan dan rawatan
perubatan.hendaklah dicetak pada label. Bagi pernyataan rawatan perubatan, ia perlu dicetak
dalam versi Bahasa Malaysia dan Bahasa Inggeris.
32
14.1. Jenis ‘Font’ dan Bahasa
‘Font’ yang disyorkan untuk cetakan ialah jenis ‘Bookman’ pada saiz
sekurang-kurangnya 9 ‘poin’. Pastikan bahasa Malaysia yang digunakan adalah
menurut kaedah semasa. Semua ejaan, tanda bacaan(punctuations), gaya
bahasa(expressions) dan maklumat-maklumat dicetak dengan betul dan sempurna.
14.2. Keperluan untuk ‘Extended Label’
Sekiranya label yang dicadangkan mengguna bentuk persembahan ‘extended
label’, pastikan pernyataan berikut dicetak pada panel yang melekat pada
pembungkusan produk. Tertakluk pada ruang sedia ada, turutan pernyataan menurut
keutamaan yang perlu dicetak adalah AWAS, TANDA TERKENA RACUN,
RAWATAN KECEMASAN, RAWATAN PERUBATAN & MEDICAL
TREATMENT baru diikuti dengan PERNYATAAN PEMBUANGAN.
Disamping itu, pastikan juga maklumat asas lain seperti Perawis Aktif
(termasuk % w/w), Perumusan, No. Pendaftaran , Nama Dagangan dan Nama Syarikat
yang mendaftarkannya serta No. telefon syarikat (tanpa alamat) dicetak sekali lagi pada
panel tersebut termasuk pita warna kelas sekiranya bentuk persembahan panel utama
label berkenaan tidak melekat pada pembungkusan yang dimaksudkan. Pastikan bentuk
persembahan termasuk saiz label yang dikemukakan, adalah sama seperti label yang
akan digunakan pada pembungkusan produk berkenaan.
14.3. Penggunaan Logo
Hanya logo syarikat dan logo produk sahaja dibenarkan dicetak pada label.
Logo syarikat hendaklah dicetak pada ruang sebelah kanan atau kiri nama & alamat
syarikat yang mendaftar. Ketinggian logo ini tidak boleh melebihi ketinggian ruang
cetakan nama & alamat syarikat. Logo produk boleh dicetak sama ada disebelah kanan
atau kiri nama dagangan dengan ketinggian logo tidak melebihi 50% daripada
ketinggian huruf nama dagangan. Cetakan kedua-dua logo tidak boleh berulang
walaupun logo yang sama. Logo-logo lain tidak dibenarkan iaitu termasuk Logo
SIRIM, ISO dan sebagainya melainkan mendapat kelulusan di mana tempoh kelulusan
adalah sama atau labih dengan tempoh kelulusan racun perosak yang didaftarkan..
Sebarang bentuk promosi ataupun yang dianggap berunsur iklan adalah tidak
dibenarkan dicetak pada label
15. Pihak Lembaga adalah berhak untuk membuat sebarang tambahan atau
perubahan dalam Garis Panduan ini dari semasa ke semasa jika difikirkan
perlu.
33
LAMPIRAN 2
CONTOH CORAK LABEL KELUARAN
Panel Utama
Panel Kedua dan seterusnya
ATURAN PENGGUNAAN: Pra Pengenalan…………………………………………………
NAMA DAGANGAN-XXX*
Perawis Aktif: ........................................................ % w/w
Perawis Lengai: ..................................................... % w/w
Penggunaan tidak mengikut label adalah satu kesalahan.
KADAR RACUN
KAWASAN
TANAMAN
........................
JENIS RUMPAI
…………………
10 liter air
sehektar
……….
………
ISIPADU
SEMBURAN
SEHEKTAR
………
Pernyataan di larang mengutip hasil/masuk semula kawasan (jika berkaitan)............
Panduan Membancuh
KEGUNAAN
PERUMUSAN
Panduan Menyembur
Didaftarkan oleh:
No. Pendaftaran: LRMP.R1/ ….
Syarikat ABCDEF Sdn Bhd (No:123456X)
Kandungan Bersih: …Liter
111, Jalan XYZ
Bandar DEFGH
00000 Kuala Lumpur.
Tarikh Mengilang:
Tel: 03-12345678
Faks: 03-21345678
PUSAT RACUN NEGARA - 1-800-88-8099 (waktu pejabat)
- 012-4309499 (lepas waktu pejabat)
BACA LABEL SEBELUM GUNA
Pernyataan Amaran &
Kata hemat versi
Bahasa Mala ysia
KELAS X
Tempoh Dilarang Masuk Semula Kawasan Rawatan (REI): … jam
AWAS: a) Bahaya Kepada Manusia:.............................................
Pakaian dan Alat Perlindungan:...................................
b) Bahaya Pada Alam Sekitar:..........................................
TANDA KERACUNAN:.................................................................
RAWATAN KECEMASAN:.............................................................
RAWATAN PERUBATAN: .............................................................
MEDICAL TREATMENT:...............................................................
JANGAN GUNAKAN BEKAS RACUN UNTUK MENYIMPAN MAKANAN. TANAM
BEKAS RACUN APABILA KOSONG.
Versi Bahasa
Tempatan II
Versi Bahasa
Tempatan III
Versi Bahasa
Tempatan IV
Catatan: Format jadual Aturan Penggunaan hendaklah diubahsuai mengikut jenis produk yang hendak didaftarkan. Lambang tengkorak
hanya bagi produk Kelas Ia & Ib sahaja
34
GP 1/93
GUIDELINES ON
PRODUCT CHEMISTRY DATA REQUIREMENTS
FOR
PESTICIDE REGISTRATION
Pesticides Board
Malaysia
2009
35
Product Chemistry Data Requirement for
Pesticide Registration
__________________________________________________
A.
Introduction
Data requirements on product chemistry include information on product composition,
chemical and physical properties of the pesticide. These data among other things are
required to:
a)
support the claims made by the applicant;
b)
enable registration authorities to evaluate the pesticide in terms of its
quality, potential hazards, decomposition products etc;
c)
enable registration authorities to evaluate the pesticide and specify
labelling and packaging requirements; and
d)
support emergency requests on spillage, fire, poisoning etc.
B.
Requirements
1.
Manufacturing Process
The manufacturing activity should be stated clearly.
An outline of the process of manufacturing the pesticide should be submitted
with the application.
For technical materials, the manufacturing process starting from the raw
materials should be provided.
Chemical equations for chemical reactions involved in the manufacturing
process should also be provided.
The presence and concentration of any by-products in the finished product
should be indicated.
36
2.
Common Name
The common name of the active ingredient(s) should be clearly stated as listed
in First Schedule (Section 2) of the Pesticides Act 1974.
If no common name is listed, then the common name accepted by SIRIM or
ISO should be used. If this is not available then the common name proposed by
other organisations (BSI, JMAF etc.) may be used.
For products containing Bacillus thuringiensis or similar active ingredients, the
subspecies and strains of the organism should be given.
3.
Chemical Name
The IUPAC (International Union of Pure and Applied Chemistry) chemical
name should be used.
4.
Structural Formula
The structural formula of the active ingredient including its salt or ester
wherever applicable should be provided.
5.
Additional Information on the Active Ingredients
Proprietary names, synonyms and code names to be provided as a guide to
identify the products.
Chemical and physical properties of the technical material should be
provided. (Refer Appendix 1)
The Material Safety Data Sheet of the product should be provided. (Refer
Appendix 2 for details of data required)
The concentration of the active ingredient in the product to be registered
should be expressed in % w/w of mg/mat or i.u./mg whichever is applicable.
6.
Percentage Composition of the Pesticide
The concentration of technical materials used should be indicated.
The identity of every ingredient in the formulated product should be stated and
its concentration given in % w/w or g/kg.
37
7.
Method of Analysis
Analytical procedures for determination of the content of active ingredient and
content of impurities of toxicological concern in the product should be provided.
Procedures involving use of carcinogenic reagents would not be acceptable.
Sources or authorities from which the analytical procedures is extracted should
be mentioned.
In addition, analytical standards required for the above should be supplied with
the application for all proprietary products.
8.
Packing
The type of packing material used should be stated.
The packaging should comply with Malaysian Code of Practice for Packaging
and Storage of Pesticide.
If the packaging does not comply with the Malaysian Code of Practice for
Packaging and Storage of Pesticide, the results of a quality evaluation test
should be provided.
Evidence of Stability on Storage
A certificate of analysis as evidence of stability on storage should be submitted
with each application. Stability tests should be conducted in accordance with
the FAO Accelerated Storage Test Procedures usually at 54 ± 2 o C for 14 days
or at ambient temperature (Malaysian) for 2 years.
9.
Specifications
Specifications for the product should be provided. The pesticide should
conform to Malaysian Standard, FAO or WHO specifications whenever such
specifications are available. This should be indicated in the application form.
When such specification are not available, the applicant should state the
specification that the pesticide complies with.
If the pesticide does not comply with any specifications, the reasons for noncompliance must be given with the application. (Refer to Appendix 3 for details
required in the specification of a product).
(for products containing more than one active ingredient, the above
information will be required for each active ingredient).
38
Appendix 1
Relevant Chemical and Physical Properties of technical materials required.
1.
Physical state, colour and odour.
2.
Solubility in water and other solvents
3.
n-octanol/ water partition coefficient.
4.
Minimum and maximum content of active ingredient in g/kg or % w/w
5.
Stability towards oxidising agents and thermal changes.
6.
Identity and amounts of isomers
7.
Impurities and other by products and their possible range expressed in g/kg or
% w/w.
8.
For solids; its melting point.
9.
For liquids; boiling point, vapour pressure, density and viscosity.
39
Appendix 2
The Material Safety Data Sheet (MSDS) of the product should include the following:
1.
Supplier Information
Company name, address, tel. no., name of persons to contact in case of
emergencies both locally and overseas.
2.
Product Identification
Chemical name of product, synonyms, composition, structural formula, CAS
no., other identification no. as required by legislative control in country of
manufacture.
3.
Physical and Chemical Properties
Boiling point, melting point, vapour pressure, vapour density, specific gravity,
water solubility, appearance, odour, evaporation rate, reactivity and stability.
4.
Health Hazard Information
Route of exposure, sign and symptoms of exposure and chronic effect of
exposure.
5.
First Aid Measures
When inhaled, eye contact, skin contact, swallowed and antidote used and
medical treatment.
6.
Toxicological Data
LD50 for oral, dermal and inhalation. Carcinogenicity.
7.
Personal Protection Requirements
Type of protective apparatus required at work place.
8.
Fire Fighting Procedures
Fire extinguishing method and fire extinguishing agent to be used in case
of fire.
9.
Spills, Leakages and Disposal Procedures
Actions to be taken for the above.
10.
Transport Information
Transport instructions for carrier.
40
11.
Ecological Information
Log P values, bioaccumulations and biodegradibility, and hazards to birds,
bees and environment.
12.
Regulatory Informations
Any regulatory informations in country of manufacture.
41
Appendix 3
Specification of Pesticides
The specifications of a pesticide should conform to either the Malaysian Standards,
FAO or WHO specifications wherever available and should include the following,
where appropriate:
1.
Composition of the pesticide (including impurities, by-products, related
products, stating their concentrations)


2.
Physical and Chemical Properties








3.
State in g/kg or % w/w
State the authority or source of method of analysis used in the
determination of the active ingredient content of the product.
Appearance
Physical state
Colour
Specific gravity (for liquid)
Viscosity (for liquid)
Flash point (for liquid)
Acidity, alkalinity or pH
Bulk density
Specific Properties/ Test Related to Use







Wettability (for wettable powder)
Persistent foaming (for formulations applied in water)
Suspensibility (for wettable powder and suspension concentrate)
Wet sieve test (for wettable powder and suspension concentrate)
Dry sieve test (for granules, dust)
Flowability (for dust)
Emulsion stability and re-emulsification (for emulsifiable concentrate)
Others
 Burning time (for mosquito coil)
 Breaking load (for mosquito coil)
 Separation test
 Discharge rate (for aerosol)
 Particle size (for aerosol)
 Corrosiveness (where relevant)
 Incompatibilities with other products
All test methods must be specified and supported by references.
4.
Other Requirements

UV, IR and mass spectra of the technical material should accompany
the specifications.
42
GP 2/93
GUIDELINES ON
TOXICOLOGICAL DATA REQUIREMENTS
FOR
Pesticides Board
Malaysia
2009
43
Toxicological Data Requirement for
__________________________________________________
1.
Introduction
1.1. Toxicological data are submitted for pesticide registration is aimed at defining
possible hazards to man, non-target organisms and the environment.
1.2. Many practical recommendations can be derived from appropriate and through
toxicological data such as hazard classification, restrictions on use, appropriate
precautionary measures necessary to allow safe use, suggestion of appropriate
diagnosis and management of a poisoned person, establishment of Acceptable Daily
Intake (ADI) etc.
2.
General Requirements
2.1. For the purpose of these guidelines pesticides are divided into two classes i.e.
commodity and proprietary pesticides.
2.2.
Commodity pesticides
2.2.1. For commodity pesticides, acute oral and acute dermal toxicity studies
done on rats are required to be submitted. The detailed requirements
are given in Appendix 1.
2.2.2. Full reports of the above studies must be made available at registration.
2.3.
Proprietary pesticides
2.3.1 For proprietary pesticides, toxicological studies required to be submitted
are dependent on the general use pattern and type of pesticide in
question i.e. whether it is a conventional chemical or a microbial
pesticide. The detailed toxicological requirements needed for chemical
and microbial pesticides are given Table A and Table B of Appendix 1
respectively.
2.3.2 Full reports of the above studies must be made available at registration.
2.4. Letter of consent authorizing the applicant to use the data for registration
purposes must be provided if another company’s data is submitted.
44
3.
Acceptable protocol
3.1.
All toxicological studies should be carried out based on internationally
accepted protocols. Toxicological study protocols such as those
produced by The Environmental Protection Agency of United States
(USEPA), Organization for Economic Cooperation and Development
(OECD), the Ministry of Agriculture, Forestry and Fisheries of Japan may
be used.
3.2.
As examples of acceptable protocols, the Pesticides Board has also
come out with minimum requirements for each test protocol as outlined
in Appendix 2 and Appendix 3 which can also be referred.
3.3.
Protocols for acute oral and acute dermal studies are given in more
detail as in Table C and Table D of Appendix 3. This is in order to
provide applicants who wish to generate data locally with complete
guidelines and reporting format.
3.4.
In conducting the toxicological studies, the applicants are required to
rigidly comply with Good Laboratory Practice standards.
4. Exemptions
4.1
The following are pesticides which can be registered without the
submission of toxicological data.
i.
ii.
iii.
iv.
v.
vi.
vii.
viii.
ix.
x.
xi.
boric acid
borax
copper oxychloride
copper sulphate
cupric sulphate pentahydrate
cuprous oxide
cupric hydroxide
sodium dichromate
sulphur
sodium chlorate
phosphorous acid
45
Appendix 1 (Page 1)
TABLE A : TOXICOLOGICAL DATA REQUIREMENTS FOR REGISTRATION OF
CHEMICAL PESTICIDES
Data Required
General Use Pattern
Non
Food Food InOut Fores
Crop Crop door Door
try
Remarks
ACUTE TESTING
Acute oral
Acute dermal
Acute inhalation
Eye irritation
Skin irritation
Dermal sensitization
Acute delayed neurotoxicity
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
(1)
(1), (2)
(3)
R
R
R
R
R
R
R
R
R
CR
CR
CR
CR
CR
CR
(6)
(7)
R
R
R
R
R
R
R
R
CR
CR
R
CR
CR
CR
R
CR
CR
CR
R
CR
(8)
(9)
R
R
CR
R
R
CR
R
CR
R
CR
CR
R
CR
R
CR
CR
CR
CR
CR
CR
CR
R
CR
R
CR
CR
R
CR
R
CR
(13)
(13)
(14)
(14)
(15)
(16)
CR
CR
CR
CR
R
R
CR
CR
CR
CR
CR
R
R
CR
CR
CR
CR
CR
R
R
CR
CR
CR
CR
CR
R
R
CR
CR
CR
CR
CR
R
R
CR
(1)
(4)
SUBACUTE TESTING
90 days feeding study
CHRONIC TESTING
Chronic feeding study
Carcinogenicity study
SPECIAL STUDIES
Teratogenicity
Reproduction
Mutagenicity
Metabolic
Wildlife Hazards
Fish acute toxicity
Other tests on fish
Avian acute oral toxicity
Other tests on avian
Honey bee acute toxicity
Effects on other wildlife
(10)
Human Toxicological Data
Industrial exposure data
Accidental data
Suicidal data
Volunteers data
Poisoning symptoms
Antidote statements
Protective clothing
KEY: R = Required; CR = Conditionally Required;
(11)
(11)
(11)
(11)
(12)
46
Appendix 1 (Page 2)
TABLE B : TOXICOLOGICAL DATA REQUIREMENTS FOR REGISTRATION
OF MICROBIAL PESTICIDES
Data Required
General Use Pattern
Non
Food Food InOut Fores
Crop Crop door Door
try
Remarks
ACUTE TESTING
Acute oral/ pathogenicity
Acute dermal
Acute inhalation
Eye irritation/ infectivity
Skin irritation
Hypersensitivity study
SUBACUTE TESTING
Sub-acute/ pathogenicity
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
CR
CR
CR
CR
CR
(5)
CR
CR
-
-
-
-
(5)
(5)
CR
CR
CR
CR
CR
CR
CR
CR
CR
CR
(5)
(5)
(5)
(5)
(5)
(5)
(5)
(5)
(3)
CHRONIC TESTING
Chronic feeding study
Carcinogenicity study
SPECIAL STUDIES
Teratogenicity
Mutagenicity
Wildlife Hazards
Fish acute toxicity
Other tests on fish
Avian acute oral toxicity
Other tests on avian
Honey bee acute toxicity
Effects on other wildlife
R
CR
CR
CR
CR
CR
R
CR
R
CR
CR
CR
CR
CR
CR
CR
CR
CR
CR
CR
CR
CR
CR
CR
CR
CR
CR
CR
CR
CR
CR
CR
CR
CR
R
R
CR
CR
CR
CR
CR
R
R
CR
CR
CR
CR
CR
R
R
CR
CR
CR
CR
CR
R
R
CR
CR
CR
CR
CR
R
R
CR
Human Toxicologycal
Data
Industrial exposure data
Accidental data
Suicidal data
Volunteers data
Poisoning symptoms
Antidote statements
Protective clothing
KEY: R = Required; CR = Conditionally Required; (-)= Normally Not required
(11)
(11)
(11)
(11)
(12)
47
Appendix 1 (Page 3)
Remarks:
10.
Not required if test material is a gas or is highly volatile.
11.
Not required if test material is corrosive to skin or has pH less than 2 or more
than 11.5.
12.
Required for commodity pesticides if the product consists of, or under condition
of use will result in an inhalable material.
13.
Required if test material is an organophosphate pesticide.
14.
Required if significant signs of infectivity and advers effects are seen in acute
study or unusual persistence of the microbs.
15.
Required if sub-acute study indicates significant toxic effects.
16.
Required if result of mutagenicity study is positive.
17.
Required if exposure to females is significant.
18.
Required if the use of the product is likely to result in human exposure over a
portion of the human lifespan which is significant in terms of frequency of
exposure, magnitude of exposure or duration of exposure (for example;
pesticides for use in treated fabric for wearing, constant release pesticides
used indoor in aerosol form).
19.
Required if, chronic study and carcinogenicity study are required.
20.
Required if, such data are available.
21.
Required if special safety protective clothing are required to be worn when
handling the product.
22.
Required if the product is intended to be applied directly to water or expected to
transported to water from the use site and significant exposure to aquatic
organisms is anticipated.
23.
Required if significant exposure to bird is expected.
24.
Required if significant exposure to honey bees is expected.
25.
Required if significant exposure to other wildlife is expected.
GENERAL USE PATTERNS
Food crops
1.
Agricultural crops for human consumption
2.
Veterinary
Nonfood crops
1.
Crop for smoking and chewing
2.
Medicinal crops
3.
Ornamental plants
4.
Lawn and turf grasses
5.
General soil treatments
6.
Recreational areas
7.
Roads, tracks and paved areas
8.
Antifoulding treatments
9.
Public health
48
Appendix 1 (Page 4)
Indoor
1.
Houseplants pesticides
2.
Household insecticides
3.
Rodenticides for household use
4.
Pet animals pesticides
5.
Commercial and industrial uses
- Eating establishment
- Transportation facilities
- Buildings and structures
6.
Terminate control inside buildings
Forestry
1.
Forest trees including dead trees, logs and stumps
2.
Forest tree nurseries
3.
Non-ornamental trees including rubber trees
Outdoor
1.
Domestic ornamental platings
2.
Termite control outside buildings
3.
Wood treatments
49
Appendix 2 (page 1)
GUIDELINES FOR TOXICITY STUDIES
Test substance for tests
Unless otherwise specified, the technical grade of the active ingredient shall be tested.
For mixtures of more than one active ingredient, the technical grade of each ingredient
shall be tested. Tests on the actual end-use product will also be acceptable.
1.
ACUTE INHALATION TOXICITY STUDY
1.1.
Purpose
The purpose of this study is to provide information on health hazards likely to
arise from short-term exposure to a pesticide via the inhalation route.
1.2.
Test animals
The rat shall be used. The age, sex and numbers are as stipulated in the acute
oral toxicity study.
1.3.
Dose levels and selection
Al least 3 dose levels shall be used and spaced appropriately to produce test
group with a range of toxic effects and mortality rates.The data should be
sufficient to produce a dose-response curve and permit an acceptable
determination of the LC50 value.
1.4.
Exposure conditions
Using inhalation equipment, animals should be exposed for at least 4 hours to
the test substance in graduated concentrations, allowing sufficient time for
chamber equilibrium. Description of the outline of the inhalation equipment and
its operation should be included in the test report.
1.5.
Observation period
This should be at least 14 days. Clinical observations should be carried out at
least once daily.
1.6.
Pathology
Same as stipulated in the acute oral toxicity study.
2.
2.1.
PRIMARY EYE IRRITATION STUDY
Purpose
The purpose of this study is to obtain information on whether a hazard or
hazard are likely to arise from exposure of the eyes to the test substance.
50
Appendix 2 (page 2)
2.2.
Test substance
Strongly acidic (pH 2 or less) and strongly alkaline (pH 11.5 or more) substance need
not be tested.
2.3.
Test animals
At least 6 young adult albino rabbits shall be used.
2.4.
Test procedure
For testing liquids, a dose of 0.1 ml should be used. For solids and pastes, the amount
used should have a volume of 0.1 ml or weight of 0.1 g. Solid or granular substances
should be ground to a fine dust first. The test substance should be placed in the
conjunctival sac of one eye and the lids then held together for about one second. The
other eye remains as a control.
The eyes of the test animal should not be washed out for 24 hours following
application of the dose.
2.5.
Clinical examination and scoring
The eyes should be examined at 1, 24, 48 and 72 hours. The grades of ocular reaction
should be recorded. If no evidence of irritation is seen, the study is terminated.
Extended observation may be necessary if there is persistent corneal involvement or
other ocular irritation, for up to 21 days.
3.
DERMAL SENSITISATION STUDY
3.1.
Purpose
The study is used to identify the possible hazard to a population repeatedly exposed to
the test substance.
3.2.
Test substance
The end-use product should be used. Strongly acidic or alkaline substances (pH 2 or
less, or pH 11.5 or greater) might not be tested.
3.3.
Test animals
The young adult guinea pig is the preferred species. The number used depends on the
method employed.
3.4.
Test methods
Any of the following seven test methods would be acceptable. Use of a positive control
substance to test for reliability of the test system is recommended.
51
Appendix 2 (page 3)
Draize Test
Freund’s Complete Adjuvant Test
Mauer Optimisation Test
Buehler Test
Open Epicutaneous Test
Guinea Pig Maximisation Test
Split Adjuvant Technique
4.
ACUTE DELAYED NEUROTOXICITY STUDY
4.1.
Purpose
This screening procedure is for detecting delayed neurotoxic potential of the
test substance.
4.2.
Test animals
The adult domestic laying hen is recommended in sufficient numbers such that
at least six survice the observation period.
4.3.
A preliminary LD50 test should be performed in unprotected hens to establish
the dose levels to be used in this test. The selected dose level should not be
less than the unprotected dose. Doses of test substance higher than 5,000
mg/kg need not be tested.
4.4.
Controls
In addition to an untreated control group, a positive control group should be
used consisting of at least 4 hens treated with a known delayed neurotoxicant,
such as TOCP.
4.5.
Administration of dose
The test substance is preferably administered orally in a single dose by gavage
or using gelatine capsules. After a short while, a protective agent e.g. atropine
should be administered, to prevent death due to cholinergic effects.
52
Appendix 2 (page 4)
4.6.
Observation of animals
All hens should be observed at least once daily up to 21 days after
administration. Signs of toxicity including the time onset should be recorded.
The hens should be subjected to a period of forced motor activity at least twice
a week to enhance the observation of minimal responses. If neurotoxic
responses are not observed or if equivocal responses are seen, then the dose
should be repeated and observations made for another 21 days.
4.7.
Pathology
The examination should be performed on specific nerve tissues such as brain,
spinal cord, terminal peripheral nerves. Sections of the proximal region of the
tibial nerve and its branches should also be taken for examination. Staining of
nervous tissue sections should be made with appropriate myelin or axonspecific stain as well as hematoxylin-eosin stain.
5.
5.1.
SUBCHRONIC ORAL TOXICITY (90-DAY) STUDY
Purpose
This study permits the determination of the no-observed effect level and toxic
effects associated with continous or repeated exposure to a substance for a
period of 90 days. It also provides information on possible health hazards likely
to arise from repeated exposures over a limited period of time.
5.2.
Test animals
At least to mammalian species should be used. The rat and dog are preffered.
Young, healthy animals (at least 10 of each sex) should be used for the rodent
species while 8 (4 of each sex) should be used for the non-rodent species, at
each dose level. If interim sacrifices are planned, the number should be
increased appropriately.
5.3.
Administration
The test substance may be administered in the diet or in capsules. For rodents,
it may be administered by gavage or in the drinking water.
5.4.
At least 3 dose levels and additional control group should be used. This can be
either an untreated group or a vehicle control group. If the toxic properties of
the vehicle is not known, then both untreated and vehicle control groups are
required. The highest dose level in rodents should result in toxic effects but not
produce an incidence of fatalities which would prevent a meaningful evaluation.
For non-rodents, there should be no fatalities.
A satellite group may be treated with the high dose level for 90 days and
observed a further 28 days for reversibility, persistence or delayed occurrence
of toxic effects.
53
Appendix 2 (page 5)
5.5.
Exposure period
The test substance should be administered to the animals, for a period of 90
days. For practical considerations, dosing on a 5-days-per-week basis is
acceptable.
5.6.
Cageside and clinical examinations are required, the former at least once each
day. Clinical examinations should include:
5.6.1. Hematology determinations i.e. hematocrit, hemoglobin concentration,
erythrocyte count, total and differential leukocyte count and a measure
of clotting potential (e.g. clotting time, prothrombin time etc.) These
determinations should be made at the end of the test period for all
survivors. For non-rodents, they should be made at the beginning and
once or twice through the test period as well as at the termination.
5.6.2. Clinical biochemistry determinations on blood e.g. calcium, phosphorus,
sodium, fasting glucose, SGPT, SGOT, urea nitrogen, albumen, blood
creatinine etc. These determinations should be carried out on all
survivors at the end of the test period. For non-rodents, these
examinations should be done once or twice thoughts, these
examinations should be done once or twice through the test period as
well as at the termination.
5.6.3. Urinalysis – only on hight dose and control animals, at the end of the test
period. Tests on appearance, protein, glucose, ketone, occult blood
contents and also microscopy of sediments should be carried out.
5.6.4. Opthalmological examination – only on high dose and control groups, to
be made prior to administration of the test substance and at termination
of study.
5.7.
Pathology
Gross necropsy is required on all animals including those which died or were
found in moribund condition and sacrificed. The major organs should be
weighed i.e. liver, kidneys, adrenals and testes. For non-rodents the thyroid
and parathyroid should also be weighed.
5.8.
Tissue preservation
All gross lesions and certain tissues such as the brain, thyroid, lungs, heart,
bone marrow, liver, salivary glands, kidney, spleen, intestines etc. or their
representative samples should be preserved in a suitable medium.
54
Appendix 2 (page 6)
5.9.
Histopathological examination
Full histopathology should be performed on the organs and tissues mentioned
above, of all rodents in the control and high dose groups, all non-rodents and
all rodents that died or were killed during the study. The examinations should
include all gross lesions and target organs.
In addition certain organs (liver, lungs and kidneys) should also be examined in
the low and intermediate dose groups.
6.
CHRONIC TOXICITY STUDY
6.1.
Purpose
The study is meant to determine the effects of a substance in a mammalian
species following prolonged and repeated exposure. Under the conditions of
this test, effects which require a long latent period or are cumulative should
become manifest.
6.2.
Test animals
Equal numbers of both sexes of at least two mammalian species, a rodent and
non-rodent, should be used, whose characteristics are well-known e.g. rat and
dog. Dosing of rats should begin as soon as possible after weaning, and of
dogs when they are between 4 and 6 months of age.
For rodents it is preferable to perform interim sacrifice, therefore the total
number of animals should be increased appropriately.
6.3.
Generally, the animals should receive the test substance in their diet.
6.4.
At least three dose levels should be used together with a control group. When
the test substance is administered mixed in a vehicle other than food, and the
toxic properties of the said vehicle is unknown, both untreated and vehicle
control groups are required.
6.5.
Exposure period
The duration of the exposure period should be 24 months for rats, 18 months
for mouse and 12 months for dogs.
55
Appendix 2 (page 7)
6.6.
Careful clinical examination should be made at least each week. Records
should be kept of the body weights, food week. Records should be kept of the
body weights, food consumption, sign of toxicity including onset and death; also
time of death.
6.7.
Clinical pathology
If possible, the same animals should be used in the interim examinations.
These include hematology, clinical biochemistry, urinalysis and opthalmological
examinations. At least 10 rodents/sex/dose should be used, and all animals in
the non-rodent group. The examinations should be done at least every 6
months and at study termination.
6.8.
Pathology
Complete gross necropsy should be done on all animals, including those which
died during the experiment or were killed in moribund condition. Specific organs
and tissues should be preserved for possible future histopathological
examination. These include all gross lesions, brain, heart, spleen, uterus,
kidneys, adrenals, muscles, spinal cord, lymph nodes, eyes etc.
6.9.
Histophathological examination
This should be done for all non-rodents. For rodents, all animals in the control,
highest dose group and all those which died or were killed during the study
should be examined. All gross lesions, target organs, lungs, liver and kidneys
should be examined. Examination of organs in the other test group depend on
the organs showing effects in the highest dose group.
7.
7.1.
ONCOGENICITY STUDY
Purpose
In this long-term carcinogenicity study, the purpose is to observe test animals
for a major portion of their life span for the development of neoplastic lesions
during or after exposure to various doses of a test substance by an approptriate
route of administration.
This study may be combined with the chronic toxicity study, if appropriate.
7.2.
Test animals
Equal numbers of both sexes of two mammalian species, preferably rat and
mouse, should be used. Strains that have sufficient historical background data
on spontaneous tumours are preferred. For rodents, at spontaneous tumours
are preferred. For rodents, at least 50 males and 50 females should be used at
each dose level including control. If interim sacrifice is planned, the number
should increase appropriately.
56
Appendix 2 (page 8)
7.3.
In principle, the animals should be given the test substance in their diet.
7.4.
At least three dose levels should be used with a control. This can be either an
untreated group or a vehicle control group. If the toxic properties of the vehicle
is not known, then both untreated and vehicle control group are required.
7.5.
Exposure period
This should comprise the majority of the normal life span of the strain of
animals to be used, e.g. not less than 24 months for rats and 18 months for
mice.
7.6.
Careful clinical observation should be made at least twice each week, where
special attention should be paid to tumour development. Other observations
include body weight and food consumption.
7.7.
Haematology determinations
Blood smears and differential blood count should be obtained from all surviving
animals of the high dose and control groups at 12 and 18 months and also
terminal sacrifice. If relevant, the same samples should be taken from the other
groups.
7.8.
Pathology
Gross necropsy and tissue preservation (as per chronic toxicity study) should
be carried out. In addition, visible tumours and lesions suspected to be
tumorous should be preserved. This also holds for histopathology, where the
examinations to be done are also the same as for the chronic toxicity study.
8.
REPRODUCTION STUDY
8.1.
Purpose
This study is meant to provide general information concerning the effects of the
test substance on reproductive function including estrus cycles, mating
behaviour, conception, parturition, lactation, weaning and growth and
development of offspring. It may also provide information about the effects of
the test substance on neonatal morbidity, mortality and may generate
preliminary data on teratogenesis.
57
Appendix 2 (page 9)
8.2.
Number of generations
Generally, two generations should be treated and observed. For F1, and F2
generations, testing should be performed in the first offspring (first litter) and
the second offspring only where necessary.
8.3.
Test animals
The rat or mouse are the preferred species.
Administration of test substance to parental (P) animals should begin
immediately after weaning. Each test and the control group should contain at
least 20 males and sufficient number of non-pregnant females to yield at least
20 pregnant females at parturition.
8.4.
Dose levels and dose selection
At least three dose levels and a control is required where the highest dose level
should induce toxicity but not mortality in dams. If a vehicle is used in
administering the test substance, the control group should receive the vehicle
in the highest volume used.
8.5.
Experimental schedule
The diagram presented below indicates the experimental schedule for dosing,
mating, parturition and sacrifice.
58
Appendix 2 (page 10)
Experimental Schedule for Test Substance Administration and
Animal Reproduction
Weeks on
Study
P
F1
0
Dosing begins
8-14
11-17
F1 mating
period
F1 born and
litter size
adjusted to 8
pups each.
14-20
Dosing of P
animals ends.
P animals are
sacrificed.
F1 weaned; dosing
or F1 males and
females for
mating begins.
22-34
F1 Offspring not
selected for mating
are sacrificed.
25-37
F1 mating.
F2
F2 born and
litter size
adjusted to
8 pups each
F2 weaned and
F1 (selected for
mating)
are sacrificed.
-----------------------------------------------------------------------------------------------------------(1)
For P generation the males and females should be dosed immediately after
weaning and acclimatizing for at least 1 week. The dosing should be continued
for at least 8 weeks prior to the mating period.
(2)
Dosing of the P generation should continue through the mating period,
pregnancy, lactation and weaning of F1 offspring. P animals should be
sacrificed after weaning of the F2 offspring.
(3)
Dosing of F1 animals saved for mating should begin at the time they are
weaned and continue to the weaning of the F2 offspring. F1 and F2 animals
should be sacrificed after F2 offspring are weaned. (Dosing of F2 animals may
be extended if necessary)
59
8.6.
In principle, the test substance should be administered in the diet. During
pregnancy the dosage may be based on the body weight at Day 0 and 6 of
pregnancy.
8.7.
Mating procedure
For mating the F1 offspring, 1-2 males and 1-2 females are randomly selected
from as many litters as possible to produce the F2 generation. For cross mating
of the F1 offspring, males and females from the same dose group should be
mated avoiding mating of siblings. F1 offspring not selected for mating should
be sacrificed upon weaning.
Each female should be placed with a single male from the same dose group
until mating is confirmed or 3 weeks have passed. Each morning the female
should be examined for vaginal plug, and Day 0 of pregnancy is defined as the
day vaginal plugs or sperm are found. Pairs which fail to mate should be
evaluated to determine the cause of the apparent infertility.
Near parturition, pregnant females should be caged separately in delivery or
maternity cages and provided with nesting materials.
8.8.
Standardization of litter sizes
On Day 4 after birth, the size of each litter should be adjusted by eliminating
extra pups by random selection to yield 4 males and 4 females per litter. If this
is not possible, partial adjustment to 8 animals in total is permitted. However,
adjustments are not appropriate for litters of less than 8 pups.
8.9.
Each animal should be observed at least once daily and pertinent behaviuoral
changes or signs of toxicity recorded. The duration of gestation should be
calculated from day 0 of pregnancy. Each litter should be examined as soon as
possible after delivery for the number of pups, stillbirth, live births and presence
of gross anomalies. From the results of all observations, mating indices,
parturition indices, number of males, impregnated females and viability indices
of weanlings should be calculated.
60
The definitions of these parameters are:
Mating index
=
No. of animals mated x 100
-------------------------------------------------No. of animals used for mating
Pregnancy index
=
No. of pregnant females x 100
-------------------------------------------------No. of males mated
Parturition index
=
No. of females delivering live pups x 100
------------------------------------------------------No. of pregnant females
Viability index at weaning = No. of viable pups at weaning x 100
-------------------------------------------------Adjusted no. of pups at day 4 of birth
8.10. Gross necropsy
When sacrificed, each animal should be examined macroscopically with special
attention to the organs of reproduction, and these organs should be preserved
for histopathological examination.
8.11. Histopathology
Histopathology of the following organs and tissues of all highest dose and
control P and F1 animals selected for mating should be performed : vagina,
uterus, ovaries, testes, epididymus, seminal vesicles, prostrate and pituitary.
Organs demonstrating toxicologically significant abnormalities should then be
examined histopathologically in animals from the other dose groups.
9.
TERATOGENICITY STUDY
9.1.
Purpose
The study us aimed at obtaining information on whether the test substance has
the potential to induce permanent structural or functional abnormalities during
the period of embryonic development.
61
9.2.
Test animals
At least twenty pregnant animals of a suitable species (rat, mice or hamster) or
twelve rabbits should be used at each dose level and control group. The strain
used should be characterized for its response to teratogens.
9.3.
At least three dose levels with a control should be used. In the case of
substance of low toxicity, if a dose level of at least 1000 mg/kg produces no
evidence of embryotoxicity or teratogenicity, studies at other dose levels are
not necessary.
If a vehicle is used, it should not be teratogenic nor have effects on
reproduction. There should then be a vehicle control group.
9.4.
Exposure period
Day 0 of pregnancy is the day on which vaginal plug and/ or sperm is observed.
The dose period should cover the period of major organogenesis, and may be
extended to approximately 1 day before the expected delivery date.
9.5.
Administration
The test substance should be administered orally by gavage at approximately
the same time each day. Allowance must be made for the rapid weight gain
which takes place during pregnancy when deciding the amount to be
administered.
9.6.
The animals should be observed at least once each day and records made of
all observations including signs of toxicity, time of onset, degree, duration; also
food consumption and body weight. Females showing signs of abortion of
premature delivery should be sacrificed and subjected to thorough macroscopic
examination.
9.7.
Teratological examination
At the time of sacrifice or death during the study, the dam should be examined
macroscopically for any structural abnormalities or pathological changes which
may have influenced the pregnancy. Immediately after sacrifice or death, the
uterus should be removed and the contents examined for embryonic or fetal
death in utero where this has occurred. The number of corpora lutea should be
determined, the sex of the fetuses also determined and each litter should be
weighed. The mean fetal weight should be derived.
62
Following removal each fetus should be examined externally for rats, mice and
hamsters, one third to one-half of each litter should be prepared and examined
for skeletal anomalies, and the remaining part of each litter should be prepared
and examined for soft tissue anomalies. For rabbits, each fetus should be
examined by careful dissection for visceral anomalies and then examined for
skeletal anomalies.
10
MUTAGENICITY STUDY
10.1. Purpose
The study is used to determine the ability of the test substance to affect the
integrity of the mammalian cell’s genetic components.
10.2. Basic approach
The battery of studies including the following 3 categories are required:
10.2.1.
Studies to detect gene mutation:
Bacterial Reverse Mutation Assay
Principle of the method: Bacteria are exposed to the test substance both in
the presence and absence of metabolic activation system and plated on
minimal agar medium. After a suitable period of incubation, revertant colonies
are counted and compared to the number of spontaneous revertants in a
solvent control culture. The metabolic activation system stated here is the
method using the mixture (S-9 MIX) of supernatant fraction of the livers of the
animals pre-treated with the agent to induce microsome metabolic enzyme
activity.
Tester strains : Salmonella typhimurium TA100, TA198, TA1535, TA1537 and
other strains, and Escherichia coli WP2 uvr A.
Dose levels : At least 5 dose levels should be used, with the highest level
producing cytotoxic effects. A solvent control, positive control which require S-9
and positive controls which do not require S-9 mix should be used for each unit
of assay.
Number of plates : At least two plates for each dose and control. All plates
should be incubated at 370C for 48-75 hours. At the end of the incubation
period, the number of revertant colonies per plate should be counted.
63
10.2.2.
Studies to detect chromosomal aberration:
Chromosomal aberration – in vitro Mammalian Cytogenetics Test
Principle of the method : Following exposure to the test substance at various
intervals of the cell cycle, cell cultures of established cell lines or primary cell cultures
are treated with colchicines or colcemide and analysed for chromosomal abnormalities
in metaphase cells.
Main requirements : Cell lines which can be used include human cells, Chinese
hamster cells and human lymphocytes. At least 3 dose levels should be employed, the
highest level producing 50% inhibition of growth. A compound known to produce
chromosomal aberration in vitro should be used as the positive control. A solvent and
untreated control should also be included.
A test with metabolic activation system should also be conducted where a compound
known to require activation should be used as the positive control in this case.
Number of cultures : At least 2 cultures should be used for each experimental point.
For established cell lines, cultures should be treated with the test substance when
they are in the exponential stage of growth. Cell cultures are treated with colchicine
prior to harvesting. Each culture is harvested and processed separately for the
preparation of chromosomes. At least 100 well-spread metaphase cells per culture
should be analysed for chromosomal abnormalities.
10.2.3.
Studies to detect genotoxic effects.
Genotoxic effect – Bacterial Repair Test
Principle of the test method : A paper disc containing the test substance is placed
on an agar plate in which bacterial spores are inoculated. The diameter of inhibition
zone is determined 24 hours after treatment. Tests with metabolic activation are also
recommended.
Tester strains : Bacillus subtilis M45 and H 17 can be used.
Other basic requirements : At least 5 dose levels should be tested, the highest level
producing cytotoxic effects. Negative controls such as kanamycin, streptomycin etc.
and positive controls such as AF-2, 2-aminoanthracene etc. should be employed for
each unit of assay. At least one plate should be used for each dose and control level.
64
11.
METABOLIC STUDY
11.1. Purpose
The study is aimed at characterizing the behaviour of the test substance in the
animal body such that this cab be used to evaluate test results from other
toxicology studies and also to extrapolate data of test done on animals to man.
11.2. Test substance
Radiochemically pure grade of the active ingredient in labelled form should be
used.
11.3. Test animals
At least 1 species among rat, dog etc. should be used i.e. young adults. It is
preferable to use the same animal species and strain as those being used for
other toxicological studies.
11.4. Dose level and selection
At least 2 dose levels should be used, the upper dose producing toxic or
pharmacologic signs and the low dose corresponding to a no-effect level.
Where feasible, an additional level approximate to the potential dietary
exposure should also be included.
11.5. Administration
The test substance should be administered in the diet but intravenous means
can also be employed if necessary. Animals should receive a single dose but if
the substance is expected to accumulate in the animal, continous dosing
should be done.
11.6. Procedures
The absorption rate and the rate, ratio and route of elimination should be
determined. Periodical measurement of the test substance concentration in
blood, plasma or serum is required for this. Samples of expired air, urine and
feces should be collected separately from each individual animal in order to
determine the excretion. These measurements should be done several times
and continued until approximately 90% of the administered dose is eliminated,
or for 7 consecutive days.
The distribution of the test substance and other related compounds in major
organs should be determined at different time points. The major metabolites
should be identified, to clarify the major metabolic pathways. The recovery of
the dose in the excreted parent substance and its major metabolites should be
determined at a certain period of time after administration.
65
12.
METABOLISM IN PLANTS
The purpose of this study is to characterize the absorption / translocation of the
test substance via root and foliage system of the plant and the major metabolic
pathways including photochemical reactions of the test substance in the plant
body. Comparison of the plant metabolites with the animal metabolites can be
made combined with the findings from the animal study.
Test plants should preferably be of the crops to be treated with the chemical or
those which are close species to the crops.
Test plants should be treated by a method similar to that of the test chemical.
There are two preferred method-direct application and methods which allow the
plant to absorb the test substance via the root. Absorption, distribution (to
edible part) and metabolism should be determined. Recovery of parent
substance and metabolites in treated and untreated parts should be periodically
determined.
Additional studies include metabolism in the soil and degradation in natural
water, especially if the test substance demonstrates long-term residues in the
soil.
13.
ACUTE FISH TOXICITY STUDY
13.1. Test fish
One or more species may be used, preferably those which are readily available
throughout the year, easily maintained and whose relevant economic, biological
and ecological characteristics are known. They should be acclimatised at least
12 days before the test at temperatures appropriate to the species. Feeding
must be stopped 24 hours before test. All fish must be exposed to water of the
quality to be used in the test for at least 7 days before they are used.
13.2. Preparation of test substance
Stock solutions of the required strength are prepared by dissolving the
appropriate amount of the test substance in the required volume of dilution
water. The chosen test concentrations are prepared by dilution of the stock
solution. The test should be carried out without adjustment of pH. Generally, no
reference substances are required.
66
13.3. Test procedure
The usual procedure is that of the static test where there is no flow of test
solution occurring – solutions may remain unchanged throughout the duration
of the test. Measurements of pH, dissolved oxygen and temperature must be
carried out at least daily.
The fish are exposed to the test substance at a range of concentrations,
preferably for a period of 96 hours. Mortalities are recorded at 24, 48, 72, and
96 hours and the concentrations which kill 50% of the fish (LC50) are
determined where possible. Visible abnormalities e.g. loss of equilibrium,
swimming behaviour etc. should be recorded. The maximum concentration
tested producing no mortality and the minimum concentration tested producing
total mortality should be recorded.
Mortality in the controls should not exceed 10% at the end of the test.
Median lethal concentrations can be calculated using internationally-accepted
standard procedures.
67
Appendix 3 (page 1)
TABLE C: PROTOCOL FOR ACUTE ORAL TOXICITY STUDIES
TEST CONDITIONS
ACUTE ORAL
1. Test substance……… i) If the study using the formulation as the test substance
involves any difficulty, technical material may be used
in lieu of the formulation.
ii) If technical grade of active ingredient is used as the test
substance, it should be of the same composition as that
used for manufacturing the formulation.
2. Test animals…………
2.1. Species…………
2.2. Age……………..
2.3. Sex……………
2.4. Number…………
2.5. Animal status
At least one species of rat
Young adult animals should be used
Both sexes and the female should be non-pregnant
For rodents, 10 animals (5 females + 5 males) for each
dose level
Animals should be fasted prior to the substance
administration: Rat – overnight; other animals with higher
metabolic rates a shorter period fasting is sufficient
i) At least 3 dose levels spaced appropriately to produce in
test group a range of toxic effects and mortality rates.
3. Dose levels…………...
The data should be sufficient to produce a dose
response curve and where possible permit an
acceptable determination of LD50.
ii) If a test at one dose level of at least 5000mg/kg body
weight on not less than 10 rats of equal numbers of
sexes using the procedure described for the study,
produces no compound related mortality, then the full
study using the minimum three dose levels might not be
necessary.
4. Preparation of test
substance…………….
When necessary the test substance should be dissolved
or suspended in water or a suitable vehicle. The toxic
characteristics of the vehicle should be known.
68
Appendix 3 (page 2)
TEST CONDITIONS
ACUTE ORAL
5. Administration of test
substance……………. i) The test substance should be administered in a single
dose by gavage using a tube or suitable intubation
cannula. If a single dose is not possible, the dose may
be given in smaller fractions over a period not
exceeding 24 hours.
ii)
The maximum volume of liquid that can be
administered at one time depends on the size of the
test animal. In rodents, the volume must not exceed 1
ml/100 g body weight.
6. Frequency of
observation…………..
.
7. Observation period…
8. Observation of the
animals……………….
Observations should be made frequently on the first day
of the administration and at least once each subsequent
day.
Should be at least 14 days
i) Cageside observations should include, but not limited to
changes in:
a. The skin & fur
b. Eyes & mucous membranes
c. Respiratory system
d. Circulatory system
e. Autonomic and central nervous system
f. Behavioral pattern
g. Somatomotor activity
h. Particular attention should be directed to
observation of tremors, convulsions salivation,
diarrhea, lethargy, sleep and coma.
ii) Individual weights of animals should be recorded
shortly before the test substance is administered,
weekly thereafter and at death.
iii) The time of death should be recorded as precisely as
possible.
iv) At the end of the test surviving animals should be
weighed and sacrificed.
69
Appendix 3 (page 3)
TEST CONDITIONS
9. Gross pathological
10. Data and reporting
10.1. Treatment of
results…..
10.2. Evaluation of
results…..
10.3. Test report…
ACUTE ORAL
Necropsy of animals should be carried out and all gross
pathological changes should be recorded.
Data shall be summarised in tabular form, showing for
each test group:
i) The number of animals and their body weights at
the start of the test,
ii) Time of death of animals a different dose levels,
iii) Number of animals displaying other signs of
toxicity,
iv) Description of toxic effects, and
v) Necropsy findings
An evaluation of results should include the relationship, if
any, between the dose of the test substance and the
incidence, severity and reversibility of all abnormalities,
including behavioral and clinical effects, gross lesions,
body weight changes, effects on mortality, other
toxicological effects.
The test report should include the following
information:
i) Species/strain/source used; diet, environmental
conditions,
ii) Tabulation of response date by sex and dose level (i.e.
number of animals exposed, number of animals
showing signs of toxicity; number of animals which
died or were killed during the test),
iii) Description of toxic effects
iv) Dose response curves, for mortality and other toxic
effects (when permitted by the method determination),
v) LD50 values for each sex, determined at 14 days (with
method of determination specified)
vi) 95 percent confidence interval for the LD50
vii) Time of death after dosing
viii) Body weight data
ix) Gross pathological findings.
70
Appendix 3 (page 4)
TEST CONDITIONS
10.4. Statement of
compliance..
ACUTE ORAL
The report should also include statement of compliance
signed by the study director that the test had been carried
out in compliance with Good Laboratory Practice
standards.
71
Appendix 3 (page 5)
TABLE D: PROTOCOL FOR ACUTE DERMAL TOXICITY STUDIES
TEST CONDITIONS
1. Test substance……..
ACUTE ORAL
i) If the study using the formulation as the test substance
involves any difficulty, technical material may be used in
lieu of the formulation
ii) If technical grade of active ingredient is used as the
test substance, it should be of the same composition as
that used for manufacturing the formulation.
2. Test animals……..
2.1. Species……..
2.2. Age……………..
2.3. Sex…………….
2.4. Number………..
At least one species of rat
Young adult animals should be used
Both sexes and the female should be non-pregnant
For rodents, 10 animals (5 females + 5 males) for each
dose level.
Fasting not required
2.5. Animals status…
3. Dose levels……..
4. Preparation of test
substance…………….
i) At least 3 dose levels spaced appropriately to produce
test group with a range of toxic effects and mortality rates.
The data should be sufficient to produce a dose response
curve and where possible permit an acceptable
determination of LD50.
ii) If a test at one dose level of at least 2000mg/kg body
weight on not less than 10 rats of equal numbers of sexes
using the procedures described for the study. Produces
no compound related mortality, then the full study using
the minimum three dose levels might not be necessary.
When necessary the test substance should be dissolved
or suspended in water or a suitable vehicle. The toxic
characteristics of the vehicle should be known.
72
Appendix 3 (page 6)
TEST CONDITIONS
5. Administration of test
substance…………..
6. Frequency of
observation………….
ACUTE ORAL
i) Approximately 24 hours before the test, fur
should be removed from the dorsal area of the
trunk of the test animals by clipping or shaving.
Care should be taken to avoid abrading the skin
which could alter its permeability.
ii) Not less than 10 percent of the body surface are
should be clear for the application of test
substance.
iii) When testing solids, which may be pulverised if
appropriate, the test substance should be
moistened with water or where necessary, a
suitable vehicle to ensure good contact with the
skin. When vehicle is used, the influence of the
vehicle on penetration of the skin by the test
substance should be taken into account.
iv) The test substance should be applied uniformly
over an area approximately 10 percent of the total
body surface.
v) The test substance should be held in contact with
the skin with a porous gauze dressing and nonirritating tape for 24 hours. The test site should be
further covered in a suitable manner to retain the
gauze dressing and the test substance and to
ensure that the animals cannot ingest the test
substance.
vi) At the end of the exposure period, residual test
substance should be removed, where practicable
using water or an appropriate solvent.
Observations should be made frequently on the first
day of the administration and at least once each
subsequent day.
7. Observation period… Should be at least 14 days
8. Observation the
animals………………
i)
Cageside observations should include, but not
limited to changes in:
a. The skin & fur
b. Eyes & mucous membranes
c. Respiratory system
e. Circulatory system
73
Appendix 3 (page 7)
TEST CONDITIONS
ACUTE ORAL
e. Autonomic and central nervous system
f. Behavioral pattern
g. Somatomotor activity
h. Particular attention should be directed to
observation of tremors, convulsions, salivation,
diarrhea, lethargy, sleep and coma.
ii) Individual weights of animals should be recorded
shortly before the test substance is administered,
weekly there after and at death.
iii) The time of death should be recorded as precisely as
possible.
iv) At the end of the test surviving animals should be
weighed and sacrificed.
9. Gross pathological.
10. Data and reporting.
10.1. Treatment of
results…..
10.2. Evaluation of
results…….
10.3. Test report…..
Necropsy of animals should be carried out and all gross
pathological changes should be recorded.
Data shall be summarised in tabular form, showing for
each test group:
i)
The number of animals and their body weights
at the start of the test,
ii)
Time of death of animals at different dose
levels,
iii)
Number of animals displaying other signs of
toxicity,
iv)
Description of toxic effects, and
v)
Necropsy findings.
An evaluation of results should include the relationship, if
any, between the dose of the test substance and the
incidence, severity and reversibility of all abnormalities,
including behavioral and clinical effects, gross lesions,
body weight changes, effects on mortality, other
toxicological effects.
The test report should include the following information:
i)
Species/strain/source used; diet, environmental
conditions,
74
Appendix 3 (page 8)
TEST CONDITIONS
ACUTE ORAL
ii)
iii)
iv)
v)
vi)
vii)
viii)
ix)
10.4. Statement of
compliance…
Tabulation of response data by sex and dose level
(i.e. number of animals exposed, number of
animals showing signs of toxicity; number of
animals which died or were killed during the test),
Description of toxic effects
Dose response curves, for mortality and other toxic
effects (when permitted by the method of
determination)
LD50 values for each sex, determined at 14 days
(with method of determination specified)
95 percent confidence interval for the LD50
Time of death after dosing
Body weight data
Gross pathological findings.
The report should also include statement of compliance
signed by the study director that the test had been carried
out in compliance with Good Laboratory Practice
standards.
75
GP 3/93
GUIDELINES ON
EFFICACY DATA REQUIREMENTS
FOR
Pesticides Board
Malaysia
2009
76
Efficacy Data Requirement for
__________________________________________________
Substantiation of claims made on the efficacy of a product submitted for registration is
a requirement under the Pesticides Act 1974. To assist applicants in their submission
for registration, the following additional guidelines have been prepared. Applicants are
advised to follow the harmonised protocols developed under the FAO through its
Regional Project on the Implementation of the Code of Conduct on the Distribution
and Use of Pesticides (GCP/ITN/456/JPN). Appendix 1 shows the protocols presently
available. In cases where there are no harmonised protocols, applicants are advised
to use the following general guidelines.
A.
GENERAL REQUIREMENTS
1.
For all proprietary pesticides recommended to be used on major crops i.e. rice,
oil palm, cocoa, and rubber, efficacy evaluation results obtained from local verification
trials is required. For other crops, result(s) obtained from trials conducted in other
countries under similar climatic regime and cultural practice may be considered.
2.
For commodity products efficacy data is not required if label claim is similar to
that shown in the “Approved Uses for Commodity Pesticides”, document number
GP5/93. Any other additional claim(s) must be substantiated with data.
B.
GUIDELINES FOR EFFICACY EVALUATION OF INSECTICIDES
USED IN AGRICULTURE.
10.
Experimental Conditions
a.
Selection of crop and cultivar, test organisms – The selection of crop,
cultivar, and insects must be relevant to the (proposed) label claims.
b.
Trial Conditions – Trials should be conducted only on crops with known
history of uniform high infestation of the targeted pest(s). Cultural conditions e.g. soil
type, fertilizers, tillage, row spacing etc. should be uniform for all plots of the trial and
should conform with local agricultural practices. The timing, amount and method of
irrigation, if applied, should be recorded. Trials should be carried out in different
regions with distinct environmental conditions and preferably in different planting
seasons (where applicable).
c.
Treatments – Test product(s), reference product(s) and untreated control,
arranged in a randomized block or any other statistically suitable design.
d.
Plot size and replication – Net plot size: at least 15 square meters or 25
plants depending on type of plants, formulation of insecticides, and type of equipment
to be used in applying the insecticides.
Replicates: at least three, provided the error degrees of freedom are at least 12.
77
11.
2.1
Application of Treatments
Test Product(s) – The formulated product under investigation.
2.2
Reference Product(s) – Registered product known to be satisfactory for the
control of the insect pest(s) under investigation. In general, formulation, type and
mode of action should be close to those of the test product(s).
2.3
Mode of Application – Application should comply with good agricultural
practice.
2.4
Type of Application – as specified on the (proposed) label.
2.5
Type of equipment used – should be of a type in current use .It should
provide an even distribution of product on the whole plot or accurate directional
application where appropriate. Factors which may affect efficacy (such as operating
pressure, nozzle type, depth of incorporation) should be recorded, together with any
deviations in dosage of more than 10%.
Precaution should be taken to avoid drift between plots.
2.6
Time and frequency of application – The time and frequency of application
will normaly be specified on the (proposed) label. The number of application and the
date of each application should be recorded.
2.7
Doses and volumes used – According to instructions on the (proposed) label.
The products should be tested at the recommended dose and may also usefully be
tested at other doses. The dosage will normally be expressed in kg or 1 of formulated
product per ha. It may also be useful to record the dose in g of active ingredient per
ha. For sprays, data on concentration (%) and volume (1/ha) should also be given.
2.8
Data on chemicals used against other pests – If other chemicals have to be
used, they should be applied uniformly to all plots, separately from test product(s) and
reference product(s). Possible interference with these should be kept to a minimum.
Precise data on the applications should be given.
12.
Assessment, Recording and Measurements
3.1
Meteorological and edaphic data – On the date of application, meteorological
data which are likely to affect the quality and persistence of the treatment should be
recorded. This normally includes at least precipitation (type and amount in mm) and
temperature (average, maximum, minimum in oC) Any significant change in weather
should be noted, and in particular its time relative to the time of treatment. Around the
date of application, meteorological data should be recorded which are likely to affect
the development of the crop and/ or pests and the action of the insecticide.
Throughout the trial period, extreme weather conditions, such as severe or
prolonged drought, heavy rain, hail etc., which are likely to influence the results,
should be reported.
78
3.2
Edaphic data – Depth of water layer, over-flowing water or drainage,
excessive algal growth or excessive organic matter content of water or soil should be
recorded.
3.3
Type, time and frequency of assessment – Type of assessment depends on
the type of pest(s) but normally by number of insects on all plants in the trial.
Preliminary assessment is done immediately before treatment; first assessment 1-3
days after treatment; second assessment 7 – 14 days after treatment. If long-term
effects are claimed, further assessments at 14 days intervals should be carried out.
3.4
Direct effects on the crop – The crop should be examined for presence or
absence of phytotoxic effects. The type and extent of these should be recorded. In
addition, any positive effects should be noted.
Phytotoxicity is recorded as follows:
(a)
if the effect can be counted or measured, it may be expressed in
absolute figures;
(b)
in other cases, the frequency and intensity of damage may be estimated.
This may be done in either of two ways: each plot is scored for
phytotoxicity by reference to a scale which should be recorded; or each
treated plot is compared with an untreated plot and % phytotoxicity
estimated.
In all cases, symptoms of damage to the crop should be accurately described
(stunting, chlorosis, deformation, etc.). Should symptoms of phytotoxicity be detected,
a more detailed assessment should be carried out following the FAO Guidelines for
Phytotoxicity Assessment (FAO/AP/027).
3.5
Effects on other pests – Any effects, positive or negative, on the incidence of
other pests should be noted.
3.6
Effects on other non-target organisms – Any observed environmental effects
should also be recorded, especially effects on wildlife and/or beneficial
organisms. Any observed effects on human safety should also be recorded.
3.7
Quantitative and/ or qualitative recording of yield – Quantitative yield
recording is not required, but any effects on the quality of the product should be
noted (e.g. marketability of produce).
4.
Results
4.1
The results should be reported in a systematic form and the report should
include an analysis and evaluation. Original (raw) data should be available. Statistical
analysis should be used, where appropriate, by methods which should be indicated.
For further details, refer to Appendix 2.
79
C.
GUIDELINES
FOR EFFICACY
FUNGICIDES USED IN AGRICULTURE.
1.
EVALUATION
OF
1.1. Selection of crop and cultivar, test organisms – The selection of crop,
cultivar, and pathogens must be relevant to the proposed label claims.
1.2. Trial Conditions – Trials should be conducted only on crops with known
history of uniform high infestation of the target diseases. Cultural conditions e.g. soil
type, fertilizers, tillage, row spacing etc. should be uniform for all plots of the trial and
should conform with local agricultural practices. The timing, amount and method of
irrigation, if applied, should be recorded. Trials should be carried out in different
regions with distinct environmental conditions and preferably in different planting
seasons where applicable.
1.3. Treatments – Test product(s), reference product(s) and untreated control,
arranged in a randomized block or any other statistically suitable design.
1.4
Plot size and replication – Net plot size: for tree crops such as oil palm,
rubber, cocoa and citrus at least 4 trees depending on type of plants, diseases,
formulation of fungicides, and type of equipment to be used in applying the fungicides.
Replicates: at least three, provided the error degrees of freedom are at least
2.
2.1
Test Product(s) – The formulated products under investigation.
2.2. Reference Product(s) – Registered product known to be satisfactory for the
control of the disease(s) under investigation. In general, formulation, type and mode of
action should be close to those of the test product(s).
2.3
Mode of Application – Application should comply with good agricultural
practice.
2.4
Type of application – As specified on the (proposed) label.
2.5
Type of equipment used – should be of a type in current use. It should
provide an even distribution of product on the whole plot or accurate directional
application where appropriate. Factors which may affect efficacy (such as operating
pressure, nozzle type) should be recorded, together with any deviations in dosage of
more than 10%.
2.6
Time and frequency of application – The time and frequency of application
should correspond to that specified on the (proposed) label. The number of application
and the date of each application should be recorded.
80
2.7
Doses and volumes used – According to instructions on the
(proposed) label. The product should be tested at the recommended dose and may
also usefully be tested at other doses. The dosage will normally be expressed in kg or
1 of formulated product per ha. It may also be useful to record the dose in g of active
ingredient per ha. For sprays, data on concentration (%) and volume (1/ha) should
also be given.
2.8
3.
3.1
data should be recorded which are likely to affect the quality and persistence of the
treatment. This normally includes at least precipitation (type and amount in mm) and
temperature (average, maximum, minimum in oC). Any significant change in weather
the development of the crop and/ or disease(s) and the action of the fungicide.
Throughout the trial period, extreme weather conditions, such as severe or
prolonged drought, heavy rain, hail etc., which are likely to influence the results,
should be reported.
3.2
Edaphic data – Depth of water layer, over-flowing water or drainage,
excessive algal growth or excessive organic matter content of water or soil should be
recorded.
3.3
Type, time and frequency of assessment – Type of assessment depends on
the disease(s) under investigation but normally by % infestation per unit area of plant
parts on all plants in the trial. A practical scale for assessment should be used.
Preliminary assessment is done immediately before treatment;
1st assessment – 1 to 3 days after treatment;
2nd assessment – 7 to 14 days after treatment;
If long-term effects are claimed, further assessments at 14 days intervals
should be carried out.
For diseases which are long term such as root diseases, the symptoms of
infestation on the whole tree e.g. wiltering, crown collapse etc. can be taken.
3.4
Direct effects on the crop – The crop should be examined for presence or
absence of phytotoxic effects. The type and extent of these should be recorded. In
addition, any positive effects should be noted.
(a)
absolute figures;
(b)
81
treated plot is compared
with an untreated plot and
% phytotoxicity estimated.
(stunting, chlorosis, deformation, etc.) Should symptoms of phytotoxicity be detected,
3.5
Effects on other pests – Any effects, positive or negative, on the incidence of
other pests should be noted.
3.6
Effects on other non-target organisms – Any observed environmental effects
should also be recorded, especially effects on wildlife and/or beneficial organisms.
Any observed effects on human safety should also be recorded.
3.7
Quantitative and/or qualitative recording of yield – Quantitative yield
recording is not required, but any effects on the quality of the product should be noted
(e.g. marketability or produce).
4.
Results
4.1
D.
GUIDELINES FOR EFFICACY EVALUATION OF HERBICIDES
1.
The biological evaluation of a herbicide involves a programme of trials for
assessment of efficacy in weed control and of selectivity to the crop (crop safety).
Trials may be used either for evaluating weed control or crop safety according to weed
occurrence, provided the conditions specified in the test protocol are satisfied.
2.
2.1
Selection of crop, cultivar and weeds – The selection of crop, cultivar, and
weeds must be relevant to the (proposed) label claims. Consideration with regard to
crop safety may also be given to cover crops, where applicable, which may be sown
together with the primary crop. If crop safety of more than one cultivar needs to be
tested, special varietal trials should be carried out.
2.2
Evaluation of efficacy in weed control – The plots should be known to carry
a varied but uniform weed population. The weed population should correspond to the
specific action spectrum of the herbicide to be tested (e.g. grasses, sedges and/or
broadleaf weeds, annuals and/or perennials).
82
2.3
Evaluation of crop safety – The plots should preferably be as free from
weeds as possible. Other herbicides should not be used, unless one is certain that
they have no effect on the crop and do not interact with the test product(s) or
reference product(s). If any weeds remain, they should preferably removed by hand or
mechanically.
2.4
Trial Conditions – Cultural conditions e.g. soil type, fertilizers, tillage, row
spacing etc. should be uniform for all plots of the trial and should conform with local
agricultural practices. The timing, amount and method of irrigation, if applied, should
be recorded. Trials should be carried out in different regions with distinct
environmental conditions and preferably in different planting seasons where
applicable.
2.5
Treatments – The product(s) and reference product(s) at individual doses
and/or application times, and untreated control(s), arranged in a randomized block or
any other statistically suitable design.
2.6
Plot size and replication – Net plot size: at least 10 meter square depending
on type of plants, mode of application of the herbicide(s), and type of equipment to be
used in applying the herbicide(s). For crop safety tests the net plot size should be at
least 4 plants. Depending on the type of application, actual plot size may have to be
larger than net plot size in order to take account of possible drift.
Replicates: at least three, provided the error degrees of freedom are at least
12.
3.
3.1
Test Product(s) – The formulated product under investigation.
3.2
Reference Product(s) – Registered product(s) known to be satisfactory for the
control of the weed types under investigation. In general formulation type and mode of
action should be close to those of the test product(s)
3.3
Mode of Application – Application should conform with good agricultural
practice.
3.4
Type of application – The type of application as specified on the (proposed)
label.
3.5
Type of equipment used – The equipment should be of a type in current use.
It should provide an even distribution of product(s) on the whole plot or accurate
directional application where appropriate. Factors which may affect efficacy and/or
duration of weed control and/or crop safety (such as operating pressure, nozzle type,
depth of incorporation) should be recorded, together with any deviations on dosage of
more than 10%.
83
3.6
Time
and
frequency
of application – The time and frequency of
application should correspond to that specified on the (proposed) label. Application
times should be related to the emergence of the crop and of the weeds. The same
product may be applied once or in follow up application.
The number of applications and the date of each application should be recorded.
3.7
The product(s) should be tested at the recommended dose and may also usefully be
tested at other doses. The dosage will normally be expressed in kg or 1 of formulated
product per ha. It may also be useful to record the dose in g of active ingredient per
ha. For sprays, data on concentration (%) and volume (1/ha) should also be given.
3.8
4.
4.1
data should be recorded which are likely to effect the quality and persistence of the
treatment. This normally includes at least precipitation (type and amount in mm) and
temperature (average, maximum, minimum in oC). Any significant change in weather
the development of the crop and/or weeds and the action of the herbicides.
Throughout the trial period, extreme weather conditions, such as severe or prolonged
drought, heavy rain, hail etc., which are likely to influence the results, should be
reported.
4.2
Edaphic data – The following characteristics of the of the soil should be
recorded: pH, organic matter content, soil type (according to a specified national or
international standard), moisture (e.g. dry, wet, waterlogged), seed bed quality (tilth)
and fertilizer regime.
4.3
Observation on weeds – The weed population of a plot can be recorded in
terms of numbers, cover or mass (normally dry weight). These may be assessed in
absolute terms and/or estimated.
4.3.1 Absolute assessment
Individual plants may be counted for each weed species or the mass of each
species may be determined by weighing (normally dry weight). These assessments
can be made on whole plots or on randomly selected marked quadrats (up to 1 m sq.)
in each plot. In certain cases, it may be preferable to count or measure particular plant
organs (e.g. flowering or fruiting tillers in weeds).
84
4.3.2 Estimation
Each treated plot is compared with an adjacent untreated plot or control strip,
and the relative weed population is estimated. The assessment involves a general
estimation of the total weed population or of individual weed species, combining in
one figure an estimate of number, cover, height and vigour (i.e. virtually weed
volume). It is in principle rapid and simple. The result may be expressed simply as a
percentage (i.e. on a linear scale from 0 = no weeds to 100 = same weed infestation
as untreated). An equivalent inverted scale may be used to express percent weed
control (0 = no weed control, 100 = full weed control). Information should also be
provided on the absolute level of weed infestation in the untreated plots or strips
(absolute assessment of weed cover). In order to describe exactly the mode of action
of the product, symptoms of damage to the weeds should be accurately described
(stunting, chlorosis, deformation, etc.).
Effects on weeds can usefully be noted over 2 seasons. This is essential for
deep rooted or difficult weeds (such as Cyperus rotundus, Imperata cylindrical) as
they may not be killed and might reappear the following year.
4.4
Observation on the crop – Phytotoxicity is evaluated primarily on crop safety
plots which are also harvested. However, the type and extent of damage to the crop
should be recorded on efficacy plots and may provide useful additional information.
(a)
absolute figures;
(b)
treated plot is compared with an untreated plot and % phytotoxicity
estimated.
(stunting, chlorosis, deformation, etc.). Should symptoms of phytotoxicity be detected,
4.5
Observation on side-effects – Any effects on non-target organisms should be
recorded.
4.6
Time and frequency – The times given apply to weed control and crop safety
assessment, unless otherwise indicated. Frequency of assessment should cover
possibility of regrowth.
(a)
(b)
Pre-emergence applications:
1st assessment –
when approximately 90 % of the crop has
emerged in the untreated plot.
2nd assessment –
20 to 30 days after treatment.
3rd assessment –
60 days after application.
th
4 assessment –
before harvest.
Post-emergence applications:
1st assessment (preliminary)
–
on the day of treatment,
the weed and crop cover in each
85
plot should be recorded.
2nd assessment (weed control only) –
3rd assessment –
4th assessment –
th
5 assessment –
before harvest.
4.7
Quantitative and/ or qualitative recording of yield – For crop safety testing
and weed control testing harvesting is optional in most cases.
5.
Results
5.1
include an analysis and evaluation.
Original (raw) data should be available. Statistical analysis should be used, where
appropriate, by methods which should be indicated. For further details, refer to
Appendix 2.
E.
GUIDELINES FOR BIOLOGICAL EVALUATIONS
INSECTICIDE PRODUCTS IN THE LABORATORY
1.
OF
HOUSEHOLD
1.1
Equipments and test organisms – A transparent glass chamber or Peet
Grady chamber (between 70 x 70 x 70cm to 180 x 180 x 180cm) and laboratorycultured adult insects of known age group (eg. sucrose-fed female mosquitoes aged 2
– 5 days) should be used. In case of mosquitoes Aedes aegypti or Culex
quinquefasciatus, being easily available, are the preferred species.
1.2
Treatments and Replicates – Test product(s) and reference product(s) should
be tested and replicated at least three times.
2.
2.1
Test Product(s) – The formulated product(s) under investigation.
2.2
Reference Product(s) – Registered product(s) known to be satisfactory for the
control of the household insect pest(s) under investigation.
2.3
Mode of Application – Application method should correspond to the method
proposed on the label.
2.4
Type of equipment used – should be of a type in current use. It should
provide an even distribution of product in the test chamber.
2.5
The product should be tested at the recommended dose and at other doses where
appropriate.
86
3.
Assessment and Recording.
3.1
Type, time and frequency of assessment – Assessment should be by
number of insects knocked down observed at indicated intervals up to 20 minutes.
Mortality after 24 hours posttreatment should be recorded.
4.
Results
4.1
5.
General
5.1
Applicants are advised to follow the test methods stated in the following
documents.
(a)
(b)
(c)
(d)
(e)
(f)
(g)
(h)
Glass Chamber Method for testing mosquito coils (SIRIM MS 23);
Peet Grady Chamber Method for testing mosquito coils
Glass Chamber Method for testing mosquito mats (SIRIM MS 1044);
Peet Grady Chamber Method for testing mosquito mats;
Glass Chamber Method for testing of aerosols against mosquitoes
(SIRIM MS 1186);
Peet Grady Chamber Method for testing of aerosols against mosquitoes;
Glass Cylinder Method for testing of aerosols on cockroaches (SIRIM
MS 1100);
Residual tests on polywood plate/ cement block for cockroaches (SIRIM
MS 1130);
In cases where there are no test methods specified applicants are advised to use the
above guidelines.
87
Appendix 1
LIST OF HAMONISED BIOEFFICACY PROTOCOLS
FAO/AP/001
FAO/AP/002
FAO/AP/003
FAO/AP/004
FAO/AP/005
-
FAO/AP/006
FAO/AP/007
FAO/AP/008
FAO/AP/009
FAO/AP/010
FAO/AP/011
FAO/AP/012
FAO/AP/013
FAO/AP/014
FAO/AP/015
FAO/AP/016
FAO/AP/017
FAO/AP/018
FAO/AP/019
FAO/AP/020
FAO/AP/021
FAO/AP/022
FAO/AP/023
FAO/AP/024
FAO/AP/025
FAO/AP/026
FAO/AP/027
FAO/AP/028
FAO/AP/029
FAO/AP/030
FAO/AP/031
FAO/AP/032
FAO/AP/033
FAO/AP/034
FAO/AP/035
FAO/AP/036
FAO/AP/037
FAO/AP/038
FAO/AP/039
FAO/AP/040
-
Planthoppers on Rice
Stemborers on Rice
Leafhoppers on Rice
Plutella xylostella
Alternaria solani and Phytophthora infestans on
tomato
Phytophthora infestans on Potato.
Weeds in Rice.
Weeds in Sugarcane.
Weeds in Maize.
Weeds in Banana.
Seed Bugs on Rice.
Rice Water Weevil.
Leaf Folders on Rice.
Sheath Blight of Rice.
Blast Disease of Rice.
Mites on Citrus.
Scale Insects on Citrus.
Heliothis armigera on Citrus.
Citrus Leafminer.
Webworm and Heartworm on Cabbage.
Anthracnose of Capsicum spp.
Corn Borers on Maize.
Bollworms on Cotton.
Rice Hispa.
Apple Scab.
Armyworms on Maize.
Guidelines for Phytotoxicity Assessment.
Sucking Insect Pests of Cotton.
Mites on Apple.
Aphids on Apple.
Whorl Maggots on Rice.
Black Bugs on Rice.
Weeds on Oil Palm and Rubber.
Weeds on Phaseolus, Pisum and Vigna.
Blue Mould of Tobacco.
Fruit Flies on Cucurbits.
Hoppers on Mango.
Fruit Flies on Mango.
Codling Moth on Apple.
Numerical Code for the Growth Stages of the Rice Plant.
88
Appendix 2
GUIDELINES FOR REPORTING OF EFFICACY EVALUATION
It is essential that the presentation of the results should be standardized in
order to facilitate understanding of the trial results. Therefore, the data should
preferably be presented in the following way:
-
name of the experimenter and organization responsible for the trial;
objective and location of the trial;
chemical name and formulation;
insect pest, disease or weed against which tested;
crops and cultivars;
plant growth stage;
soil type;
experimental design, size and number of plots treated;
application dates and rates;
application method and equipment;
volume of spray liquid or other carrier types;
weather conditions during and after treatment;
treatment of the plots with other crop protecting materials, fertilizers and
other products;
application dates;
dates of assessment;
size and frequency of sampling;
quantity and quality of yield of the harvested crop where required;
any results on crop safety including intervals to be observed in order to
avoid phytotoxic effects;
data assessment including significance;
interpretation and discussion on the results of the experiment in comparison
with similar trials.
89
Appendix 3
GUIDELINES FOR REPORTING OF LABORATORY
BIOLOGICAL EVALUATIONS OF HOUSEHOLD INSECTICIDE PRODUCTS
The data obtained from laboratory evaluations of household insecticide
products should preferably be presented in the following manner:
-
name of the experimenter and organization responsible for the test(s);
objective of the test(s);
chemical name and formulation;
insect pest(s) against which tested;
sample size and number of replicates tested;
evaluation dates and rates;
evaluation method and equipment;
volume of spray and/ or duration of exposure of test insects;
dates of assessment;
data assessment including significance;
interpretation and discussion on the results of the test(s).
90
GP4/2012
GUIDELINES ON RESIDUE DATA
REQUIREMENTS FOR PESTICIDE
REGISTRATION
Pesticide Board
Malaysia
2012
91
GLOSSARY
pesticide residue
MRL
PHI
PSI
proprietary products
commodity products
new recommendations
supervised residue trials
local conditions
ADI
NOAEL
"Pesticide residue" means any specified substances in
food, agricultural commodities, or animal feed resulting
from the use of a pesticide. The term includes any
derivatives of a pesticide, such as conversion products,
metabolites, reaction products, and impurities considered
to be of toxicological significance. (Note: The term
"pesticide residue" includes residues from unknown or
unavoidable sources (e.g., environmental), as well as
known uses of the chemical).
Maximum Residue Limit
"MRL" is the maximum concentration of a pesticide residue
(expressed as mg/kg), recommended to be legally
permitted in or in food commodities and animal feeds.
MRLs are based on GAP data and commodities that
comply with the respective MRLs are intended to be
toxicologically acceptable
Pre Harvest Interval
“Pre Harvest Interval” is the time interval between the last
pesticide application and harvest of the treated crops.
Pre Slaughter Interval
“Pre Slaughter Interval” is the time interval between the
last pesticide application and slaughter of the treated
animal.
Any pesticide registered in Malaysia less than ten years
Any pesticide which is not a proprietary pesticide
New crop recommended for any commodity pesticide
Residue trial designed in line with the requirements stated
in ‘Supervised Residue Trials in Crops and Plant Products,
part 3 of ‘FAO/WHO Codex Alimentarius Commission
Guidelines on Producing Residues Data from Supervised
Trials, 1990’.
Local agriculture conditions that follow national GAP, which
include weather, rainfall broadcast and climatic changes.
Acceptable Daily Intake
"ADI" of a chemical is the daily intake which, during an
entire lifetime, appears to be without appreciable risk to the
health of the consumer on the basis of all the known facts
at the time of the evaluation of the chemical. It is
expressed in milligrams of the chemical per kilogram of
body weight.
No Adverse Effects Level
“No Adverse Effects Level” is the highest level of continual
exposure to a chemical which causes no significant
adverse effect on morphology, biochemistry, functional
capacity, growth, development or life span of individuals of
the target species which may be animal or human
92
Limit of Determination
pre-mixture product
subsequent
product
field experiments
in
"Limit
of determination" is the lowest concentration
of a pesticide residue or contaminant that can be identified
and quantitatively measured in a specified food,
agricultural commodity, or animal feed with an acceptable
degree of certainty by a regulatory method of analysis.
Combination of an authorised pre-mix and one or more
active ingredient which are intended for the
manufacture of a ready to use crop protection
Experiment, research or trial conducted under actual
use condition, instead of other controlled condition
the laboratory.
93
Guidelines On
Residue Data Requirements
For Pesticide Registration
A.
INTRODUCTION
Residue data is required for registration of pesticides in order to:
(a) ensure that any residue of pesticides at the time of harvest
does not exceed the maximum residue limits (MRLs), or in the
absence of MRLs, either to enable MRLs to be established or
to establish that MRLs are not necessary;
(b)
recommend a suitable waiting period between the last
application and harvest/slaughter (pre-harvest interval, PHI/
pre-slaughter interval, PSI) or consumption of the commodity
so that residues of pesticides would not exceed MRLs or in
the absence of MRLs, are at levels which would not be of
concern to human and animal health, and
(c)
ensure that a workable method is available to analyze for
pesticide residues in food and/ or in the environment.
B.
REQUIREMENTS
The following requirements must be submitted:
1.
For all products, a proposed label with clear instructions on how
the pesticide is to be used. This is to enable correlation of the
proposed use patterns with the method of application used in
obtaining the residue data. The following must be clearly stated:
(a)
The target crop, stored product or livestock.
(b)
The method of application. This includes information on the
equipment used, dosage (expressed as unit a.i. per unit
area/volume), number of applications, timing of applications,
etc.;
(c)
The stage of growth of the crop or the livestock when the
pesticide is applied, if applicable; and
94
(d)
The recommended PHI,
PSI,
re-entry
aeration period and other observations and limitations.
time,
2.
For proprietary products only, information on the physical,
chemical and biological properties of the pesticide, nature and
amounts of isomers, impurities and by-products which may be
present in the technical or formulated products.
3.
For proprietary products only, information on the behavior and
metabolism/ degradation of the pesticide in crops and plant/
animal products and soil and the nature of the residues as well
as its degradability as indicated by its half-life (t½) in soil and
water at 25o C and its mobility in soils as indicated by adsorption
studies. The metabolism studies are to characterize the residues,
usually by employing radio-labeled compounds. Information on
the amount of bound residues in soil and plants and their bioavailability may also be requested. For studies with livestock, the
study should indicate the distribution of residues in tissues, milk
or eggs and whether the residues are accumulated in any part of
the animal.
4.
For proprietary products, and commodity products with new
recommendations, detailed reports on supervised residue trials.
Trials must be carried out on the recommended crops, livestock
and stored products with the pesticides applied in the same
manner as in the proposed label. In addition to the proposed
label rates, an exaggerated rate (usually 2 times the proposed
rate) should be studied. Studies should preferably be conducted
under local conditions or in locations with similar conditions.
5.
In addition the design and implementation of supervised residue
trials should follow proposed critical Good Agriculture Practice
(GAP) (maximum number of applications, timing of application(s)
at the latest stage permitted within application scope, maximum
application rate, minimum PHI/PSI), which would likely result in
maximum residue. Other factors such as weather condition and
agronomic/husbandry practice should also be considered when
designing supervised residue trials.
6.
For proprietary products and commodity products with new
recommendations, a method of analysis for residues of the
pesticide in the relevant matrix. For pesticides not used on food
or on animals for consumption, a method of analysis for residues
in the environment is required. The method can be a company
95
method or a published method for which the source must
be given. For methods to be accepted, the % recovery must be
within the range of 70%-120%. If 70%-120% recovery is not
attainable, methods having lower recoveries may be accepted if
consistency can be shown. The recovery tests should be at
levels found in practice and actual analysis of treated samples.
Evidence on the workability, reproducibility, selectivity and
sensitivity of the method must be submitted.
7.
Information on MRL enforcement method (or known as postregistration method) should also be provided if possible. MRL
enforcement method is usually in the form of multi-residue
method used by regulatory authorities in enforcement of MRLs.
Single-residue method may not be suitable for MRL enforcement
as enforcement laboratories do not have sufficient capacity to
perform single-residue methods on all pesticides. However
certain active ingredients may not be suitable to be detected by
enforcement method. Registrant should consult the Pesticide
Board for possible establishment of enforcement method.
8.
For proprietary products, and commodity products with new
recommendations, proposals of PHI/PSI, other limitations and
MRLs. The basis of the proposals must be clearly given and
related to the residue and other data submitted. A statement on
the Acceptable Daily Intake (ADI) and No Observed Adverse
Effect Level (NOAEL) as derived from the toxicological data must
be submitted. Similar information from other countries or
international organizations should also be submitted as
additional information.
Additional information in the form of summaries of residue trials
may also be submitted but the complete report must be available
on request. Evaluations by the FAO/WHO Joint Meeting on
Pesticide Residues (JMPR) are acceptable as additional
information ONLY and cannot replace actual residue studies.
If residue trial information on a particular commodity is not
available, the applicant may request for information on a
representative commodity to be accepted. See Appendix I for the
grouping of commodities and the commodity which may be
regarded as representative of those in the group. The onus is on
the applicant to request for extrapolation of the data.
Residue data generated under local conditions is preferred but
data from other countries/locations with similar condition which
reflect the principal growing regions of the recommended crop
9.
10.
11.
96
12.
13.
C.
may
be
accepted. Published reports on relevant trials
by researchers are acceptable as additional information.
For major crops, which are paddy, palm oil, cocoa beans, and
black pepper, at least one field experiment must be generated
under local condition.
Residue trials on certain commodities may not be required under
certain situations such as when an insecticide/ fungicide is
applied as a seed treatment or at the nursery stage of a
perennial crop. (see Appendix III for the list of residue data
exemption)
RESIDUE TRIALS
1.
The FAO Guidelines on Producing Pesticide Residues Data from
Supervised Trials, 1990, Part 3 on Residue Trials in Crops
should be used as a basis in the design and execution of residue
field trials. Where appropriate, Good Laboratory Practices (GLP)
should be followed in carrying out the studies.
2.
For crops not included in the Codex Classification of Foods and
Animal Feeds (Guide to Codex Recommendations concerning
Pesticide Residues, Part 4), the applicant is advised to submit a
proposed residue trial protocol to the Pesticides Board for
approval before commencing the trial. Appendix II contains
examples of protocols for residue trials on oil palm and cocoa
and residue requirements.
3.
Field experiments must reflect the proposed use with respect to:
 The rate and mode of application;
 The number and timing of applications and
 The formulations proposed
4.
The location of the field experiments should reflect the principal
growing regions of the crop.
The field experiments must provide for residue dissipation or
decline studies in which samples are taken at intervals during the
period from the last applications of the pesticide to normal
harvest. Sample for residue analysis must be taken at different
period after the last application of the pesticide. The first
97
sampling shall be done 2 hour after application (0 day).
Sample shall be taken at least 4 times at various intervals
depending on characteristic of pesticide and crop. The data
obtained should indicate the pattern of uptake of the pesticide
and its decline.
D.
5.
For pre-mixture product, a residue trial data based on a single
active ingredient of the pre-mixture product is not accepted.
6.
At least three field experiments done at different sites must be
submitted. Replicate treatment of individual sites is usually not
necessary since within-site variations are usually small compared
to the variation between sites.
7.
For fumigation trials on store products, the studies should
adequately represent those commodities which might be treated,
such as oily foods (nuts, copra), and high surface area foods
(flour). The studies should reflect the effect of parameters such
as temperature, time of exposure, dosage, pressure, aeration
time etc. on the residue reduction.
8.
For studies on livestock, data must show the level of residues
that will result in the meat (muscle, liver, kidney and fat), poultry,
(muscle, liver, kidney and fat), eggs and milk. The FAO
Guidelines on Producing Pesticide Residues Data from
Supervised Trials, 1990, Part 4 on Metabolism Studies and
Supervised Residue Trials in Animals may be used in carrying
out the studies.
9.
Additional information on the reduction or concentration of
residues due to post-harvest processing or household cooking
would also be useful.
10.
All data belonging to another company can only be evaluated if a
letter of authorization is given.
RESIDUE TRIAL REPORT
1.
The behavior of the pesticide deposit from application until
harvest, possible formation of metabolites and identity of the
metabolites should be reported in order to predict residue levels
at harvest and to reach a preliminary judgement on the
acceptability of the residues. The report should be certified by an
98
authorized person of the
agency
or
research
institution carrying out the field trial and must contained the
following information.
(a) General information
 Pesticide (active ingredient and trade name);
 Formulation;
 Trial number and type (field, glasshouse);
 Commodity (crop, animal etc);
 Variety;
 Test locations (country and site);
 Soil characteristics, pH, physical and chemical
properties;
 Name(s) and signature(s) of the person(s)
responsible for the trial.
(b)
Application data for field trials.
 Crop planting or sowing date; & harvest date
 Plot plan, crop layout or cropping system;
 Plot size or number of plants per plot/unit area;
 Number of plots per treatment;
 Method of application and equipment;
 Number of applications and application dates;
 Application details (overall, banded or circle);
 Dose rate – weight of a.i. per hectare
(in kg or g a.i/ha)
- weight/volume of formulation/hectare
- applied dilution
 Climatic conditions during and after applications
preferably for the whole period of the trial;
 Other pesticides applied to the trial plot; and
 Growth stage at (last) treatment.
(c)
Sampling data
 Growth stage at sampling;
 Method of sampling;
 Sampled part(s);
 Number of units in sample, if relevant;
 Sample weight and preparation (trimming, washing
or other common practices in preparing the
commodity);
99




Control and
treated
samples;
Date of sampling with time interval between last
application and sampling;
Storage conditions before transporting to laboratory
and
Date shipped.
E.
RESIDUE ANALYSIS REPORT
Analysis of major metabolites should also be included. Data obtained
from surface striping are not acceptable except for crops where other data
on that crop have established that the total residues are in fact only
surface residues.
(a) Details on the method used.
 Full description or adequate reference;
 Apparatus;
 Chemicals and reagents;
 Data on selectivity of method;
 Data on limits of determination and quantification of
the method for the commodity in question;
 Adequate recovery data at levels corresponding to
those found in practice. The raw agricultural
commodity, or a macerate thereof, should be
fortified for the recovery tests, and not the crop
extracts. For data to be accepted, the % recovery
must be within the range of 70%-120%. The
recovery tests should be at levels corresponding to
those found in practice and actual analysis of
treated samples. Evidence on the workability,
reproducibility, selectivity and sensitivity of the
method must be submitted.
 A statement on whether or not the results have
been corrected for blanks, recoveries or both.
 In all cases, Good Laboratory Practices (GLP) or
International Standard Scheme Accreditation must
be adhered to.
(b)
Preparation of sample.
Peeling, chopping, washing, removing of soil, drying,
separation of oil or fat or juice, cooking, separation of
seed from the pulp, milling.
100
(c)
Presentation
of data.
All analytical data obtained from the analysis of samples
should be provided, and not just a summary or an
average figure. It should be clearly stated how the
residues
are
calculated
and
expressed.
Chromatographic and/or spectrophotometric evidence to
support the analysis data must be submitted. Raw data
from the laboratory need not be submitted but must be
available on request.
REFERENCES
1.
Codex Alimentarius Commission Vol. 2 – Pesticides Residues in
Food, 1993.
2.
EPA Code of Federal Regulations, 40, Parts 150-189, 1986
3.
EPA Good Laboratory Practices Standards, Code of Federal
Regulations, 40, Part 160, 1990
4.
FAO/WHO Codex Alimentarius Commission Guidelines
Producing Residues Data for Supervised Trials, 1990 in 5 Parts
5.
FAO Manual on the Submission and Evaluation of Pesticide
Residues Data for the Estimation of Maximum residue Levels in
Food and Feed, 2009
6.
Official Journal of the European Communities, Vol. 4.89, 1989
7.
Principles for Identifying Unacceptable Pesticides, The Swedish
National Chemicals Inspectorate 1992
8.
Report on Short-term Consultancy by J.A.R. Bates to the
Malaysian-German Pesticide Project 1987
9.
United States Environment Protection Agency Pesticide
Assessment Guidelines, Sub-division O, Residue Chemistry
on
101
IMPORTANT NOTES
1.
THE COMMODITY GROUPS OF APPENDIX I MAY
CONTAIN THE NAMES OF ONLY THE MORE
IMPORTANT OR FAMILIAR COMMODITIES. IF A
COMMODITY IS NOT LISTED IN THE GROUP IT IS
SUPPOSED TO BE, REFER TO THE PESTICIDES
BOARD OR CODEX “INDEX OF FOOD AND ANIMAL
FEED COMMODITIES” TO DETERMINE THE
COMMODITY GROUP OF THAT COMMODITY.
2.
IN SOME GROUPS, ANY COMMODITY IN A GROUP
CAN REPRESENT ANOTHER COMMODITY IN THE
SAME
GROUP
IN
RESIDUE
TRIALS.
NOTWITHSTANDING THAT HOWEVER, IF THE
PESTICIDES BOARD IS OF THE OPINION THAT THE
RESIDUE TRIALS OF A COMMODITY DO NOT TRULY
REPRESENT THE EXPOSURE TO PESTICIDES OF
ANOTHER
COMMODITY
FOR
WHICH
THE
PESTICIDE IS RECOMMENDED, THEN RESIDUE
TRIALS OF THE SPECIFIC COMMODITY FOR WHICH
THE PESTICIDE IS RECOMMENDED WILL BE
REQUIRED.

GUIDELINES ON REGISTRATION OF PESTICIDES

Transcription

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