Comparison of Product Chemistry Requirements and Key Points Analysis for Pesticide Registration in China, the US and Europe

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Product chemical data is the most basic part among the pesticide registration dossier. In addition to identity information, it also includes the 5 batch analysis of the technical materials, phys-chem properties and physical hazards for both technical materials and preparations, and technical properties for preparations. Generally, tests are needed to generate data for the four parts.

Since China's pesticide registration reviewed in accordance with the new requirements, a relatively large part of the products have been rejected due to the uneven quality of product chemical data. In addition, with the growth of domestic pesticide companies in recent years, the demand for pesticide registration in Europe and the United States has gradually emerged. This article will compare the product chemistry requirements for pesticide registration in China, the US and Europe, hoping to help companies in pesticide registration in various countries.

 

1. 5 Batch Analysis

The 5 batch analysis of technical materials include both qualitative and quantitative analysis. With this report, the specifications of the technical materials can be determined, relevant impurities that are harmful to human health or the environment can be found (if exist). It can also be used to assess whether the new source is equivalent to the registered source (i.e. technical equivalence assessment). The requirements for 5 batch analysis in China, the US and Europe are basically similar but slightly different, details can be found in Table 1.

 

Table 1 Comparisons of 5 batch analysis requirements in China, the US and Europe

 

China

EU

US

Endpoint

Batch analysis

Analytical profile of batches

Preliminary analysis

Guidelines

NY/T 2886-2016

Test guidelines on batch analysis of technical material for pesticide registration

SANCO/3030/99

OPPTS 830.1700

Sample requirements

Representative batches

Within the last five years of manufacturerepresentative batches (non-continuous) from industrial scale production

Representative batches

Qualitative analysis

Content of active substance, relevant impurities, significant impurities in quantities of 1 g/kg or more

All substances account for at least 980 g/kg of the material analyzed

Quantitative analysis

UV/IR/NMR/MS for active substance

Either one of UV/IR/NMR/MS for impurities

Depends on the specificity of the analytical method

Refer to EU requirements

Others

Highly toxic substances

insolubles substance

Highly toxic substances

Solvents

Raw materials

None

 

Representative batches of the technical materials are needed for all three countries. Among them, the EU has the most specific sample requirements. Generally, samples are required to be non-continuous batches produced within the last 5 years, and it is best to span different seasons to fully reflect the changes in the external environment and raw materials for production. In the early years, some companies selected samples with low impurity content and high active ingredient content to carry out 5 batches analysis. This will eventually lead to product specification that is too high and difficult to achieve in actual production, and the analysis may have to be repeated with representative batches.

For qualitative analysis, China requires the report includes four spectra analysis for active substance, and at least one of the four spectra analysis for impurities. The EU depends on the specificity of the analytical method. If the analytical method is not a highly specific method, confirmation of analyte identification is required using another highly specific method.

In addition, both China and Europe require analysis on some highly toxic substances that may exist based on production processes of the technical material. 5 batches analysis report for China pesticide registration generally also contain the analysis of insolubles substance, while the EU pays special attention to the residues of highly toxic solvents and raw materials.

 

2. Phys-chem Properties

Physical and chemical properties data can be used as the basis for substance identification, such as appearance, boiling point, vapor pressure, etc. In the event of an accident or leakage, the relevant departments can use these data to identify the substance. In addition, these data can also be used to monitor the production process to observe whether there are major changes in the production process. Data like pH and stability can be used for hazard assessment during storage and transportation. Finally, the physical and chemical properties data can also assist the risk assessment and exempt other registration-related tests. For example, ultraviolet-visible light absorption data can be used to infer the possibility of photolysis; octanol-water partition coefficient can be used to evaluate the bioaccumulation of a substance. If the log Kow value is small, it can be considered that the bioaccumulation of the substance is low. In this case, accumulation test is not needed. Comparisons of physical and chemical properties endpoints for pesticide registration in China, the US and Europe are shown in Table 2 and 3.

 

Table 2 Comparisons of physical and chemical properties endpoints for technical material registration in China, the US and Europe

 

China

EU

US

Appearance

Yes

Yes

Yes

Boiling/Melting point

Yes

Yes

Yes

Vapor pressure

Yes

Yes

Yes

Dissociation constant

Yes

Yes

Yes

Partition Coefficient

Yes

Yes

Yes

Spectra

UV

UV/IR/NMR/MS

UV

Solubility

Water, organic solvent

Water, organic solvent

Water

Hydrolysis/Photolysis

Yes

Environmental fate data

Environmental fate data

Surface tension

 

Yes

 

pH

Yes

 

Yes

Density

Yes

 

Yes

Stability

Heat, metal and metal ions

 

metal and metal ions, elevated and ambient temperature

Corrosion characteristics

Package material

 

Package material

Viscosity

  

Yes

 

Table 3 Comparisons of physical and chemical properties endpoints for end-use product registration in China, the US and Europe

 

China

EU

US

Appearance

Yes

Yes

Yes

pH, acidity, alkalinity

 

Yes

Only pH

Density

Yes

Yes

Yes

Surface tension

 

Yes

 

Viscosity

Yes

Yes

Yes

Miscibility

Yes

 

Yes

Stability

Ambient temperature

Elevated and ambient temperature

Ambient temperature

 

Among the above endpoints, the difference in requirement for stability is relatively large. The comparisons of requirements between China, the US and Europe are shown in Table 4.

 

Table 4 Comparisons of requirements of ambient storage stability for pesticide registration in China, the US and Europe

Storage Stability at Ambient Temperature

 

China

EU

US

Guidelines

NY/T 1427-2016

None

OPPTS 830.6317

Temperature

Recommend at30±2

Room temperature

Recommend 20 or 25

Time

2 years

2 years

Extrapolate from 1 year or 2 years

Sampling intervals

0,3,6,12,24 month

At least 5 time points

0,3,6,12,24 month

0,3,6,9,12,(18,24)month

Test items

Appearance, weight loss, content change of active substance, relevant impurities and other substances in control, technical properties

Appearance, content change of active substance and relevant impurities, technical properties

Appearance, content change of active substance and relevant impurities

 

Besides, the comparisons of requirements of phys-chem endpoints for pesticide registration in China, the US and Europe are shown in Table 5

 

Table 5 Comparisons of requirements of phys-chem endpoints for pesticide registration in China, the US and Europe

 

China

EU

US

Melting/Boiling point

Purified active substance and TGAI

Purified active substance, provided when the melting/boiling point is below 360,or provide the temperature of decomposition or sublimation

Melting point is required when the TGAI is solid at room temperature.

Boiling point is required when the TGAI is liquid at room temperature.

Vapor pressure

-

Test at 20 or 25°C;

If the vapor pressure is less than 10-5 Pa at 20, the vapor pressure at 20°C or 25°C shall be estimated by a vapor pressure curve with measurements at higher temperatures.;

For solids or liquids, the Henry's constant needs to be calculated

Not required for salts.

Dissociation constant

-

Tested at 20;

The identity of the dissociated species formed shall be reported;

For salts, the pKa value of the the non-dissociated form of the active substance shall be given.

Required when the test substance contains an acid or base functionality (organic or inorganic) or an alcoholic functionality (organic).

Partition coefficient

 

Reported for 20°C or 25 °C. The effect of pH (4 to 10) shall be investigated when the active substance has a pKa value between 2 and 12.

Required if technical chemical is organic and non-polar.

Solubility

Organic solvent: polar, non-polar and aromatic

Water: determine in the neutral. If the pKa is between 2 and 12, water solubility shall also be determined in the acidic range (pH 4 to 5) and in the alkaline range (pH 9 to 10).

Organic solvent: if less than 250 g/L at 15 to 25 °C; in Aliphatic hydrocarbon, Aromatic hydrocarbon, Halogenated hydrocarbon, Alcohol, Ketone and Ester

Only water solubility is required

pH, acidity, alkalinity

 

For aqueous products, the pH value shall be determined.

For solid and non-aqueous liquid products which are to be applied as aqueous dilutions the pH of a 1 % dilution shall be determined.

For products which are acidic (pH < 4) or alkaline (pH > 10) the acidity or alkalinity shall be determined.

Only pH is required

Viscosity

 

For liquid formulations the viscosity shall be determined at two shear rates and at 20°C and 40°C and reported together with the test conditions.

 

 

For physical and chemical properties, in addition to testing, data waivers can also be applied. There are three common reasons for data waiver:

1. Waive based on characteristics, such as viscosity, only liquid samples need to be tested;

2. Waive based on formulation types, usage methods, storage conditions, etc. If the product does not come into contact with metals and metal ions during storage and use, this part of the stability test is not required;

3. Waive based on the feasibility of testing. If the melting point exceeds 1000℃ and there is no testing method, a waiver can be applied.

 

In addition, many physical and chemical properties data can also be obtained through literature search, such as CRC handbook, official review report, Pubchem, ePesticide Manual and other databases. When citing literature data, generally, only data that is not affected by the production or data for pure substances can be cited. Moreover, Europe and the United States will also require to provide the original data source and obtain the permission from data owner to use the data.

 

3. Physical Hazards

Physical hazards mainly include oxidizing property, flammability, explodability, which are used to predict and prevent possible combustion and explosion hazards during storage, transportation and use. Data is required for both technical materials and the end-use product. Comparisons of requirements of physical hazard endpoints for pesticide registration in China, the US and Europe are shown in Table 6.

 

Table 6 Comparison of requirements of physical hazard endpoints for pesticide registration in China, the US and Europe

 

China

EU

US

Oxidizing property

 

Conclusions can be drawn through theoretical reasoning through structure according to EU CLP requirements

Required when the product contains an oxidizing or reducing agent.

Flammability

 

Required when the product contains combustible liquids.

Explodability

 

Required when the product is potentially explosive.

 

According to the EU CLP regulations, the explosiveness of a substance is related to certain groups in the molecule that will react and increase the temperature or pressure very rapidly. It is generally considered that C-C unsaturated, C-metal, N-metal, adjacent nitrogen atoms, adjacent Oxygen atoms, N-O, N-halogen atom, O-halogen atom are explosive groups. If these groups are not contained in a molecule, the substance will be considered as having no explosive potential and testing is not required. In addition, if a organic compound does not contain oxygen, fluorine or chlorine, or contains these elements but these elements are only bonded with carbon or hydrogen, or a inorganic compound does not contain oxygen or halogen atoms, it will be regarded as a non-oxidizing substance and does not need to carry out tests for oxidizing property.

 

4. Technical Properties

The technical properties are only required for preparations. The United States has no technical properties requirements, and the requirements of China, the EU and FAO are basically the same. Under China's pesticides registration requirements, technical properties are related to product formulation types and related product specifications, and the pesticides can be tested in accordance with the corresponding product specifications for each formulation types. There is no specific product specifications in the EU. Data gap analysis needs to be carried out based on the characteristics of the pesticide to ensure that there are sufficient data to prove that the product can be used safely. However, FAO product specifications can always be used as references.

 

Reference

  1. Announcement of the Ministry of Agriculture No. 2569 "Pesticide Registration Data Requirements" Annex 1 Interpretation and Detailed List of Registration Data Requirements for Pesticide Technical Materials (Technical concentrates)
  2. Announcement of the Ministry of Agriculture No. 2569 "Pesticide Registration Data Requirements" Annex 2 Interpretation and Detailed List of Registration Data Requirements for Pesticide Preparations
  3. Announcement of the Ministry of Agriculture No. 2569 "Pesticide Registration Data Requirements" Annex 13 Product Quality Specifications and Physical and Chemical Properties of Different Formulation Types of Pesticide Preparations
  4. NY/T 1427-2016 Guidelines for storage stability testing of pesticides at ambient temperature
  5. NY/T 2886-2016 Test guidelines on batch analysis of technical material for pesticide registration
  6. REGULATION (EU) No 283/2013
  7. REGULATION (EU) No 284/2013
  8. Recommendations on the Transport of Dangerous Goods
  9. 40 CFR Part 158 Data Requirements for Pesticides
  10. EPA Product Properties Test Guidelines OPPTS 830 Series

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