In 2017, China reformed its pesticide regulatory system and 3 types of risk assessment reports are newly required for pesticide registration:
- dietary/residue risk assessment
- health risk assessment
- environmental risk assessment
These assessments are based on the same fundamental principle which compares predicted exposure level and acceptable exposure level. In practice, the process can be complicated and demanding and varies based on pesticide scope, registration condition, organism exposed, availability of data and evaluation method/model. These factors also directly determine if higher tier tests and evaluation are required to determine the overall risk.
Product Use Scope
Food/feed crop use
Field use pesticide
New pesticide, new formulation, new content, new mixture, new use scopeandnew application method as well as me-too/similar formulation for different use scope/application method
New pesticide, new formulation, new content, new mixture, new use scopeandnew application method
Residue trial, toxicological, ADME and metabolism study, food consumption data, animal feeding, stability test, residue test of processed food
Oral, dermal and Inhalation toxicity data, simulated/field exposure test
Environmental behavior andecotoxicity(laboratory, simulated, mesocosm and in-field)
Route of exposure considered
Oral, Dermal, Inhalation(only required for mosquito coils and aerosols )
Multiple routes in different environmental organisms
NEDI/ ADI×63 or NESTI/ ARfD×63
MRL can be utilized to calculate NEDI if residue data was unavailable
Unite Exposure ×Rate×Area/ Weigh of Applicator/acceptable operator exposure level(AOEL)
Predicted environmental concentration/predicted no effect concentration
Official Assessing Model Available
CoPrisk(only for non-paddy crop using hand sprayer)
CML Model(coil, vaporizing mat and liquid vaporizer )
If RQ was greater than 1, risk mitigation measure will be considered (MRL renewal, dosage adjustmentandregistration vetoed, crop use cancellation, crop use injection, GAP modification etc.)
Ifpreliminaryassessment indicates unacceptable risk, high tier test/assessment will be required, either by refining hazard or exposure parameters.
From the table above we can see that pesticide dietary/residue risk assessment is a comparatively straightforward procedure but is intrinsically linked to new requirements listed in “GB 2763 National food safety standard Maximum residue limits for pesticides in food”, which is the current national MRL regulation universally adopted for quality supervision of both domestic and imported agricultural commodities.
2.ESSENTIAL TECHNICAL GUIDELINES
Before 2010, the former Ministry of Health (now referred to as the NHC) was mainly responsible for developing pesticide MRLs in the form of food hygienic safety standard. In tandem with this MoA (now referred to as the MoARA) also developed a series of MRLs as the quality standard for agricultural commodities. Overlap and inconsistency was a major flaw of this regulatory system. In 2009, China enacted a new Food Sanitation Act, which designated MoA to develop pesticide MRLs and relevant testing methods and agricultural practice. The National Committee on Pesticide MRL Standard was formed by the MoA in 2010 and a series of technical guidelines regarding MRL establishment were published after that. The most notable progress made during this period was the development of the national MRL standard, GB 2763 which unified the previously disparate MRL development systems.
MoA Announcement 1490
Crop Grouping for the Establishment of Pesticide MRLs
20 Nov 2010
MoA Announcement 1825
Guideline for the Establishment of Daily Acceptable Intake(ADI) of Pesticide
25 Aug 2012
MoA Announcement 2308
Guideline for the Risk Assessment of Pesticide Residue in Food and Guideline for the Establishment of Pesticide MRLs in Food
8 Oct 2015
MoA Announcement 2386
Guideline for the Establishment of National Standard for Testing of Pesticide Residue
11 Apr 2016
MoA Announcement 2586
Guideline for the establishment of Acute Reference Dose(ARfD) of Pesticide
30 Sep 2017
3.FUNDAMENTALS AND PROCEDURES OF DIETARY RISK ASSESSMENT
All types of pesticide risk assessment consist of 4 sections: hazard identification, hazard characterization (dose-effect relationship evaluation), exposure assessment and risk characterization. When it comes to dietary/residue risk assessment, 4 parts are involved: toxicological assessment, residue chemistry assessment, dietary intake assessment and conclusion.
4.VARIABLES AND CONDITIONS
In late 2017, China ICAMA released a template of Report on pesticide dietary/residue risk assessment to facilitate dossier preparation under the new data requirements.
The main body of the Report is compiled into 4 parts, corresponding to the procedures of the assessment. Each part outline the key results obtained in regulatory studies and other guidelines/data referable.
1. Toxicological Assessment
In this part, the applicant needs to present the proposed ADI and ARfD in the Report, which should be developed based on MoA Announcement 1825 and the MoA Announcement 2586. Furthermore, a recommended agricultural standard, “NYT 2874-2015 Pesticide Acceptable Daily Intake” was also published in 2015. The standard listed ADIs for 554 pesticides, which greatly facilitate the applicant and researchers involved. One thing to be aware of is ADIs and ARfDs are continuously updated based on the latest scientific data and affect the outcomes of the assessment, as well as the MRLs and migration measures adopted. The validity and conditions for exemption/grouping/extrapolation and categorization are summarized as follows:
Conditions for Temporary ADI:
Grouping/Extrapolation(single ADI adopted on multiple pesticides):
Exempted from ADI establishment(exempted from MRL):
It is well substantiated that there is no risk of long-term exposure
Special conditions for ARfD:
ADI and ARfD:
If an ARfD was lower than existing ADI, an amendment to ADI will be considered;
Periodic Review on MRL/EMRL
An EstablishedMRL will be valid for 15 years generally, but the validity will be only 5 years for temporary MRL or EMRL(Extraneous Maximum Residue Limit)
Conditions for temporary MRL:
MRL was based on temporary ADI;
2. Residue Chemistry
In the new data requirements, the minimum numbers of trial sites have doubled for staple crops, vegetables and fruits and regional distribution of these sites was recently determined by ICAMA. In compiling the Report, The applicant should summarize the GAP conditions, STMR, HR, method and numbers of sampling, transportation and storage condition and trial time, number of application, pre-harvest interval, and residue value in each trial site should also be listed. Furthermore, stability study of residue in stored food, tests of residue in processed agricultural commodities and animal feeding were additionally and particularly required for certain pesticide registration conditions:
Condition of Registration
Stability test of residue in stored food
Formulationcontaining new active ingredient will be unconditionally required;
For new formulation type,newcontent/combination of active ingredients and new crop use using exiting as well as me-too and similar formulation for new crop use,referenced data with proper attribution will be acceptable;
Guideline for the stability testing of pesticide residues in stored commodities of plant origin
Residue in processed food
Formulationcontaining new active ingredient;
New formulation type,newcontent/combination of active ingredients and new crop use using exiting as well as me-too and similar formulation for new crop use;
Only required for crop use that may have concentrated residue in proceed food
Guideline for the Testing of Pesticide Residue in Processed Agricultural Commodities
Only required forformulationcontainingnewactive ingredient used on feed crop
2 drafted guidelines
Stability of pesticide residue may vary with crop varieties and nutrient contents. NYT 3094-2017 specified the scopes, representative crops and minimal numbers of tested crops for 5 groups of commodities: high water content, high oil content, high protein content, high starch content and high acid content. If residue of the pesticide was stable(less than 30% degradation within trial period) in 5 groups of commodities, subsequent registration for new crops will be exempted from stability testing. If not, subsequent applicant should perform the stability test on the proposed crop and subsequent analysis of residue trials should be completed within the stability period identified. The crop tested and stability period identified should also be presented in the report. Oil crops, fruits and vegetables are generally considered as having a higher concentration in processed food than in raw agricultural commodities and the concentration also varies with processing method, categories of raw agricultural commodity and processed food. The objective of the study is to obtain a PF value (Processing Factor), the ratio of the residues in raw agricultural commodities and processed agricultural commodities, which will be used for STMR correction and should be presented in the Report. A PF obtained from one crop/method/ food route can be extrapolated on other commodities subject to same or similar processing method. NYT 3095 listed all the commodity, processing method and crop affected, as well as the PF extrapolation details. On 22 Oct 2018, ICAMA disclosed 2draft on animal feeding tests for consultation and applicant may fill in administering method, interval after residue data accordingly after final release early next year:
- Guideline for the testing of pesticide metabolism in livestock;
- Guideline for the testing of pesticide residues in livestock;
3. Exposure Assessment
The exposure model is based on dietary intake data in the “China's National Nutrition and Health Survey 2002”, which was disclosed as early as 12th Oct 2004. Chinese national daily food intake is 1.0286kg, consisting of intakes of 19 sub food categories(risk assessment group) ranging from 0.009kg to 0.2333kg and each food category represents multiple crops/agricultural commodities. When assessing certain pesticide, edible crops previously registered will be identified to determine food categories that contributing residue exposure. Then, arithmetic products of each intake of this food category and residue level (STMR, corrected STMR or MRL) are summed together to obtain the total residue intake.
Finally, the applicant needs to conclude a comparison between total residue intake and national acceptable daily intake (ADI×63).
Apparently, the assessment uses simple mathematics consisting of just basic multiplication and summation, there are multiple consideration and limitation for applicants and researchers in practice:
- If a pesticide was registered on multiple edible crops in different food categories (risk assessment group), but usually only one STMR can be accessible to the applicant (obtained during the registration trial on the proposed crop), as a consequence, national MRLs will be utilized for the calculation and the actual risk is often overestimated;
- Currently in GB 2763-2016, only 4140 National MRLs for 433 pesticides in 286 crop/commodities have been included, which narrows the implementation of practical assessment. If crops/commodities involved do not have a national MRL then an international MRL adopted in other regulatory systems can also be utilized.
5.PROSPECT ON MRL REGULATION
China has transformed its MRL regulatory system and now operates using risk assessment. The teething problems associated with this huge change are still being worked out. There are still issues revolving around lack of supporting data on toxicity, food processing, animal feed, analytical methods and scientific guidance.
To achieve the plan of 10,000 national MRLs by the end of 2020, 5000 more MRLs will be developed in the following manner:
- 2750 MRLs will be newly developed, of which 750 are for pesticide/crop registered but not yet established with MRL, 1500 are for fruits and vegetables and other fresh commodities and 500 are for Chinese characteristic commodities;
- About 2700 MRLs will be transformed from CAC (Codex Alimentarius Commission) standard consisting of 1673 MRLs for plant-origin commodities, 753 MRLs for animal-origin commodities and 276 MRLs for feed. The transformation will combine the risk assessment based on the dietary pattern in China and the monitoring results of residues in circulated commodities. CAC MRL, ADI developed by FAO/WHO and Chinese national dietary data will be assessed and only MRLs that received positive result can be transformed into national MRL. The most registered pesticides and top planted/consumed crop will also be selected and market monitoring data of residue will be collected and compared with the corresponding CAC standard. If 95% of the commodity was qualified, the CAC standard can also be transformed into national MRL.
- China also plans to develop 200 MRLs for imported commodities and 500 uniform MRLs for pesticides/crops not yet established with MRLs. Technical guidance on how to develop MRLs for imported commodities is still being formulated.