Amendment to the Ordinance for Enforcement of the Food Sanitation Act and the 
Specifications and Standards for Foods, Food Additives, Etc. 
 
The government of Japan will designate Difenoconazole as an authorized food 
additive and establish the standards for use and the compositional specifications. 
 
Summary 
Japan prohibits the sale etc. of food additives that are not designated by the Minister 
of Health, Labour and Welfare (hereinafter referred to as “the Minister”) under 
Article 10 of the Food Sanitation Act (Act No. 233 of 1947; hereinafter referred to as 
“the Act”). In addition, when specifications or standards for food additives are 
stipulated in the Specifications and Standards for Foods, Food Additives, Etc. 
(Ministry of Health and Welfare Notification No. 370, 1959) pursuant to Article 11 of 
the Act, Japan prohibits the sale etc. of those additives unless they meet the 
specifications or the standards. 
 
In response to a request from the Minister, the Committee on Food Additives of the 
Food Sanitation Council under the Pharmaceutical Affairs and Food Sanitation 
Council (hereinafter referred to as “the Committee”) has discussed the adequacy of 
the designation of Difenoconazole as a food additive. The conclusion of the 
Committee is outlined below. 
 
Outline of conclusion 
The Minister, pursuant to Article 10 of the Act, should designate Difenoconazole as 
a food additive unlikely to harm human health and establish the standards for use 
and the compositional specifications pursuant to Article 11 of the Act (see 
Attachment for the details). 
   
 
Difenoconazole 
ジフェノコナゾール 
 
Standards for Use (draft) 
 
Difenoconazole is permitted for use in potatoes. It shall not remain at levels exceeding 
0.004 g/kg of potatoes. 
 
Compositional Specifications (draft) 
 
Substance Name  Difenoconazole 
Structural Formula 
 
 
 
Molecular Formula  C19H17Cl2N3O3 
Molecular Weight  406.26 
Chemical Name [CAS number] 
3-Chloro-4-[(2RS,4RS;2RS,4SR)-4-methyl-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-
2-yl]phenyl 4-chlorophenyl ether  [119446-68-3] 
Content  Difenoconazole contains not less than 94.0% of difenoconazole (C19H17Cl2N3O3). 
Description  Difenoconazole occurs as a white to yellow-brown powder. 
Identification 
Determine the absorption spectrum of Difenoconazole as directed in the Disk Method 
under Infrared Spectrophotometry, and compare with the Reference Spectrum. Both 
spectra exhibit similar intensities of absorption at the same wavenumbers. 
Melting Point  76–83C. 
Purity O O
CH3O Cl
ClN
NN 
 
Lead  Not more than 2 μg/g as Pb (2.0 g, Method 1, Control Solution: Lead Standard 
Solution 4.0 mL, Flame Method). 
Assay 
Test Solution and Standard Solution  Weigh accurately about 50 mg each of 
Difenoconazole and difenoconazole for assay. Add exactly 20 mL of the internal standard 
solution to each, dissolve by adding acetone to make exactly 100 mL. 
Internal Standard Solution  Dissolve 75 mg of fludioxonil for assay by adding 
acetone to make exactly 50 mL. 
Procedure  Analyze 2-μL portions of the test solution and the standard solution by 
gas chromatography using the operating conditions given below. Determine the peak 
area ratios (QT and QS) of difenoconazole to fludioxonil for the test solution and the 
standard solution, respectively. Determine the content of difenoconazole by the formula: 
 
Content (%) of difenoconazole C19H17Cl2O3N3O3 
= Weight (mg) of difenoconazole for assay
Weight (mg) of the sample × Q
Q ×100 
  
Operating conditions 
Detector: Flame ionization detector. 
Column: A fused silica tube (0.25 mm internal diameter and 30 m length) 
coated with a 0.25 μm thick layer of dimethylpolysiloxane for gas 
chromatography. 
Column temperature: Maintain the temperature at 100C for 1 minutes, raise 
at 30C/minute to 250C, then raise at 6C/minute to 300C, and maintain 
the temperature at 300C for 2 minutes. 
Injection port temperature: A constant temperature of around 250°C. 
Detector temperature: A constant temperature of around 300C. 
Carrier gas: Helium. 
Flow rate: Adjust the retention time of difenoconazole to about 10–15 
minutes. 
Injection method: Split. 
Split ratio: 1 : 20 
 
Reagents, Solutions, and Other Reference Materials 
Difenoconazole for Assay  C19H17Cl2N3O3  [119446-68-3]  A white crystalline powder 
or powder.  
 
Content  Not less than 97.0% of difenoconazole (C19H17Cl2N3O3). 
Identification  Determine the absorption spectrum of difenoconazole for assay as 
directed in the Disk Method under Infrared Spectrophotometry. It exhibits absorptions 
at wavenumbers of about 1605 cm-1, 1585 cm-1, 1507 cm-1, 1478 cm-1, 1227 cm-1, 1048 
cm-1, 848 cm-1, and 679 cm-1. 
Assay  Weigh accurately about 10 mg of difenoconazole for assay and about 1 mg of 
1,4-BTMSB-d4, and add 1 mL of deuterated acetone to dissolve them together. Transfer 
the resulting solution to an NMR tube of 5 mm in external diameter, and stopper 
tightly. Measure 1HNMR spectra using a spectrometer corresponding to a proton 
resonance frequency of 400 MHz or more under the following operating conditions. 
Assuming the signal of 1,4-BTMSB-d4 as  0 ppm, when the signal area intensities at 
around  7.33–7.35 ppm and  7.48–7.53 ppm are designated as A1 (corresponding to 1 
hydrogen atom) and A2 (corresponding to 1 hydrogen atom), respectively, confirm that 
A1/A2 is 1.0. Then, assuming the signal area intensity of 1,4-BTMSB-d4 as 18.00, when 
the sum of A1 and A2, the sum of the number of hydrogens, and the purity of 1,4-
BTMSB-d4 are designated as I, N, and P(%), respectively, determine the content of 
difenoconazole by the following formula. If the signal from difenoconazole is overlapped 
with the signal from a contaminant, do not use its signal area intensity and the 
number of hydrogens for the assay. 
 
Content (%) of difenoconazole (C19H17Cl2N3O3)  
= Weight (mg) of 1,4-BTMSB-d4 × I × P
Weight (mg) of the sample × N × 1.794 
 
Operating conditions 
Digital resolution: not more than 0.25. 
Spinning: Off. 
13C decoupling: Present. 
Acquisition time: Not less than 4 seconds.  
Spectral range: At least 20 ppm including between -5 ppm and 15 ppm. 
Flip angle: 90º. 
Delay time: Not less than 64 seconds. 
Dummy scans: Not less than 2. 
Number of accumulation: Not less than 32. 
Measurement temperature: A constant temperature at 20C–30C. 
 
Infrared Reference Spectrum  
 
Difenoconazole