GHS Classification Results by the Japanese Government

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GENERAL INFORMATION
Item Information
CAS RN 35367-38-5
Chemical Name 1-(4-chlorophenyl)-3-(2,6-difluorobenzoyl)urea; Diflubenzuron
Substance ID R02-A-035-METI, MOE
Classification year (FY) FY2020
Ministry who conducted the classification Ministry of Economy, Trade and Industry (METI)/Ministry of the Environment (MOE)
New/Revised New
Classification result in other fiscal year  
Download of Excel format Excel file

REFERENCE INFORMATION
Item Information
Guidance used for the classification (External link) GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
UN GHS document (External link) UN GHS document
Definitions/Abbreviations (Excel file) Definitions/Abbreviations
Model Label by MHLW (External link)  
Model SDS by MHLW (External link)  
OECD/eChemPortal (External link) eChemPortal

PHYSICAL HAZARDS
Hazard class Classification Pictogram
Signal word
Hazard statement
(code)
Precautionary statement
(code)
Rationale for the classification
1 Explosives Not classified (Not applicable)
-
-
- - There are no chemical groups associated with explosive properties present in the molecule.
2 Flammable gases Not classified (Not applicable)
-
-
- - Solid (GHS definition)
3 Aerosols Not classified (Not applicable)
-
-
- - Not aerosol products.
4 Oxidizing gases Not classified (Not applicable)
-
-
- - Solid (GHS definition)
5 Gases under pressure Not classified (Not applicable)
-
-
- - Solid (GHS definition)
6 Flammable liquids Not classified (Not applicable)
-
-
- - Solid (GHS definition)
7 Flammable solids Classification not possible
-
-
- - No data available. Besides, there is information that it is combustible (Accessed Sep. (2020)).
8 Self-reactive substances and mixtures Not classified (Not applicable)
-
-
- - There are no chemical groups present in the molecule associated with explosive or self-reactive properties.
9 Pyrophoric liquids Not classified (Not applicable)
-
-
- - Solid (GHS definition)
10 Pyrophoric solids Classification not possible
-
-
- - No data available.
11 Self-heating substances and mixtures Classification not possible
-
-
- - No data available.
12 Substances and mixtures which, in contact with water, emit flammable gases Not classified (Not applicable)
-
-
- - The chemical structure of the substance does not contain metals or metalloids (B, Si, P, Ge, As, Se, Sn, Sb, Te, Bi, Po, At).
13 Oxidizing liquids Not classified (Not applicable)
-
-
- - Solid (GHS definition)
14 Oxidizing solids Not classified (Not applicable)
-
-
- - The substance is an organic compound containing fluorine, chlorine, and oxygen, which are chemically bonded only to carbon or hydrogen.
15 Organic peroxides Not classified (Not applicable)
-
-
- - Organic compounds containing no bivalent -O-O- structure in the molecule.
16 Corrosive to metals Classification not possible
-
-
- - Classification is not possible because test methods applicable to solid substances are not available.
17 Desensitized explosives Not classified (Not applicable)
-
-
- - There are no chemical groups associated with explosive properties present in the molecule.

HEALTH HAZARDS
Hazard class Classification Pictogram
Signal word
Hazard statement
(code)
Precautionary statement
(code)
Rationale for the classification
1 Acute toxicity (Oral) Not classified
-
-
- - [Rationale for the Classification]
It was classified as "Not classified" from (1) - (4).

[Evidence Data]
(1) LD50 for rats: > 8,100 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015))
(2) LD50 for rats: > 5,000 mg/kg (EPA Pesticides RED (1997))
(3) LD50 for rats: > 4,600 mg/kg (JECFA (2016), JMPR (2001))
(4) LD50 for rats: > 4,640 mg/kg (EFSA (2009), EHC (1996))
1 Acute toxicity (Dermal) Not classified
-
-
- - [Rationale for the Classification]
It was classified as "Not classified" from (1) - (4).

[Evidence Data]
(1) LD50 for rats: > 5,400 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015))
(2) LD50 for rats: > 5,000 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015))
(3) LD50 for rats: > 2,000 mg/kg (EPA Pesticides RED (1997), EFSA (2009))
(4) LD50 for rats: > 10,000 mg/kg (JECFA (2016), JMPR (2001))
1 Acute toxicity (Inhalation: Gases) Not classified
-
-
- - [Rationale for the Classification]
Solid (GHS definition). It was classified as "Not classified."
1 Acute toxicity (Inhalation: Vapours) Classification not possible
-
-
- - [Rationale for the Classification]
Classification not possible due to lack of data.
1 Acute toxicity (Inhalation: Dusts and mists) Classification not possible
-
-
- - [Rationale for the Classification]
It was impossible to specify the category from (1) - (3), and the classification is not possible.

[Evidence Data]
(1) LC50 for rats: > 2.49 mg/L (EPA Pesticides RED (1997), EHC (1996))
(2) LC50 for rats (4 hours): > 2.5 mg/L (EFSA (2009))
(3) LC50 for rats (dust, 6 hours): > 2.88 mg/L (converted 4-hour equivalent value: 4.32 mg/L) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2020))
2 Skin corrosion/irritation Not classified
-
-
- - [Rationale for the Classification]
It was classified as "Not classified." from (1).

[Evidence Data]
(1) It is reported that in a skin irritation test with rabbits, after undiluted this substance was applied to the abraded skin and intact skin, no skin irritation was found after 24, 72 hours (EHC (1996), JMPR (2001), JECFA (2016), HSDB (Accessed Sep. 2020)).
3 Serious eye damage/eye irritation Category 2B
-
Warning
H320 P305+P351+P338
P337+P313
P264
[Rationale for the Classification]
It was classified in Category 2B from (1) in accordance with the GHS classification guidance for the Japanese government.

[Evidence Data]
(1) Mild eye irritation was observed in an eye irritation test with rabbits (EPA Pesticides RED (1997)).

[Reference Data, etc.]
(2) It was slightly irritating to the eye in an eye irritation test with rabbits (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015), JECFA (2016), JMPR (2001), EHC (1996), HSDB (Accessed Sep. 2020)).
4 Respiratory sensitization Classification not possible
-
-
- - [Rationale for the Classification]
Classification not possible due to lack of data.
4 Skin sensitization Not classified
-
-
- - [Rationale for the Classification]
It was classified as "Not classified" from (1).

[Evidence Data]
(1) It is reported that in a maximization test with guinea pigs (n = 10) (GLP, intradermal administration: 10% solution), slight reactions were observed after challenge in 2 animals (JECFA (2016), JMPR (2001), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2020)).
5 Germ cell mutagenicity Not classified
-
-
- - [Rationale for the Classification]
Based on (1) to (9), it was classified as "Not classified."

[Evidence Data]
(1) In a dominant lethal test with mice (exposed once by intraperitoneal injection), negative results were reported (Food Safety Commission of Japan, 2015), JECFA FAS 72 (2016)).
(2) In a micronucleus test with mouse bone marrow cells (dosed twice by gavage), negative results were obtained (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015), JECFA FAS 72 (2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2020)).
(3) In a micronucleus test using the peripheral blood of mice after single-dose oral administration, positive results were reported (JECFA FAS 72 (2016)).
(4) In a comet assay using the peripheral blood of mice after single-dose oral administration, positive results (dose-dependent at 0.3 to 3 mg/kg) were reported (JECFA FAS 72 (2016)).
(5) In a bacterial reverse mutation test, negative results were obtained (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015), JECFA FAS 72 (2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2020)).
(6) In a UDS test using human fibroblasts, negative results were obtained (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015), JECFA FAS 72 (2016)).
(7) In a UDS test using primary cultured hepatocytes of rats, negative results were obtained (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015), JECFA FAS 72 (2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2020)).
(8) In a gene mutation test using mouse lymphoma cells, negative results were obtained (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015, JECFA FAS 72 (2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2020)).
(9) In a chromosomal aberration test using CHO cells, negative results were obtained (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015), JECFA FAS 72 (2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2020)).

[Reference Data, etc.]
(10) Concerning the positive results obtained in the in vivo micronucleus test and the comet assay in (3) and (4) using the peripheral blood of mice, the JECFA Committee concluded that this substance was not genotoxic based on the weight of evidence since the results were inconsistent with the results reported in other studies and were not replicated (JECFA FAS 72 (2016)).
6 Carcinogenicity Not classified
-
-
- - [Rationale for the Classification]
Based on (1) to (4), it was classified as "Not classified."

[Evidence Data]
(1) As for the classification results by domestic and international organizations, EPA classified this substance in Group E (Evidence of Non-Carcinogenicity for Humans) (EPA Annual Cancer Report 2018 (Accessed Sep. 2020): Classification in 1995).
(2) In a two-year combined chronic toxicity/carcinogenicity study with rats dosed by feeding, increased methemoglobin was observed both in males and females at the highest dose of 160 ppm, but no treatment-related increase in the incidence of neoplastic lesions was observed. No carcinogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015), JECFA (2016), JMPR (2001)).
(3) In a two-year carcinogenicity study with rats dosed by feeding (GLP), no treatment-related increase in the incidence of neoplastic lesions was observed at doses of up to 10,000 ppm at which hematological toxicity effects were clearly observed. No carcinogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015), JECFA (2016), JMPR (2001), EPA Pesticides RED (1997)).
(4) In a 91-week combined chronic toxicity/carcinogenicity study with mice dosed by feeding (GLP), no treatment-related increase in the incidence of neoplastic lesions was observed at doses of up to 10,000 ppm at which hematological toxicity effects were clearly observed. No carcinogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015), JECFA (2016), JMPR (2001), EPA Pesticides RED (1997)).

[Reference Data, etc.]
(5) 4-Chloroaniline (CAS RN 106-47-8: PCA), which is a metabolite of this substance, is classified as a carcinogen (Carc. 2) (EU-CLP Classification Results (Accessed Sep. 2020), EFSA (2012)).
7 Reproductive toxicity Not classified
-
-
- - [Rationale for the Classification]
Based on (1) to (7), it was classified as "Not classified."

[Evidence Data]
(1) It was reported that in a three-generation reproduction toxicity study with rats dosed by feeding, no effects on fertility were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2020)).
(2) It was reported that in a two-generation reproduction toxicity study with rats dosed by feeding (OECD TG 416, GLP), at or above 500 ppm, hematological toxicity effects (such as anemia, increased methemoglobin, hemosiderosis in the liver and the spleen) were observed in parental animals, and at 50,000 ppm, reduced body weight gain (F1 males and females) was observed in pups, but no effects on fertility were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015), JECFA (2016), JMPR (2001), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2020), EFSA (2009), EPA Pesticides RED (1997)).
(3) It was reported that in a one-generation reproduction toxicity study with rats dosed by feeding, general toxicity effects (such as effects on the hematopoietic system and the liver) were observed in parental animals, but no effects on fertility were observed at or above1000 ppm (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2020)).
(4) It was reported that in a developmental toxicity study with rats dosed by gavage (day 6 to 15 of gestation), no teratogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2020)).
(5) It was reported that in another developmental toxicity study with rats dosed by gavage (gestation days 6 to 15), which was different from the study of (4), no teratogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015), JECFA (2016), JMPR (2001), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2020), EFSA (2009), EPA Pesticides RED (1997)).
(6) It was reported that in a developmental toxicity study with rabbits dosed by gavage (day 6 to 18 of gestation), no teratogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2020)).
(7) It was reported that in a developmental toxicity study with rabbits dosed by gavage (day 7 to 19 of gestation), no teratogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015), JECFA (2016), JMPR (2001), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2020), EFSA (2009), EPA Pesticides RED (1997)).
8 Specific target organ toxicity - Single exposure Category 3 (Respiratory tract irritation)


Warning
H335 P304+P340
P403+P233
P261
P271
P312
P405
P501
[Rationale for the Classification]
Based on (1), it was classified in Category 3 (respiratory tract irritation).

[Evidence Data]
(1) It was reported that in an acute (dust) inhalation toxicity test with rats (for 6 hours), sternutation and dyspnea were observed, and LC50 was 35 mg/L (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2020)).

[Reference Data, etc.]
(2) It was reported that in an acute oral toxicity test and an acute dermal toxicity test with rats and mice, no symptoms and no deaths were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015)).
9 Specific target organ toxicity - Repeated exposure Category 1 (blood system)


Danger
H372 P260
P264
P270
P314
P501
[Rationale for the Classification]
Based on (1) to (6), it was considered that the target organ was the blood system and effects were observed within the dose range for Category 1. Therefore, it was classified in Category 1 (blood system).

[Evidence Data]
(1) It was reported that in a 90-day oral toxicity test with rats dosed by feeding, an increase in white blood cell count (females) was observed at or above 100 ppm (8.09 mg/kg/day (males), 7.93 mg/kg/day (females), within the range for Category 1), and reductions in the specific gravity of the whole blood, hematocrit (Ht), and hemoglobin (Hb), a decrease in red blood cell count (RBC) (females), and decreases in absolute and relative spleen weight were observed at 300 ppm (23.9 mg/kg/day (males), 24.9 mg/kg/day (females), within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015)).
(2) It was reported that in a 13-week oral toxicity test with rats dosed by feeding (GLP), bone marrow effects (erythroblast hyperplasia), liver effects (chronic hepatitis), hematological effects (an increase in methemoglobin (females)), and spleen effects (hemosiderosis, increases in absolute and relative weight (males)) were observed at or above 160 ppm (8 mg/kg/day, within the range for Category 1); and hematological effects (decreases in RBC and Hb, an increase in reticulocyte count (Ret), an increase in methemoglobin (males)), liver effects (hemosiderosis, an increase in relative weight (females)), and spleen effects (congestion, increases in absolute and relative weight (females)) were observed at or above 400 ppm (20 mg/kg/day, within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015), JECFA (2016)).
(3) It was reported that in a 90-day oral toxicity test with dogs dosed by feeding, hematological effects (an increase in methemoglobin, decreases in RBC and Hb) were observed at 160 ppm (5.86 mg/kg/day (males), 6.68 mg/kg/day (females), within the range for Category 1) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015), JECFA (2016)).
(4) It was reported that in a one-year chronic toxicity study with dogs, hematological effects (increases in methemoglobin and sulfhemoglobin, decreases in RBC and Hb (females), increases in Ret, Heinz bodies, and platelet count (females)), liver effects (pigmentation of macrophages and Kupffer cells, an increase in absolute weight (males)), and spleen effects (an increase in absolute weight (males)) were observed at 10 mg/kg/day (within the range for Category 1) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015), JECFA (2016)).
(5) It was reported that in a two-year combined chronic toxicity/carcinogenicity study with rats dosed by feeding, a significant increase in methemoglobin was observed at 160 ppm (5.83 mg/kg/day (males), 7.05 mg/kg/day (females), within the range for Category 1) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015), JECFA (2016)).
(6) It was reported that in a two-year carcinogenicity test with rats dosed by feeding (GLP), an increase in methemoglobin (males and females), an increase in sulfhemoglobin (males), and an increase in pigmented macrophages in the liver (females) were observed at or above 156 ppm (7.00 mg/kg/day (males), 9.22 mg/kg/day (females), within the range for Category 1); and an increase in pigmented macrophages in the spleen, erythroid cell hyperplasia, decreases in RBC and Hb, an increase in pigmented macrophages in the liver (males), and an increase in sulfhemoglobin (females) were observed at or above 625 ppm (31.3 mg/kg/day, within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015), JECFA (2016)).

[Reference Data, etc.]
(7) It was reported that in a 14-week oral toxicity test with mice dosed by feeding, hematological effects (increases in methemoglobin, sulfhemoglobin, and Heinz bodies) were observed at or above 80 ppm (12 mg/kg/day, within the range for Category 2); and hematological effects (decreases in RBC and Ht, an increase in Ret), spleen effects (increased weight, hemosiderosis) and liver effects (hepatocellular hypertrophy, hepatocellular cytoplasmic vacuolization, local inflammation and necrosis of the liver, hemosiderosis) were observed at or above 400 ppm (60 mg/kg/day, within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015)).
(8) It was reported that in a 91-week combined chronic toxicity/carcinogenicity study with mice dosed by feeding (GLP), an increase in PLT, an increase in Heinz bodies, and an increase in siderocytes in the spleen were observed at or above 400 ppm (32.2 mg/kg/day (males), 35.4 mg/kg/day (females), within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015), JECFA (2016)).
10 Aspiration hazard Classification not possible
-
-
- - [Rationale for the Classification]
Classification not possible due to lack of data.

ENVIRONMENTAL HAZARDS
Hazard class Classification Pictogram
Signal word
Hazard statement
(code)
Precautionary statement
(code)
Rationale for the classification
11 Hazardous to the aquatic environment Short term (Acute) Category 1


Warning
H400 P273
P391
P501
It was classified in Category 1 from 96-hour LC50 = 0.00144 mg/L for crustacea (Palaemonetes pugio) (EHC 184, 1996).
11 Hazardous to the aquatic environment Long term (Chronic) Category 1


Warning
H410 P273
P391
P501
It was classified in Category 1 because it is not rapidly degradable (BIOWIN) and due to 21-day NOEC < 0.00006 mg/L for crustacea (Daphnia magna) (EPA RED, 1997).
12 Hazardous to the ozone layer Classification not possible
-
-
- - This substance is not listed in the Annexes to the Montreal Protocol.


NOTE:
  • GHS Classification Result by the Japanese Government is intended to provide a reference for preparing a GHS label or SDS for users. To include the same classification result in a label or SDS for Japan is NOT mandatory.
  • Users can cite or copy this classification result when preparing a GHS label or SDS. Please be aware, however, that the responsibility for a label or SDS prepared by citing or copying this classification result lies with users.
  • This GHS classification was conducted based on the information sources and the guidance for classification and judgement which are described in the GHS Classification Guidance for the Japanese Government etc. Using other literature, test results etc. as evidence and including different content from this classification result in a label or SDS are allowed.
  • Hazard statement and precautionary statement will show by hovering the mouse cursor over a code in the column of "Hazard statement" and "Precautionary statement," respectively. In the excel file, both the codes and statements are provided.
  • A blank or "-" in the column of "Classification" denotes that a classification for the hazard class was not conducted in the year.
  • An asterisk “*” in the column of “Classification” denotes that “Not classified (or No applicable)” and/or “Classification not possible” is applicable. Details are described in the column of “Rationale for the classification”. If no English translation is available for “Rationale for the classification,” please refer to the Japanese version of the results.

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