GHS Classification Results by the Japanese Government

Japanese



GENERAL INFORMATION
Item Information
CAS RN 60207-90-1
Chemical Name 1-{[2-(2,4-Dichlorophenyl)-4-propan-1-yl-1,3-dioxolan-2-yl]methyl}-1H-1,2,4-triazole (synonym: Propiconazole)
Substance ID R03-B-026-METI, MOE
Classification year (FY) FY2021
Ministry who conducted the classification Ministry of Economy, Trade and Industry (METI)/Ministry of the Environment (MOE)
New/Revised Revised
Classification result in other fiscal year FY2008  
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) MHLW Website (in Japanese Only)
Model SDS by MHLW (External link) MHLW Website (in Japanese Only)
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)
-
-
- - Liquid (GHS definition)
3 Aerosols Not classified (Not applicable)
-
-
- - Not aerosol products.
4 Oxidizing gases Not classified (Not applicable)
-
-
- - Liquid (GHS definition)
5 Gases under pressure Not classified (Not applicable)
-
-
- - Liquid (GHS definition)
6 Flammable liquids Not classified
-
-
- - Since information that a flash point is > 150 deg C (test method: unknown) (GESTIS (Accessed Aug. 2021)) was obtained, it is estimated that it exceeds 93 deg C also in the prescribed closed-cup method. Therefore, it was classified as "Not classified."
7 Flammable solids Not classified (Not applicable)
-
-
- - Liquid (GHS definition)
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 Classification not possible
-
-
- - No data available.
10 Pyrophoric solids Not classified (Not applicable)
-
-
- - Liquid (GHS definition)
11 Self-heating substances and mixtures Classification not possible
-
-
- - Test methods applicable to liquid substances are not 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)
-
-
- - The substance is an organic compound containing chlorine and oxygen (but not fluorine) which are chemically bonded only to carbon or hydrogen.
14 Oxidizing solids Not classified (Not applicable)
-
-
- - Liquid (GHS definition)
15 Organic peroxides Not classified (Not applicable)
-
-
- - Organic compounds containing no bivalent -O-O- structure in the molecule.
16 Corrosive to metals Not classified
-
-
- - It was classified as "Not classified" from information that it is non-corrosive to metals (HSDB in PubChem (Accessed Aug. 2021)).
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) Category 4


Warning
H302 P301+P312
P264
P270
P330
P501
[Rationale for the Classification]
Based on (1) to (6), it was classified in Category 4.

[Evidence Data]
(1) LD50 for rats (females): 550 mg/kg (OECD TG 425, GLP) (Risk Assessment Report (Pesticides and Additive) (Food Safety Commission of Japan, 2017), CLH Report (2015))
(2) LD50 for rats (males): 783 mg/kg (GLP) (Risk Assessment Report (Pesticides and Additive) (Food Safety Commission of Japan, 2017))
(3) LD50 for rats (females): 509 mg/kg (GLP) (Risk Assessment Report (Pesticides and Additive) (Food Safety Commission of Japan, 2017))
(4) LD50 for rats (males): 1,520 mg/kg (Risk Assessment Report (Pesticides and Additive) (Food Safety Commission of Japan, 2017))
(5) LD50 for rats (females): 1,520 mg/kg (Risk Assessment Report (Pesticides and Additive) (Food Safety Commission of Japan, 2017))
(6) LD50 for rats: 1,517 mg/kg (EPA Pesticides RED (2006))
1 Acute toxicity (Dermal) Not classified
-
-
- - [Rationale for the Classification]
Based on (1) to (9), it was classified as "Not classified."

[Evidence Data]
(1) LD50 for rats (males): > 5,000 mg/kg (OECD TG 402, GLP) (Risk Assessment Report (Pesticides and Additive) (Food Safety Commission of Japan, 2017), CLH Report (2015))
(2) LD50 for rats (females): > 5,000 mg/kg (OECD TG 402, GLP) (Risk Assessment Report (Pesticides and Additive) (Food Safety Commission of Japan, 2017), CLH Report (2015))
(3) LD50 for rats (males): > 2,000 mg/kg (GLP) (Risk Assessment Report (Pesticides and Additive) (Food Safety Commission of Japan, 2017))
(4) LD50 for rats (females): > 2,000 mg/kg (GLP) (Risk Assessment Report (Pesticides and Additive) (Food Safety Commission of Japan, 2017))
(5) LD50 for rats (males): > 4,000 mg/kg (Risk Assessment Report (Pesticides and Additive) (Food Safety Commission of Japan, 2017), CLH Report (2015))
(6) LD50 for rats (females): > 4,000 mg/kg (Risk Assessment Report (Pesticides and Additive) (Food Safety Commission of Japan, 2017), CLH Report (2015))
(7) LD50 for rabbits (males): > 6,000 mg/kg (Risk Assessment Report (Pesticides and Additive) (Food Safety Commission of Japan, 2017), CLH Report (2015))
(8) LD50 for rabbits (females): > 6,000 mg/kg (Risk Assessment Report (Pesticides and Additive) (Food Safety Commission of Japan, 2017), CLH Report (2015))
(9) LD50 for rabbits: > 4,000 mg/kg (EPA Pesticides RED (2006)
1 Acute toxicity (Inhalation: Gases) Not classified
-
-
- - [Rationale for the Classification]
Liquid (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) Not classified
-
-
- - [Rationale for the Classification]
Based on (1) to (3), it was classified as "Not classified."

[Evidence Data]
(1) LC50 (aerosol, 4 hours) for rats (males): > 5.84 mg/L (Risk Assessment Report (Pesticides and Additive) (Food Safety Commission of Japan, 2017), EPA Pesticides RED (2006))
(2) LC50 (aerosol, 4 hours) for rats (females): > 5.84 mg/L (Risk Assessment Report (Pesticides and Additive) (Food Safety Commission of Japan, 2017), EPA Pesticides RED (2006))
(3) LC50 (aerosol, 4 hours) for rats: > 5.8 mg/L (OECD TG 403, GLP) (CLH Report (2015))
2 Skin corrosion/irritation Not classified
-
-
- - [Rationale for the Classification]
Based on (1) to (3), it was classified as "Not classified."

[Evidence Data]
(1) In an acute dermal irritation/corrosion test (OECD TG404, GLP, semiocclusive, 4-hour application, observation for 21 days) with rabbits (n=3), slight erythema was observed in all animals 1 hour after patch removal, and persisted until after one week, but disappeared after three weeks. Also, slight edema was observed in 2 animals 1 hour after patch removal, and persisted in 1 animal until after 48 hours. It was reported that the primary irritation index (PII) was 1.22 (erythema/eschar score: 1/1/1, edema score: 0/0/0.7) (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), REACH registration dossier (Accessed Sep. 2021)).
(2) It was reported that, in a skin irritation test (occlusive, 24-hour application, observation for 7 days) with rabbits (n=6), slight erythema and edema were observed from 1 day after the application, but disappeared after 4 days (erythema/eschar score: 1/0.7/1/0.7/1.7/1.3, edema score: 0.3/0.7/1/0.3/1.3/1) (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)).
(3) This substance was not a skin irritant (EFSA (2017)).

[Reference Data, etc.]
(4) This substance was irritating to the skin of rabbits (JMPR (2004)).
(5) In a skin irritation test with rabbits of two strains, slight irritation was observed (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2017)).
(6) This substance was not a skin irritant (HSDB (Accessed Sep. 2021)).
3 Serious eye damage/eye irritation Not classified
-
-
- - [Rationale for the Classification]
Based on (1) to (5), it was classified as "Not classified." Also, based on the new findings, the classification result was changed.

[Evidence Data]
(1) It was reported that, in an acute eye irritation/corrosion test (OECD TG 405, GLP, observation for 7 days) with rabbits (n=3), conjunctival redness, chemosis, and discharge were observed in all animals 1 hour after the application, but regressed after 72 hours until only slight redness was observed in 1 animal, and regressed completely after 7 days (cornea opacity score: 0/0/0, iritis score: 0/0/0, conjunctival redness score: 1.3/1/1, chemosis score: 0/0.3/0.3) (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), REACH registration dossier (Accessed Sep. 2021)).
(2) It was reported that, in an eye irritation test (observation for 7 days) with rabbits (n=6), slight cornea opacity was observed, but disappeared within 72 hours after the application. In addition, slight conjunctival redness was observed, but disappeared within 48 hours after the application (cornea opacity score: 0/0.5/1, iritis score: 0/0/0, conjunctival redness score: 0/0/0.3, chemosis score: 0/0/0.3) (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)).
(3) In an eye irritation test with rabbits of two strains, slight irritation to the eye was observed (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2017)).
(4) This substance did not irritate the eye in rabbits (JMPR (2004)).
(5) This substance was not an eye irritant (EFSA (2017)).

[Reference Data, etc.]
(6) This substance was not an eye irritant (HSDB (Accessed Sep. 2021))
4 Respiratory sensitization Classification not possible
-
-
- - [Rationale for the Classification]
Classification not possible due to lack of data.
4 Skin sensitization Category 1B


Warning
H317 P302+P352
P333+P313
P362+P364
P261
P272
P280
P321
P501
[Rationale for the Classification]
Based on (1) to (3), it was classified in Category 1B. Also, based on the new findings, the classification result was changed.

[Evidence Data]
(1) It was reported that, in a Maximization test (OECD TG 406, GLP, intradermal injection: 5.0% solution) with guinea pigs (n=20), the positive rate after 24 and 48 hours was 30% (6/20 animals) and 50% (10/20 animals), respectively. (ECHA RAC Opinion (2016), Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), REACH registration dossier (Accessed Sep. 2021)).
(2) It was reported that, in a Maximization test with guinea pigs, this substance was a skin sensitizer (JMPR (2004)).
(3) This substance is a skin sensitiser (EFSA (2017)).
5 Germ cell mutagenicity Not classified
-
-
- - [Rationale for the Classification]
Based on (1) and (2), it was classified as "Not classified."

[Evidence Data]
(1) As for in vivo, negative results were obtained in all of a dominant lethal assay (single oral dose) with mice, a chromosomal aberration test (5-day repeated oral dose) using the spermatogonia and spermatocytes of mice, a micronucleus assay (single oral dose) using the bone marrow cells of mice and hamsters, and a sister chromatid exchange (SCE) test (single oral dose) using the bone marrow cells of hamsters (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), CLH Report (2015)).
(2) As for in vitro, negative results were obtained in all of multiple bacterial reverse mutation assays, a gene mutation assay using the mouse lymphoma cells, and a chromosomal aberration test using human peripheral blood lymphocytes (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), CLH Report (2015)).
6 Carcinogenicity Category 2


Warning
H351 P308+P313
P201
P202
P280
P405
P501
[Rationale for the Classification]
Based on (1) to (5), it was classified in Category 2. Based on the new information source, the classification result was changed.

[Evidence Data]
(1) As for the classification results by domestic and international organizations, the EPA classified this substance in Group C (Possible Human Carcinogen: corresponding to Category 2) (EPA OPP Annual Cancer Report 2020 (Accessed August 2021): Classification in 1992).
(2) In a two-year combined chronic toxicity/carcinogenicity study with rats dosed by feeding, no carcinogenicity was observed at doses up to 2,500 ppm (males/females: 96.5/131 mg/kg/day) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), CLH Report (2015), EPA OPP Human Health Risk Assessment (2013)).
(3) In a 2-year carcinogenicity study with mice dosed by feeding, significant increases in the incidences of hepatocellular adenoma (multiple) and hepatocellular carcinoma (multiple) were observed in males of a 2,500 ppm dose group. On the other hand, in females of the same group, there was no significant difference compared to the control group, and no carcinogenicity was observed in females (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), CLH Report (2015), EPA OPP Human Health Risk Assessment (2013)).
(4) In an 18-month carcinogenicity study with male mice dosed by feeding, a significant increase in hepatocellular adenoma (10/50 animals) was observed in a group at the highest dose of 850 ppm (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), CLH Report (2015), EPA OPP Human Health Risk Assessment (2013)).
(5) The incidence of hepatocellular adenoma in the study of (4) exceeded the background data (3/50 to 9/50 animals) of the laboratory that conducted the study. The incidence of hepatocellular carcinoma in the same group (2/50 animals) was within the background data (4/50 to 8/50 animals) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)).

[Reference Data, etc.]
(6) As a result of a mechanism test for the incidence of liver tumor, it was suggested that the liver tumor observed in male mice was associated with the induction of hepatic drug metabolizing enzymes and increased cell proliferation ability (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2017)).
7 Reproductive toxicity Category 1B


Danger
H360 P308+P313
P201
P202
P280
P405
P501
[Rationale for the Classification]
Based on (1) to (5), it was classified in Category 1B. Also, in (1), decreases in the number of births and the number of live pups, etc. were observed in offspring at a dose at which general toxicity was observed in parent animals, in (2), (3), and (5), the incidence of cleft palate was observed in rats and rabbits, and furthermore, in (4), an increase in embryonic/fetal death, and abortion or early delivery were observed in rabbits, and there were also findings that suggested embryonic/fetal toxicity and abnormal parturition. Considering these serious effects, the classification result was changed.

[Evidence Data]
(1) It was reported that, in a two-generation reproduction toxicity study with rats dosed by feeding, at 2,500 ppm, reduced body weight gain, decreased food consumption, and effects on the liver (hepatocellular hypertrophy, hepatic clear cell change: some appeared from an intermediate dose) were observed in P and F1 male and female parent animals, reduced body weight gain and hepatocellular hypertrophy were observed in F1 and F2 offspring, and reduced litter size and number of pups delivered viable, reduced survival (days 4, 7, and 21 of lactation), and increased number of runt pups were also observed in F2 offspring (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), CLH Report (2015), EPA OPP Human Health Risk Assessment (2013)).
(2) It was reported that, in a developmental toxicity study with rats dosed by gavage (days 6 to 15 of gestation), in parent animals, reduced body weight gain and decreased food consumption were observed in an intermediate (90 mg/kg/day) or higher dose group, and clinical symptoms (ataxia, lethargy, salivation) were also observed in a high dose (360/300 mg/kg/day) group; and in offspring, cleft palate (1/302 animals (0.33%) in an intermediate dose group, 2/285 animals (0.70%) in a high dose group), and non-ossified sternum were observed at an intermediate or higher dose, and visceral abnormalities (short renal papilla, absent renal papilla, dilated ureters) were also observed at a high dose (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), CLH Report (2015)).
(3) In a developmental toxicity study (days 6 to 15 of gestation) by administration of 300 mg/kg/day of this substance to rats to confirm the incidence of cleft palate, marked toxicity such as death (2/189 animals), reduced body weight gain, decreased food consumption, symptoms (ataxia, lethargy, hypoactivity, etc.), etc. were observed in dams of a dose group. In fetuses, lower body weight and reduced number of live fetuses were observed, and the incidence of cleft palate was 0.1%, which was within the range of the background data (0% to 0.35%) of rats of the same strain (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2017)). In the assessment of the EPA on the results of this study, the incidences of cleft palate in a dose group and a control group were observed in 2/2064 fetuses and 0/1222 fetuses respectively. It was reported that, in the background data of the laboratory that conducted the study, the incidence of cleft palate was 0/5431 animals, and the incidence of cleft palate in the preceding test result was confirmed (EPA OPP Human Health Risk Assessment (2013)).
(4) In a developmental toxicity study (days 7 to 19 of gestation) with rabbits dosed by gavage, at 400 mg/kg/day, general toxic effects (reduced body weight gain, decreased food consumption, etc.), abortion or early delivery, and an increase in the total number of dead embryos were observed in parent animals, and skeletal variations (complete formation of the 13th rib) were observed in offspring. It was reported that no teratogenicity was observed (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), CLH Report (2015), EPA OPP Human Health Risk Assessment (2013)).
(5) It was reported that, in a developmental toxicity study (days 6 to 18 of gestation) with rabbits dosed by gavage, at 180 mg/kg/day, sedation was observed in parent animals, and cleft palate was observed in 1 offspring (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2017)).

[Reference Data, etc.]
(6) It was reported that, in a developmental toxicity study with rats dosed by gavage (days 6 to 15 of gestation), at a dose at which marked general toxic effects (death (3/25 animals)) were observed in parent animals, only delayed ossification (phalange and calcanei) was observed in offspring, and no teratogenicity was observed (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2017)).
(7) According to the opinion of the ECHA RAC, cleft palate is a severe toxicity effect that occurs if the critical dose and timing of exposure are conditionally aligned, and it has also been suggested that cleft palates could occur as a consequence of maternal toxicity. It should be noted that cleft palate which was observed in the study with rats appeared with low incidence in two independent studies in (1) and (2) and in different litters, and it should also be noted that cleft palate appeared in the presence of severe maternal toxicity in two studies, but also from a dose at which maternal toxicity was not strong (90 mg/kg/day), following a dose-response pattern (0.33% at 90 mg/kg/day and 0.70% at 300 mg/kg/day). Also, since an increase in the incidence of cleft palate was observed in response to exposure to a pure substance of other triazole pesticide, cleft palate which was observed in rats was judged to be an effect of the administration of this substance. Furthermore, considering that embryonic/fetal resorptions and abortions or early deliveries, which were observed in dams in the developmental toxicity study (3) with rabbits, were also important findings, 1B was proposed as the reproductive toxicant category for this substance (ECHA RAC Opinion (2016)).
(8) In the EU CLP, it was classified in Repr. 1B. (EU-CLP Classification Results (Accessed August 2021)).
8 Specific target organ toxicity - Single exposure Category 1 (systemic)


Danger
H370 P308+P311
P260
P264
P270
P321
P405
P501
[Rationale for the Classification]
Based on (1), deaths were observed within the range for Category 1, and toxic effects were observed also in (2) to (6), and therefore, it was classified in Category 1 (systemic toxicity). Since the findings, which were considered to be neurological symptoms, were considered to be nonspecific findings by the administration in the vicinity of a lethal dose, the nervous system was not adopted as the target organ. Also, it was classified based on the new information source.

[Evidence Data]
(1) It was reported that, in an acute oral neurotoxicity test (GLP) with rats, at 100 mg/kg (within the range for Category 1), piloerection was observed in males, and diarrhea and walking on tiptoe were observed in females; and at 300 mg/kg (within the range for Category 1), hypoactivity and increased/irregular respiratory rate were observed in males and females, gait abnormality, hunched posture, diarrhea, and walking on tiptoe were observed in males, and subnormal temperature, pallor, piloerection, smudge around the nose, soiling and wetness with urine, sedation, prolonged tail flick reflex, and sacrifice in extremis were observed in females (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2017), EPA OPP Human Health Risk Assessment (2013)).
(2) It was reported that, in an acute oral toxicity test with rats (OECD TG 425, GLP), decreased activity, prone position, incoordination, lateral position, piloerection, decreased body temperature, hunched back, and mortalities were observed at 550 mg/kg (within the range for Category 2), and noisy respiration (6 hours after the administration) was observed at 2,000 mg/kg (within the range for Category 2) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2017), CLH Report (2015)).
(3) It was reported that, in an acute oral toxicity test (GLP) with rats, reduced locomotor activity, diarrhea, gait abnormality/crawling/sedation/lateral position/weakness (females), and death (females) were observed at 417 mg/kg (within the range for Category 2); crawling and sedation (males) were observed at 500 mg/kg (within the range for Category 2); gait abnormality and lateral position (males) were observed at 600 mg/kg (within the range for Category 2), lacrimation (males), and death (males) were observed at 720 mg/kg (within the range for Category 2) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2017)).
(4) It was reported that, in an acute oral toxicity test with rats, sedation, dyspnea, ruffled fur, and hunched back were observed at 500 mg/kg (within the range for Category 2), and lateral position, prone position, and death were observed at 1,000 mg/kg (within the range for Category 2) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2017)).
(5) It was reported that, in an acute oral toxicity test (GLP) with mice, reduced motor activity, staggering gait, and crawling/diarrhea (males) were observed at 289 mg/kg (within the range for Category 1); lateral position, prone position (males), and crawling (females) were observed at 347 mg/kg (within the range for Category 2); death and prone position (females) were observed at 417 mg/kg (within the range for Category 2), sedation (females) was observed at 500 mg/kg (within the range for Category 2), and sedation (males) was observed at 600 mg/kg (within the range for Category 2) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2017)).
(6) It was reported that, in an acute oral toxicity study with mice, sedation, dyspnea, ruffled fur, lateral position, hunched back, and death (females) were observed at 800 mg/kg (within the range for Category 2), death (males) was observed at 1,500 mg/kg (within the range for Category 2), and prone position was observed at 2,500 mg/kg (in the range corresponding to "Not classified") (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2017), CLH Report (2015)).
9 Specific target organ toxicity - Repeated exposure Category 2 (liver)


Warning
H373 P260
P314
P501
[Rationale for the Classification]
Based on (1) and (2), hepatocyte lipid deposit, hepatocellular vacuolation, and altered hepatocellular foci were observed, and therefore, it was classified in Category 2 (liver). Besides, since effects on the stomach and intestine which were observed in (7) and (8) were not serious toxic effects and were also not observed in (1) to (5), they were not adopted. Based on the new findings, the classification result was changed.

[Evidence Data]
(1) It was reported that, in a 2-year combined chronic toxicity/carcinogenicity study (OECD TG453, GLP) with rats dosed by feeding, hepatocyte lipid deposit (males) and a decrease in Glu (females) were observed at 500 ppm (18.1 mg/kg/day (males), 23.3 mg/kg/day (females), within the range for Category 2); reduced food consumption, effects on the liver (increased relative weight, hepatocellular hypertrophy, hepatocellular vacuolation (males)), an increase in TP and a decrease in Glu (males), an increase in BUN (females), atrophy of the exocrine pancreas (females) dilatation of the uterus lumen (females), and pulmonary foamy macrophages (females) were observed at 2,500 ppm (96.5 mg/kg/day (males), 131 mg/kg/day (females), within the range for Category 2) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2017)).
(2) It was reported that, in a 2-year carcinogenicity study (OECD TG451, GLP) with mice dosed by feeding, at 500 ppm (49.4 mg/kg/day (males), 55.6 mg/kg/day (females), within the range for Category 2), a decrease in pH of urine and effects on the liver (increased relative weight, hepatocellular hypertrophy, altered hepatocellular foci (eosinophilic)) were observed in males, at 2,500 ppm (344 mg/kg/day (males), 340 mg/kg/day (females), in the range corresponding to "Not classified"); effects on the liver (hepatocellular vacuolation, hepatocyte lipid deposit and dilatation/congestion of the sinusoids, hepatocyte necrosis, chronic inflammation cell infiltration, pigmentation of Kupffer cells) were observed in males and females, decreases in Hb and MCHC, and increases in AST, ALT and ALP were observed in males, and a decrease in pH of urine, and a decrease in Ht were observed in females (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2017)).

[Reference Data, etc.]
(3) It was reported that, in a 90-day oral toxicity test (GLP) with mice dosed by feeding, a decrease in Chol and effects on the liver (increased absolute and relative liver weight, hepatocellular hypertrophy) were observed at 500 ppm (71 mg/kg/day, within the range for Category 2); an increase in SDH and hepatocyte necrosis were observed at 850 ppm (121 mg/kg/day, in the range corresponding to "Not classified"); and an increase in ALT and hepatocellular vacuolation (fatty changes) were observed at 1,450 ppm (199 mg/kg/day, in the range corresponding to "Not classified") (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2017)).
(4) It was reported that, in a 17-week oral toxicity test (GLP) with mice dosed by feeding, effects on the liver (increased absolute and relative liver weight, hepatocellular hypertrophy) (males) were observed at 500 ppm (65 mg/kg/day (males), 85 mg/kg/day (females), within the range for Category 2); a decrease in Chol (males) was observed at 850 ppm (112 mg/kg/day (males), in the range corresponding to "Not classified"); hepatocyte necrosis (males) was observed at 1,450 ppm (194 mg/kg/day (males), in the range corresponding to "Not classified"); and increases in ALT and AST (females), effects on the liver (hepatocellular vacuolation (fatty changes) (males), increased absolute and relative weight (females), hepatocyte hypertrophy and necrosis (females)) were observed at 2,500 ppm (352 mg/kg/day (males), 434 mg/kg/day (females), in the range corresponding to "Not classified") (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2017)).
(5) It was reported that, in an 18-month carcinogenicity study (OECD TG451, GLP) with mice dosed by feeding, hepatocellular hypertrophy was observed at 500 ppm (59 mg/kg/day, within the range for Category 2), and a decrease in Chol, an increase in SDH, and effects on the liver (increased absolute and relative weight, altered hepatocellular foci, hepatocyte necrosis, and pigmentation of Kupffer cells) were observed at 850 ppm (108 mg/kg/day, in the range corresponding to "Not classified") (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2017)).
(6) It was reported that, in a 90-day subacute neurotoxicity test with rats dosed by feeding, no neurological toxicity was observed at 3,500 ppm (males) (222 mg/kg/day, in the range corresponding to "Not classified") or 1,500 ppm (females) (111 mg/kg/day, in the range corresponding to "Not classified") (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)).
(7) It was reported that, in a 21-day dermal toxicity test with rabbits (6 hours/day, 5 days/week), sedation, ruffled fur, tremors, dyspnea, and diarrhea were observed at 1,000 mg/kg/day (converted guidance value: 233 mg/kg/day, in the range corresponding to "Not classified") (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2017)).
(8) It was reported that, in a 90-day oral toxicity study with dogs dosed by feeding, an increase in lymphoid follicle on the mucosal surface of the pylorus of the stomach was observed at 1,250 ppm (35.3 mg/kg/day (males), 35.7 mg/kg/day (females), within the range for Category 2) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2017)).
(9) It was reported that, in a 1-year oral toxicity test (GLP) with dogs dosed by feeding, at 250 ppm (8.4 mg/kg/day (males), 8.9 mg/kg/day (females), within the range for Category 1), congestion of the stomach mucosa, congestion of the duodenal mucosa, congestion of the jejunal mucosa, and congestion of the ileum mucosa were observed in males, and congestion/hemorrhage of the duodenal mucosa were observed in females (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2017)).
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 = 0.51 mg/L for crustacea (Mysidopsis bahia) (EU CLP CLH, 2015, EPA Pesticides RED, 2006, OPP Pesticide Ecotoxicity Database).
11 Hazardous to the aquatic environment Long term (Chronic) Category 1


Warning
H410 P273
P391
P501
It was classified in Category 1 due to being not rapidly degradable (BIOWIN) and 100-day NOEC = 0.068 mg/L for fish (Cyprinodon variegatus) (EU CLP CLH, 2015).
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.

To GHS Information