GHS Classification Results by the Japanese Government

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GENERAL INFORMATION
Item Information
CAS RN 5598-13-0
Chemical Name O-3,5,6-trichloro-2-pyridyl O,O-dimethyl phosphorothioate; Chlorpyrifos-methyl
Substance ID R02-B-053-MHLW, MOE
Classification year (FY) FY2020
Ministry who conducted the classification Ministry of Health, Labour and Welfare (MHLW)/Ministry of the Environment (MOE)
New/Revised Revised
Classification result in other fiscal year FY2006  
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. It was classified as "Not classified."
2 Flammable gases Not classified (Not applicable)
-
-
- - Solid (GHS definition). It was classified as "Not classified."
3 Aerosols Not classified (Not applicable)
-
-
- - Not aerosol products. It was classified as "Not classified."
4 Oxidizing gases Not classified (Not applicable)
-
-
- - Solid (GHS definition). It was classified as "Not classified."
5 Gases under pressure Not classified (Not applicable)
-
-
- - Solid (GHS definition). It was classified as "Not classified."
6 Flammable liquids Not classified (Not applicable)
-
-
- - Solid (GHS definition). It was classified as "Not classified."
7 Flammable solids Classification not possible
-
-
- - No data available. Besides, there is information that it is combustible (GESTIS (Access on May 2020)).
8 Self-reactive substances and mixtures Classification not possible
-
-
- - There is a chemical group associated with self-reactive properties (P-O) present in the molecule, but the classification is not possible due to no data.
9 Pyrophoric liquids Not classified (Not applicable)
-
-
- - Solid (GHS definition). It was classified as "Not classified."
10 Pyrophoric solids Classification not possible
-
-
- - No data available.
11 Self-heating substances and mixtures Classification not possible
-
-
- - Classification is not possible because test methods applicable to solid (melting point <= 140 deg C) substances are not available.
12 Substances and mixtures which, in contact with water, emit flammable gases Not classified
-
-
- - It contains a metalloid (P), but it was classified as "Not classified" because it is estimated that it does not react vigorously with water from water solubility data of 4.76 mg/L (20 deg C) (HSDB (Access on May 2020)).
13 Oxidizing liquids Not classified (Not applicable)
-
-
- - Solid (GHS definition). It was classified as "Not classified."
14 Oxidizing solids Classification not possible
-
-
- - The substance is an organic compound containing chlorine and oxygen (but not fluorine), and the oxygen is chemically bonded to the element other than carbon or hydrogen (P). However, the classification is not possible due to no data.
15 Organic peroxides Not classified (Not applicable)
-
-
- - Organic compounds containing no bivalent -O-O- structure in the molecule. It was classified as "Not classified."
16 Corrosive to metals Classification not possible
-
-
- - It is a solid with a melting point of 55 deg C or lower, but the classification is not possible due to no data.
17 Desensitized explosives Not classified (Not applicable)
-
-
- - There are no chemical groups associated with explosive properties present in the molecule. It was classified as "Not classified."

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]
It was classified in Category 4 from (1) - (3).

[Evidence Data]
(1) LD50 for rats: 1,500 mg/kg (HSDB (Access on May 2020))
(2) LD50 for rats: 1,830 mg/kg (GESTIS (Access on May 2020))
(3) LD50 for rats: 3,000 mg/kg (IPCS PIM G001 (1998))
1 Acute toxicity (Dermal) Not classified
-
-
- - [Rationale for the Classification]
It was classified as "Not classified" from (1), (2).

[Evidence Data]
(1) LD50 for rabbits: > 2,000 mg/kg (GESTIS (Access on May 2020))
(2) LD50 for rats: 3,713 mg/kg (HSDB (Access on May 2020))
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]
The category could not be determined from (1), and it was classified as "Classification not possible."
Besides, a reference value in the unit of mg/L was applied as dust.

[Evidence Data]
(1) LC50 for rats (4 hours): > 0.67 mg/L (maximal technically achievable concentration) (JMPR (2009), GESTIS (Access on May 2020), HSDB (Access on May 2020))
(2) Vapor pressure of this substance: 0.0000225 mmHg (25 deg C) (HSDB (Access on May 2020)) (converted value for the saturated vapor pressure concentration: 0.00039 mg/L)
(3) This knowledge was from a test on vapor generated at 55 deg C by using Reldan F, a formulation containing 97% of chlorpyrifos-methyl, without a medium (JMPR (2009)). Besides, the melting point of this substance was about 45 deg C.
2 Skin corrosion/irritation Not classified
-
-
- - [Rationale for the Classification]
It was classified as "Not classified" from (1), (2).

[Evidence Data]
(1) This substance was a slight transient irritant to the rabbit skin (JMPR (2009), HSDB (Access on May 2020)).
(2) In a skin irritation test by 4-hour occlusive application of this substance (500 mg) to the rabbit skin, very slight
reddening was observed and vanished within 24 hours after the application (GESTIS (Access on May 2020)).
3 Serious eye damage/eye irritation Not classified
-
-
- - [Rationale for the Classification]
It was classified as "Not classified" from (1), (2).

[Evidence Data]
(1) This substance was a slight transient irritant to the rabbit eye (JMPR (2009), HSDB (Access on May 2020)).
(2) In a test by 72-hour exposure of the rabbit eye to this substance (100 mg), only slight conjunctivitis was observed and disappeared within 24 hours after the application (GESTIS (Access on May 2020)).
4 Respiratory sensitization Classification not possible
-
-
- - [Rationale for the Classification]
Classification not possible due to lack of data.
4 Skin sensitization Classification not possible
-
-
- - [Rationale for the Classification]
There was a description of (1), but it was classified as "Classification not possible" due to lack of data. Because positive and negative data were mixed, and it was impossible to confirm the details, the classification result was changed.

[Reference Data, etc.]
(1) In skin sensitization tests with guinea pigs, this substance was reported to be negative in a Buehler test and positive in a maximization test (JMPR (2009), HSDB (Access on May 2020)).
5 Germ cell mutagenicity Not classified
-
-
- - [Rationale for the Classification]
It was classified as "Not classified" from (1), (2).

[Evidence Data]
(1) As for in vivo, it was reported to be negative in a micronucleus test with mouse bone marrow cells and an unscheduled DNA synthesis test with rats (JMPR (2009)).
(2) As for in vitro, it was reported to be negative in a bacterial reverse mutation test and a gene mutation test with hamster ovary cells. And it was reported to be positive (S9+) and negative (S9-) in a chromosomal aberration test with hamster ovary cells (JMPR (2009)).
6 Carcinogenicity Not classified
-
-
- - [Rationale for the Classification]
There was no available report in humans. It was classified as "Not classified" from (1), (2).

[Evidence Data]
(1) As for classification results by domestic and international organizations, EPA classified it in NL (Not Likely to be Carcinogenic to Humans) (EPA Annual Cancer Report 2018 (Access on July 2020): classified in 1999).
(2) In combined chronic toxicity/carcinogenicity tests by diet administration of this substance to male and female mice for 18 months and male and female rats for 2 years, no treatment-related increase in tumor incidences was observed in either species (JMPR (2009)).
7 Reproductive toxicity Category 2


Warning
H361 P308+P313
P201
P202
P280
P405
P501
[Rationale for the Classification]
Based on (1) to (3), a comprehensive judgment was made and this substance was classified in Category 2. The information sources used for the previous classification could not be used, and a different information source was used for the classification study. Therefore, the classification results were changed from the previous classification.

[Evidence Data]
(1) In a developmental toxicity study by oral administration to female mice on days 7 to 13 of gestation, there was no description of maternal toxicity, but lower fetal body weight, an increased incidence of cleft palate, and a delay of ossification of the cervical vertebral body were observed (JMPR (1975)).
(2) In a developmental toxicity study with female mice dosed with a single oral dose of 1,000 mg/kg on day 7 or 10 of gestation, skeletal abnormalities (exencephalia, cleft palate, liberation of bone fragment of cervical vertebral arch) were observed in a few cases after administration on the seventh day of gestation. No control group was presented in this study (JMPR (1975)).
(3) In a developmental toxicity study with female rats on days 6 to 15 of gestation (no description of the administration route), at a dose at which decreases in plasma and erythrocyte cholinesterase (ChE) activity were observed in dams, an increase in lumbar spines and a decrease in ChE activity in a homogenate of fetal tissues were observed in fetuses, and at lower doses, delayed ossification of the sternebrae in fetuses was observed (JMPR (1975)).

[Reference Data, etc.]
(4) In a three-generation reproduction toxicity study with rats dosed by feeding, at a dose at which inhibition of plasma and erythrocyte ChE activity was observed in parental animals, no reproductive toxicity effects were observed. Lower body weight was observed in pups in the third generation (days 0, 4 and 21 postpartum) (JMPR (1975)).
8 Specific target organ toxicity - Single exposure Category 2 (nervous system)


Warning
H371 P308+P311
P260
P264
P270
P405
P501
[Rationale for the Classification]
This substance is an organophosphorus pesticide. Although there was no data of this substance, this substance was considered to have an inhibitory action on cholinesterase activity. Therefore, it was classified in Category 2 (nervous system).

[Reference Data, etc.]
(1) Exposure to organophosphorus pesticides, including this substance, in humans caused muscarinic manifestations (increased bronchial secretion, excessive sweating, salivation, lachrymation, pinpoint pupils, bronchoconstriction, abdominal cramps (vomiting and diarrhea), bradycardia), nicotinic manifestations (fasciculation of fine muscles, tachycardia), and central nervous system manifestations (headache, dizziness, restlessness, anxiety, mental confusion, convulsions, coma, depression of the respiratory center). Mild poisoning might only include muscarinic and nicotinic signs. Severe cases showed central nervous system involvement. The combination of the above-mentioned symptoms caused respiratory failure, sometimes leading to pulmonary edema (EHC 63 (1986)).
(2) Organophosphorus pesticides, such as this substance, are absorbed by all routes, including inhalation, ingestion, and dermal absorption. The toxicological effects of the organophosphorus pesticides are due to the inhibition of acetylcholinesterase in the nervous system, resulting in respiratory, myocardial and neuromuscular transmission impairment (IPCS PIM G001 (1998)).
9 Specific target organ toxicity - Repeated exposure Category 1 (nervous system, adrenal gland)


Danger
H372 P260
P264
P270
P314
P501
[Rationale for the Classification]
Based on (2), in a dermal application to humans, plasma cholinesterase (ChE) activity inhibition was observed. Based on (3) to (6), in an oral administration to experimental animals, effects on the nervous system and adrenal gland were observed at doses within the range for Category 1. Based on (7), in a dermal application to experimental animals, effects on the nervous system were observed at doses within the range for Category 1 and effects on the adrenal gland were observed at doses within the range for Category 2. Therefore, it was classified in Category 1 (nervous system, adrenal gland). In (5), effects on the kidney, muscle, and blood system were also observed at doses within the range for Category 2, but they were considered to be findings associated with decreased food consumption and decreased body weight, and in the longer-term test of (6), no effects on these organs were observed. Therefore, they were not adopted as the target organs. The information from a new source was examined, and the classification results were changed from the previous classification.

[Evidence Data]
(1) Organophosphorus pesticides, such as this substance, are absorbed by all routes, including inhalation, ingestion, and dermal absorption. The toxicological effects of the organophosphorus pesticides are due to the inhibition of acetylcholinesterase in the nervous system, resulting in respiratory, myocardial and neuromuscular transmission impairment (IPCS PIM G001 (1998)).
(2) This substance was dermally administered to the dorsal and abdominal skin of three volunteers at 10, 25, and 50 mg/kg/day and plasma and erythrocyte ChE activities were measured. As a result, no clinical symptoms of toxicity were noted and plasma ChE activity was slightly depressed in the group administrated at 10 mg/kg/day from day 10. The effect became maximal on day 12 and regressed by day 25. In the group administrated at 25 mg/kg/day, plasma ChE activity decreased by 47.5% on day 4 and regressed by day 28 (JMPR (2009)).
(3) In a 13-week oral toxicity test with rats dosed by feeding, a decrease in plasma ChE activity was observed at or above 1 mg/kg/day (within the range for Category 1), and decreases in erythrocyte and brain ChE activity, bilateral diffuse hypertrophy of the adrenal gland, and vacuolation of the adrenal cortex zona fasciculata were observed at or above 10 mg/kg/day (within the range for Category 1) (JMPR (2009).
(4) In a two-year oral toxicity test with rats dosed by feeding, at or above 1 mg/kg/day (within the range for Category 1), a decrease in plasma ChE activity was observed in males and females; and at 50 mg/kg/day (within the range for Category 2), decreases in erythrocyte and brain ChE activity and vacuolation of the adrenal cortex zona fasciculata in males and females, and an increase in testicular weight and hyperplasia of Leydig cells in males were observed (JMPR (2009)).
(5) In a 13-week oral toxicity test of this substance with dogs dosed by feeding, at or above 0.1 mg/kg/day (within the range for Category 1), decreases in plasma and erythrocyte ChE activity were observed; and at 50 mg/kg/day (within the range for Category 2), a decrease in food consumption, a decrease in body weight, decreases in red blood cell count, packed cell volume, and hemoglobin concentration, increases in liver and kidney weight, increases in ALP, AST, and CK, a decrease in brain ChE activity, and diffuse centrilobular hepatocyte hypertrophy were observed in males and females, and muscle wasting, a decrease in mesenteric fat, skeletal muscle atrophy, and vacuolation of the renal proximal tubules were observed in females (JMPR (2009)).
(6) In a 104-week oral toxicity test of this substance with dogs dosed by feeding, a decrease in plasma ChE activity was observed at or above 0.1 mg/kg/day (within the range for Category 1); a decrease in erythrocyte ChE activity was observed at or above 1 mg/kg/day (within the range for Category 1); and neurological examinations revealed abnormalities (reaction to sensation and segmental reflex) at 3 mg/kg/day (within the range for Category 1). No dose-related effects on hematological, biochemical, or urinalysis parameters were indicated (JMPR (2009)).
(7) This substance was dermally administered to rats for 28 days to evaluate systemic effects. As a result, inhibition of plasma, erythrocyte, and heart ChE activity in males and females and inhibition of brain ChE activity in females were observed at or above 10 mg/kg/day (converted equivalent value: 3.1 mg/kg/day (within the range for Category 1)); inhibition of brain ChE activity, an increase in adrenal weight, and vacuolation of the adrenal cortex were observed in males at or above 100 mg/kg/day (converted equivalent value: 31 mg/kg/day (within the range for Category 2)); and an increase in adrenal weight and vacuolation of the adrenal cortex were observed in females at 300 mg/kg/day (exceeding Category 2) (JMPR (2009)).
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 48-hour LC50 = 0.000028 mg/L for crustacea (Penaeus duorarum) (ECOTOX, 2020, EPA OPP Pesticide Ecotoxicity Database, 2020).
11 Hazardous to the aquatic environment Long term (Chronic) Category 1


Warning
H410 P273
P391
P501
Reliable chronic toxicity data were not obtained. It was classified in Category 1 because it is not rapidly degradable (BIOWIN), and it was classified in Category 1 in acute toxicity.
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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