GHS Classification Result

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GENERAL INFORMATION
Item Information
CAS RN 2921-88-2
Chemical Name O,O-diethyl O-(3,5,6-trichloro-2-pyridyl) thiophosphate [Chlorpyrifos]
Substance ID H29-B-020
Classification year (FY) FY2017
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 (FY2013 revised edition (Ver. 1.1))
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) 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 applicable
-
-
- - There are no chemical groups associated with explosive properties present in the molecule.
2 Flammable gases (including chemically unstable gases) Not applicable
-
-
- - Solid (GHS definition).
3 Aerosols Not applicable
-
-
- - Not aerosol products.
4 Oxidizing gases Not applicable
-
-
- - Solid (GHS definition).
5 Gases under pressure Not applicable
-
-
- - Solid (GHS definition).
6 Flammable liquids Not applicable
-
-
- - Solid (GHS definition).
7 Flammable solids Classification not possible
-
-
- - It is described that it is combustible (ICSC (J) (2014)), but the classification is not possible due to no data.
8 Self-reactive substances and mixtures Not applicable
-
-
- - There are no chemical groups present in the molecule associated with explosive or self-reactive properties.
9 Pyrophoric liquids Not applicable
-
-
- - Solid (GHS definition).
10 Pyrophoric solids Classification not possible
-
-
- - No data available.
11 Self-heating substances and mixtures Classification not possible
-
-
- - 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 metalloids (P), but it is estimated that it does not react vigorously with water from the measurement data of water solubility of 1.4 mg/L (25 deg C) (HSDB (Access on June 2017)).
13 Oxidizing liquids Not applicable
-
-
- - Solid (GHS definition).
14 Oxidizing solids Classification not possible
-
-
- - No data available.
15 Organic peroxides Not applicable
-
-
- - There is no bivalent -O-O- structure in the molecule.
16 Corrosive to metals Classification not possible
-
-
- - There is the information that it is a substance with melting point of <= 55 deg C and attacks copper and brass (ICSC (J) (2014)), but the classification is not possible due to no data.

HEALTH HAZARDS
Hazard class Classification Pictogram
Signal word
Hazard statement
(code)
Precautionary statement
(code)
Rationale for the classification
1 Acute toxicity (Oral) Category 3


Danger
H301 P301+P310
P264
P270
P321
P330
P405
P501
Based on six reports of LD50 values of 82 mg/kg (females) (ATSDR (1997)), 118 mg/kg (males) (ATSDR (1997)), 135 mg/kg (females) (ATSDR (1997), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2011)), 155 mg/kg (females and males) (ATSDR (1997)), 163 mg/kg (males) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2011)), and 223 mg/kg (females and males) (EPA Pesticide (2006)), it was classified in Category 3.
1 Acute toxicity (Dermal) Not classified
-
-
- - There are two reports of LD50 values for rats of 202 mg/kg (ATSDR (1997), ACGIH (7th, 2003), EPA Pesticide (2006)) and > 2,000 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2011)). Although one value corresponds to Category 3, and the other corresponds to "Not classified," this substance was classified as "Not classified" by adopting the data from a GLP-compliant test in the Risk Assessment Report by the Food Safety Commission of Japan.
1 Acute toxicity (Inhalation: Gases) Not applicable
-
-
- - Solid (GHS definition)
1 Acute toxicity (Inhalation: Vapours) Not applicable
-
-
- - Solid (GHS definition)
1 Acute toxicity (Inhalation: Dusts and mists) Classification not possible
-
-
- - Classification not possible due to lack of data. Besides, an LC50 value of 0.2 mg/L for rats was reported (EPA Pesticide (2006), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2011)). This data might be based on aerosols because this substance is a solid. A category cannot be determined on the basis of this data alone. Therefore, it was classified as "Classification not possible."
2 Skin corrosion/irritation Not classified
-
-
- - Based on a report that this substance was slightly irritating in a skin irritation test with rabbits, and the irritation resolved within 7 days (EPA Pesticide (2006), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2011)), it was classified as "Not classified" (Category 3 in the UN GHS classification).
3 Serious eye damage/eye irritation Category 2B
-
Warning
H320 P305+P351+P338
P337+P313
P264
Based on a report that this substance was slightly irritating in an eye irritation test with rabbits, and the irritation resolved within 24 hours (EPA Pesticide (2006), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2011)), this substance was classified in Category 2B. This substance was reclassified on the basis of data newly obtained from this survey.
4 Respiratory sensitization Classification not possible
-
-
- - Classification not possible due to lack of data.
4 Skin sensitization Classification not possible
-
-
- - It was reported that this substance was not sensitizing in a skin sensitization test with guinea pigs based on the Buehler method (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2011)). However, since only one case is reported, this substance was classified as "Classification not possible," and the category was revised.
5 Germ cell mutagenicity Classification not possible
-
-
- - The substance was classified as "Classification not possible" because it was not possible to classify a substance as "Not classified" according to the revised GHS classification guidance for the Japanese Government. As for in vivo, there are reports of negative and positive results from mouse bone marrow cell micronucleus tests (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2011), ATSDR (1997)), but reproducibility of the positive finding has not been established. As for in vitro data, a bacterial reverse mutation test and a chromosomal aberration test and a sister chromatid exchange test with mammalian cultured cells were all negative (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2011), ATSDR (1997), NTP DB (Access on May 2017)).
6 Carcinogenicity Classification not possible
-
-
- - No carcinogenicity was observed in either a 2-year feeding study with rats, an 18-month feeding study with mice, or a 2-year feeding study with mice (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2011)). As for classifications by other organizations, this substance was classified by the ACGIH in A4 (ACGIH (7th, 2003), proposed in 1995) and by the EPA in Group E (Evidence of Non-Carcinogenicity for Humans) (Chemicals Evaluated for Carcinogenic Potential: Annual Cancer Report (2016), evaluated in 1993). From the above, in accordance with the GHS classification guidance for the Japanese government, this substance was classified as "Classification not possible" on the basis of the classification result by the ACGIH, which proposed a carcinogenic classification more recently.
7 Reproductive toxicity Classification not possible
-
-
- - In a two-generation study with rats dosed by feeding, inhibition of erythrocyte cholinesterase activity was found in the parental animals at or above 1 mg/kg/day, but no adverse effects on reproduction in the parental animals were observed at up to the highest dose of 5 mg/kg/day. However, in the pups, a decrease in the survival rate and reduced body-weight gain were observed at 5 mg/kg/day (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2011), PATTY (6th, 2012), ACGIH (7th, 2003)). Meanwhile, in developmental toxicity tests in which pregnant rats, pregnant mice, or pregnant rabbits were dosed by gavage during the organogenesis period, reduced body-weight gain was observed in the dams at 15 mg/kg/day for rats, at 10 mg/kg/day for mice, and at 140 mg/kg/day for rabbits. However, effects on the fetuses were limited: there were either no effects or only minor findings related to reduced body weights, even at maternally toxic doses or above (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2011), PATTY (6th, 2012), ACGIH (7th, 2003)). In another study, pregnant rats were dosed by gavage (from days 6-20 of pregnancy) to examine effects on the development of the nervous system in offspring. While erythrocyte cholinesterase inhibition occurred in the dams at or above 0.3 mg/kg/day, the pups showed only effects of reduced body weight but no developmental neurotoxicity at 5.0 mg/kg/day (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2011)). From the above, clear reproductive/developmental effects which should be adopted as rationale for classification were generally not observed, even at parentally toxic doses, but in the two-generation study with rats, a reduced survival rate of pups was observed even at 5 mg/kg/day, which was the highest dose but is still a rather low dose. In addition, it was considered that information was lacking on whether reproductive/developmental effects occurred when higher doses were administered. Therefore, this substance was classified as "Classification not possible."
8 Specific target organ toxicity - Single exposure Category 1 (nervous system)


Danger
H370 P308+P311
P260
P264
P270
P321
P405
P501
This substance is an organophosphorus insecticide and inhibits acetylcholinesterase (ATSDR (1997), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2011)).
In humans, multiple cases were reported which showed coma, seizure-like motor activity, miosis, muscle spasms and fasciculation, hyperreflexia or hyporeflexia, lacrimation, salivation, sweating, bronchorrhea, and athetosis by acute oral exposure to this substance by accident or attempted suicide (ATSDR (1997)). As for symptoms of acute inhalation exposure in humans, paresthesia, dizziness, and headache are reported (ATSDR (1997)). As for experimental animals, in tests with rats given single oral doses of 60-100 mg/kg, which correspond to Category 1, it is reported that hypoactivity, ataxia, tremors, and hypothermia were observed, and that brain, plasma, and erythrocyte cholinesterase activities were reduced (ACGIH (7th, 2003)). From the above, this substance was classified in Category 1 (nervous system).
9 Specific target organ toxicity - Repeated exposure Category 1 (nervous system, adrenal gland), Category 2 (eye, haemal system, liver)


Danger
Warning
H372
H373
P260
P264
P270
P314
P501
In humans, blurred vision, flushing of the skin, and decreased urination were reported among pet-control employees who used this substance within 3 months; fatigue, dizziness, difficulty in concentrating, memory problems, depression, and headache were reported among workers who applied termiticide of this substance and were exposed for an average of 0.4 years (PATTY (6th, 2012)).
As for experimental animals, 90-day repeated oral dose toxicity tests with rats or mice dosed by feeding were conducted. The rats exhibited the following: inhibition of erythrocyte cholinesterase activity (20% or more) at or above 1.0 mg/kg/day, which is within the guidance value range for Category 1; inhibition of brain cholinesterase activity and vacuolization in the zona fasciculata in the adrenal gland at or above 5.0 mg/kg/day; and decreases in erythrocyte count, hematocrit values, etc. at 15 mg/kg/day, which is within the guidance value range for Category 2. The mice exhibited inhibition of brain cholinesterase activity at or above 50 ppm (7.5 mg/kg/day), which is within the guidance value range for Category 1; adrenal fatty pigmentation at or above 200 ppm (30 mg/kg/day), which is within the guidance value range for Category 2; and increased mortality, opacity of the eyeball, and acute or subacute keratitis at or above 400 ppm (60 mg/kg/day) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2011)). In addition, it is reported that in a two-year repeated oral dose toxicity test with rats dosed by feeding, inhibition of erythrocyte cholinesterase activity was observed at or above 1.0 mg/kg/day, which is within the guidance value range for Category 1. Decreases in total cholesterol, total protein, and globulin; inhibition of brain cholinesterase activity; and fatty vacuolization in the zona fasciculata of the adrenal cortex, etc. were observed at 10 mg/kg/day. In an 18-month repeated oral dose toxicity test with mice dosed by feeding, inhibition of erythrocyte and brain cholinesterase activities were found at or above 50ppm (males: 6.1-12 mg/kg/day, females: 6.6-12 mg/kg/day), which is within the guidance value range for Category 1 or near the upper bound thereof. Opacity of the eyeball; salivation; and mild subacute cholangitis, histiocytic hyperplasia, and centrilobular hepatocyte fatty vacuolization in the liver were observed at 250 ppm, which is within the guidance value range for Category 2 (males: 32-55 mg/kg/day, females: 34-62 mg/kg/day) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2011)).
From the above, this substance was classified in Category 1 (nervous system, adrenal gland), Category 2 (eye, haemal system, liver).
Classification based on a new information source resulted in a change in the classification result.
10 Aspiration hazard Classification not possible
-
-
- - 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 (Acute) Category 1


Warning
H400 P273
P391
P501
From 48-hour LC50 = 0.000035 mg/L for crustacea (Daphnia ambigua) (Environmental Risk Assessment for Chemical Substances vol. 8 (Ministry of the Environment, 2010)), it was classified in Category 1.
11 Hazardous to the aquatic environment (Long-term) Category 1


Warning
H410 P273
P391
P501
Due to being not rapidly degradable (non-biodegradable, a degradation rate by BOD: 0.2% (J-CHECK, 1979)), and 32-day NOEC (reproduction inhibition) = 0.000045 mg/L for crustacea (Ceriodaphnia cf. dubia) (Environmental Risk Assessment for Chemical Substances vol. 8 (Ministry of the Environment, 2010)), it was classified in Category 1.
12 Hazardous to the ozone layer Classification not possible
-
-
- - No data available.


NOTE:
* A blank or "-" in a cell of classification denotes that the classification of the hazard class was not conducted.
* Hazard_statement_and/or_Precautionary_statement will show when hovering the mouse over a code of Hazard_statement_and/or_Precautionary_statement.
Hazard_statement_and/or_Precautionary_statement are also provided in the Excel file.
* Classification was conducted by relevant Japanese Ministries in accordance with GHS Classification Guidance for the Japanese Government,
and is intended to provide a reference for preparing GHS labelling and SDS for users.
* This is a provisional English translation of classification results and is subject to revision without notice.
* The responsibility for any resulting GHS labelling and SDS referenced from this site is with users.
* Codes assigned to each of the hazard statements and codes for each of the precautionary statement are
based on the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) in United Nations.

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