GHS Classification Results by the Japanese Government

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GENERAL INFORMATION
Item Information
CAS RN 1910-42-5
Chemical Name 1,1-Dimethyl-4,4-bipyridinium dichloride; Paraquat dichloride
Substance ID R01-B-058
Classification year (FY) FY2019
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) 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 *
-
-
- - There are no chemical groups associated with explosive properties present in the molecule. It was classified as "Not classified (Not applicable)."
2 Flammable gases *
-
-
- - Solid (GHS definition). It was classified as "Not classified (Not applicable)."
3 Aerosols *
-
-
- - Not aerosol products. It was classified as "Not classified (Not applicable)."
4 Oxidizing gases *
-
-
- - Solid (GHS definition). It was classified as "Not classified (Not applicable)."
5 Gases under pressure *
-
-
- - Solid (GHS definition). It was classified as "Not classified (Not applicable)."
6 Flammable liquids *
-
-
- - Solid (GHS definition). It was classified as "Not classified (Not applicable)."
7 Flammable solids *
-
-
- - It was classified as "Not classified" from information that it is not combustible (Hommel (1991)).
8 Self-reactive substances and mixtures *
-
-
- - There are no chemical groups present in the molecule associated with explosive or self-reactive properties. It was classified as "Not classified (Not applicable)."
9 Pyrophoric liquids *
-
-
- - Solid (GHS definition). It was classified as "Not classified (Not applicable)."
10 Pyrophoric solids *
-
-
- - It was classified as "Not classified" from information that it is not combustible (Hommel (1991)).
11 Self-heating substances and mixtures *
-
-
- - It was classified as "Not classified" from information that it is not combustible (Hommel (1991)).
12 Substances and mixtures which, in contact with water, emit flammable gases *
-
-
- - The chemical structure of the substance does not contain metals or metalloids (B, Si, P, Ge, As, Se, Sn, Sb, Te, Bi, Po, At). It was classified as "Not classified (Not applicable)."
13 Oxidizing liquids *
-
-
- - Solid (GHS definition). It was classified as "Not classified (Not applicable)."
14 Oxidizing solids *
-
-
- - The substance is an organic compound containing chlorine (but not fluorine or oxygen), which is chemically bonded only to nitrogen, carbon, or hydrogen. Because the chlorine is ionically bonded to nitrogen and is estimated to not contribute to oxidization, it was classified as "Not classified (Not applicable)."
15 Organic peroxides *
-
-
- - Organic compounds containing no bivalent -O-O- structure in the molecule. It was classified as "Not classified (Not applicable)."
16 Corrosive to metals *
-
-
- - Classification is not possible because test methods applicable to solid substances are not available.
17 Desensitized explosives *
-
-
- - 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 3


Danger
H301 P301+P310
P264
P270
P321
P330
P405
P501
[Rationale for the Classification]
Based on (1)-(6), it was classified in Category 3.

[Evidence Data]
(1) LD50 for rats: 100 mg/kg (ACGIH (7th, 2018))
(2) LD50 for rats: 126 mg/kg, 200 mg/kg, male: 110 mg/kg, female: 100 mg/kg (EHC 39 (1984))
(3) LD50 for rats: male: 344 mg/kg, female: 283 mg/kg (EPA Pesticide (1997))
(4) LD50 for rats: about 150 mg/kg (IPCS, PIM 399 (2000))
(5) LD50 for rats: 100-300 mg ion/kg (converted value: 138.1-414.2 mg/kg) (JMPR (2003))
(6) LD50 for rats: male: 223 mg/kg, female: 258 mg/kg (Japanese Journal of Pesticide Science vol, 13 No. 1 (Pesticide Science Society of Japan, 1988))
1 Acute toxicity (Dermal) Category 2


Danger
H310 P302+P352
P361+P364
P262
P264
P270
P280
P310
P321
P405
P501
[Rationale for the Classification]
Based on (1)-(3), it was classified in Category 2.

[Evidence Data]
(1) LD50 for rats: male: 115 mg/kg, female: 79 mg/kg (Japanese Journal of Pesticide Science vol. 13 No. 1 (Pesticide Science Society of Japan, 1988))
(2) LD50 for rats: 350 mg/kg, male: 80 mg/kg, female: 90 mg/kg (EHC 39 (1984))
(3) LD50 for rats: 80-660 mg ion/kg (converted value: 110.4-911.2 mg/kg) (JMPR (2003))

[Reference Data, etc.]
(4) LD50 for rats: >2,000 mg/kg (EPA Pesticide (1997))
(5) LD50 for rabbits: 236 mg/kg, 240 mg/kg, 500 mg/kg (EHC 39 (1984))
(6) LD50 for rabbits: >480 mg/kg (IPCS, PIM 399 (2000))
1 Acute toxicity (Inhalation: Gases) *
-
-
- - [Rationale for the Classification]
Solid (GHS definition). It was classified as "Not classified (Not applicable)."
1 Acute toxicity (Inhalation: Vapours) *
-
-
- - [Rationale for the Classification]
Classification not possible due to lack of data.
1 Acute toxicity (Inhalation: Dusts and mists) Category 1


Danger
H330 P304+P340
P403+P233
P260
P271
P284
P310
P320
P405
P501
[Rationale for the Classification]
Based on (1), (2), it was classified in Category 1.
Besides, since exposure concentrations are higher than the saturated vapour concentration (1.2 * 10-6 mg/L), the reference value in units of mg/L was applied as the dust.

[Evidence Data]
(1) LC50 (6 hours, the dust) for rats: 1 microg/L (0.001 mg/L) (converted 4-hour equivalent value: 0.0015 mg/L) (EPA Pesticide (1997))
(2) LC50 (4 hours) for rats: 0.0006-0.0014 mg ion/L (converted value: 0.00083-0.00193 mg/L) (JMPR (2003))
2 Skin corrosion/irritation Category 2


Warning
H315 P302+P352
P332+P313
P362+P364
P264
P280
P321
[Rationale for the Classification]
Based on (1) and (2), it was classified in Category 2.

[Evidence Data]
(1) In a skin irritation test (4-hour application) with rabbits, very slight erythema and edema, and desquamation and thickening, etc. were observed, with regression times of 2-3 days (2 animals) or 27 days (1 animal) for erythema, 7 days for edema, and 34 days for other signs (EPA Pesticide (1997)).
(2) This substance, in concentrated forms, is irritating to the skin, and the effects might be prolonged (IPCS, PIM 399 (2000)).

[Reference Data, etc.]
(3) In fatalities attributed to occupational exposure to this substance, irritation and ulceration of the skin occurred within 3 days (ACGIH (7th, 2018)).
(4) This substance can cause minimal to mild irritation when applied directly to the skin (ACGIH (7th, 2018)).
(5) It was classified as "Skin Irrit. 2 (H315)" in the EU CLP classification (EU CLP classification (Access on July 2019)).
3 Serious eye damage/eye irritation Category 1


Danger
H318 P305+P351+P338
P280
P310
[Rationale for the Classification]
Based on (1) and (2), it was classified in Category 1. The category was changed because new data were obtained.

[Evidence Data]
(1) In an eye irritation test with rabbits, effects on the cornea and the conjunctiva were seen, and the effect on the cornea cleared by Day 17, but among the effects on the conjunctiva, regression of redness took 28 days, and discharge was still present after Day 28 (EPA Pesticide (1997)).
(2) Concentrated splashes of this substance may cause severe eye irritation which resulted in corneal and conjunctival damages. The corneal effect persisted for up to 3 to 4 weeks with temporary blurring of vision (IPCS, PIM 399 (2000)).

[Reference Data, etc.]
(3) In an eye irritation test with 3 rabbits by application this substance (as paraquat ions, 33%), slight to moderate corneal opacity was seen with this effect resolving within 17 days. Redness and chemosis of the conjunctiva were seen in all animals and these resolved by 28 days and 14 days after exposure (JMPR (2003)). In fatalities attributed to occupational exposure to this substance, irritation and ulceration of the skin occurred within 3 days (ACGIH (7th, 2018)).
(4) It was classified as "Eye Irrit. 2 (H319)" in the EU CLP classification (EU CLP classification (Access on July 2019)).
4 Respiratory sensitization *
-
-
- - [Rationale for the Classification]
Classification not possible due to lack of data.
4 Skin sensitization *
-
-
- - [Rationale for the Classification]
Based on (1) and (2), it was classified as "Not classified."

[Evidence Data]
(1) In a skin sensitization test with guinea pigs, this substance failed to induce a positive response (ACGIH (7th, 2001)).
(2) In a skin sensitization test with guinea pigs (maximization test), it was concluded that this substance (as paraquat ions, 33%) had no sensitization potential (EPA Pesticide (1997), JMPR (2003)).
5 Germ cell mutagenicity *
-
-
- - [Rationale for the Classification]
Based on (1) and (2), it was classified as "Not classified."

[Evidence Data]
(1) As for in vivo, there are reports of it being negative in a dominant lethal test and a micronucleus test with mice, and a hepatocyte unscheduled DNA synthesis test and a bone marrow chromosomal aberration test with rats (EHC 39 (1984), IRIS (1987), EPA Pesticide (1997), JMPR (2003)).
(2) As for in vitro, there were reports that it was negative in a bacterial reverse mutation test, and a micronucleus test with cultured mammalian cells and an unscheduled DNA synthesis test with rat hepatocytes and positive or negative in a mouse lymphoma test and a chromosomal aberration test with cultured mammalian cells (IRIS (1987), EPA Pesticide (1997), JMPR (2003), NTP DB (Access on July 2019)). However, the positive results in the chromosomal aberration test and the micronucleus test are believed to be secondary to superoxide anion production from the reduction and oxidation of this substance (ACGIH (7th, 2018)).

[Reference Data, etc.]
(3) This substance was found to have minimal to no genotoxic activity when evaluated in a variety of in vitro and in vivo test systems. It is reported that positive results were limited to in vitro tests, and its genotoxicity was accompanied by high cytotoxicity (EHC 39 (1984)).
6 Carcinogenicity *
-
-
- - [Rationale for the Classification]
From the latest classification results by other organizations in (1), it was classified as "Classification not possible" in accordance with the GHS Classification Guidance for the Japanese Government.

[Evidence Data]
(1) In classification results by domestic and international organizations, it was classified as A4 by ACGIH (ACGIH (7th, 2018)), and as E by EPA (EPA Annual Cancer Report (2018): classified in 2000).
7 Reproductive toxicity *
-
-
- - [Rationale for the Classification]
There are data on this substance in (1)-(3) and data on paraquat in (4). No obvious reproductive toxicity was observed. Therefore, it was classified as "Not classified."

[Evidence Data]
(1) In a three-generation reproductive study by feeding diets containing this substance to rats, retarded ossification, reductions in body weights and retarded opening of the vagina, etc. were noted in pups at doses showing parental animal toxicity (lung lesions) (JMPR (2003)).
(2) In a developmental toxicity test by oral gavage of this substance to female rats on Days 6-15 of gestation, reduced fetal weights and retarded ossification were noted at doses showing maternal toxicity (JMPR (2003)).
(3) In a developmental toxicity test by oral gavage of this substance to female mice on Days 6-15 of gestation, neither maternal toxicity nor fetotoxicity was seen (JMPR (2003)).
(4) In a two-generation reproductive toxicity study by feeding diets containing paraquat (CAS RN 4685-14-7) to mice, deaths and lung lesions (extensive fibrosis) were noted in both parental animals and pups (JMPR (2003)).

[Reference Data, etc.]
Data of lower purity substance
(5) In a three-generation study on this substance (paraquat ions: 32.7%) with rats, lung lesions (perivascular inflammatory cell infiltration in the lung) were seen in pups at the dose showing death and lung lesions (alveolar fibrosis, epithelialization, perivascular edema and inflammatory cell infiltration, etc.) in parental animals (JMPR (2003)).
(6) In a developmental toxicity test by oral gavage of this substance (paraquat ions: 38.2%) to female rats on Days 7-16 of gestation, no effects on fetuses were noted at the dose showing maternal toxicity (reduction in body weights) (JMPR (2003)).
(7) In a developmental toxicity test by oral gavage of this substance (paraquat ions: 38.2%)* to female mice on Days 6-15 of gestation, retarded ossification was seen at the dose showing maternal toxicity (death (5/26 mice: 4 animals killed in extremis, and one animal found dead) (JMPR (2003)). *: JMPR (2003) described that the purity was 38.2%.
(8) In a three-generation study by feeding diets containing paraquat ions: 25.8%) to rats, no parental animal toxicity was observed, but hydropic changes in the renal tubules were found in weanlings (JMPR (2003)).
8 Specific target organ toxicity - Single exposure Category 1 (lung, liver, kidney)


Danger
H370 P308+P311
P260
P264
P270
P321
P405
P501
[Rationale for the Classification]
Based on (1)-(4), it was classified in Category 1 (lung, liver, kidney).

[Evidence Data]
(1) Numerous cases of poisonings with paraquat (CAS RN 4685-14-7) by oral ingestion due to accidents or suicides are reported. As symptoms, acute pulmonary edema, pulmonary fibrosis, acute renal failure (oliguria, proteinuria, etc.) and acute liver failure (jaundice, liver hypertrophy, abnormal liver function test values) occurred (ACGIH (7th, 2018), IPCS, PIM 399 (2000), JMPR (2003), EHC 39 (1984)).
(2) Through the dermal route, multiple human cases with respiratory insufficiency and renal failure due to exposure to paraquat by accidents or suicides are reported (ACGIH (7th, 2018), JMPR (2003)). In one of them, interstitial pneumonia, intra-alveolar hemorrhage, renal tubular cell degeneration and cholestasis were noted at autopsy (JMPR (2003)).
(3) After a single dose at 110 mg/kg (converted value equivalent to this substance: 131 mg/kg, corresponding to Category 1) of paraquat to rats, diarrhea, wheezing and irregular respiration were seen as early clinical signs, and reduced body weight, pulmonary edema, congestion and hemorrhage were noted after 5-6 days. Besides, in the other report, pulmonary fibrosis occurred by 10 days after a dose (ACGIH (7th, 2018)).
(4) In ACGIH (7th, 2001), it is described that the toxicity of paraquat depends solely on its cationic moiety, all salts having equivalent toxicity.
9 Specific target organ toxicity - Repeated exposure Category 1 (lung)


Danger
H372 P260
P264
P270
P314
P501
[Rationale for the Classification]
The effects on the lung were observed within the range of Category 2 after oral administration to experimental animals in (1)-(3) and within the range of Category 1 by inhalation exposure in (4), therefore, it was classified in Category 1 (lung). The classification result was changed from the previous classification by adding new information sources and reviewing.

[Evidence Data]
(1) As a result of a study by feeding diets containing this substance at 300-700 ppm (converted guidance value: 15-35 mg/kg/day, within the range of Category 2) to rats for 90 days, intra-alveolar hemorrhage, diffuse fibrosis and proliferation of the epithelium were noted (ACGIH (7th, 2018)).
(2) As a result of a study by feeding diets containing this substance at 10-300 ppm to rats for 13 weeks, alveolar epithelial hypertrophy was seen at 300 ppm (14.2 mg paraquat ions/kg/day (a converted value equivalent to this substance: 19.6 mg/kg/day, within the range of Category 2)) (JMPR (2003), ACGIH (7th, 2018)).
(3) As a result of a study by feeding diets containing this substance at 10-300 ppm to mice for 13 weeks, deaths from pulmonary damage in two females and pulmonary edema, etc. in both sexes were seen at 300 ppm (male: 36 mg/kg/day, female: 42 mg/kg/day, within the range of Category 2) (JMPR (2003), ACGIH (7th, 2018)).
(4) In a 3-week inhalation study by exposure to respirable paraquat aerosol of this substance (6 hours/day, 5 days/week) with rats, pulmonary irritation was noted at 0.4 mg/m3 (converted guidance value: 0.00012 mg/L, within the range of Category 1) (ACGIH (7th, 2018)).
10 Aspiration hazard *
-
-
- - [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 ErC50 = 0.24 mg/L for algae (Pseudokirchneriella subcapitata) (Document for registration standards for agricultural chemicals set by the Minister of Environment to prevent harm to animals and plants in areas of public waters, 2016).
11 Hazardous to the aquatic environment Long term (Chronic) Category 1


Warning
H410 P273
P391
P501
If chronic toxicity data are used, then it is classified in Category 1 due to being not rapidly degradable (not readily degradable, a degradation rate by BOD: 0% (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, 1985)), and 96-hour NOECr = 0.02 mg/L for algae (Pseudokirchneriella subcapitata) (Document for registration standards for agricultural chemicals set by the Minister of Environment to prevent harm to animals and plants in areas of public waters, 2016).
If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained, then it is classified in Category 2 due to being not rapidly degradable (not readily degradable, a degradation rate by BOD: 0% (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, 1985)), 48-hour EC50 = 1.2 mg/L for crustacea (Daphnia magna), and 96-hour LC50 = 13 mg/L for fish (Lepomis macrochirus) (both, U.S. EPA: RED, 1997).
By drawing a comparison between the above results, it was classified in Category 1.
12 Hazardous to the ozone layer Classification not possible
-
-
- - Classification not possible due to lack of data.


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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