GHS Classification Results by the Japanese Government

Japanese



GENERAL INFORMATION
Item Information
CAS RN 59669-26-0
Chemical Name 3,7,9,13-Tetramethyl-5,11-dioxa-2,8,14-trithia-4,7,9,12-tetraazapentadeca-3,12-diene-6,10-dione (synonym: Thiodicarb)
Substance ID R03-B-025-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 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..
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.
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 Not classified
-
-
- - It is estimated that it does not ignite at normal temperatures because it can be estimated that it does not decompose up to 184.7 deg C from the information that it decomposes at 184.7 deg C (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, 2015).
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 Classification not possible
-
-
- - The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is chemically bonded to the element other than carbon or hydrogen (N). 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.
16 Corrosive to metals Classification not possible
-
-
- - 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) Category 2


Danger
H300 P301+P310
P264
P270
P321
P330
P405
P501
[Rationale for the Classification]
Based on (1) to (7), it was classified in Category 2 by adopting the category with the higher hazard. Based on the new findings, the classification result was changed.

[Evidence Data]
(1) LD50 for rats (males): 46.5 mg/kg (EPA Pesticides RED (1998))
(2) LD50 for rats (females): 39.1 mg/kg (EPA Pesticides RED (1998))
(3) LD50 for rats: 50 mg/kg (EFSA (2005))
(4) LD50 for mice: 75 mg/kg (JMPR (2000))
(5) LD50 for rats: between 39 to 398 mg/kg (ACGIH (2020), HSDB in PubChem (Accessed Aug. 2021))
(6) LD50 for rats: between 50 to 100 mg/kg (JMPR (2000))
(7) LD50 for mice: between 73 to 79 mg/kg (ACGIH (2020), EPA Pesticides RED (1998), HSDB in PubChem (Accessed Aug. 2021))
1 Acute toxicity (Dermal) Not classified
-
-
- - [Rationale for the Classification]
Based on (1) to (3), it was classified as "Not classified."

[Evidence Data]
(1) LD50 for rabbits: between 2,540 mg/kg to 6,310 mg/kg (ACGIH (2020), HSDB in PubChem (Accessed Aug. 2021))
(2) LD50 for rabbits: > 2,000 mg/kg (EPA Pesticides RED (1998), HSDB in PubChem (Accessed Aug. 2021))
(3) LD50 for rats: > 2,000 mg/kg (EFSA (2005))
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) Category 2


Danger
H330 P304+P340
P403+P233
P260
P271
P284
P310
P320
P405
P501
[Rationale for the Classification]
Based on (1), it was classified in Category 2. Based on the new findings, the classification result was changed.

[Evidence Data]
(1) LC50 (4 hours) for rats: 0.52 mg/L (ACGIH (2020), PubChem (Accessed Aug. 2021))
2 Skin corrosion/irritation Not classified
-
-
- - [Rationale for the Classification]
Based on (1) to (4), it was classified as "Not classified" in accordance with the GHS Classification Guidance for the Japanese Government.

[Evidence Data]
(1) This substance was not a skin irritant substance (EFSA (2005)).
(2) This substance did not irritate the skin (JMPR (2000)).
(3) It was reported that, in a primary skin irritation test with rabbits, no skin irritation was observed (EPA Pesticides RED (1998)).
(4) It was reported that, in a skin irritation test with rabbits, no skin irritation was observed (ACGIH (7th, 2020)).
3 Serious eye damage/eye irritation Not classified
-
-
- - [Rationale for the Classification]
Based on (1) to (4), it was classified as "Not classified." Also, based on the new findings, the classification result was changed.

[Evidence Data]
(1) This substance was not an eye irritant substance (EFSA (2005)).
(2) This substance did not irritate the eye (JMPR (2000)).
(3) It was reported that, in an eye irritation test with rabbits, slight eye irritation was observed (EPA Pesticides RED (1998)).
(4) It was reported that, in an eye irritation test with rabbits, slight irritation in the eyes was observed, which was rapidly reversible (ACGIH (7th, 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]
Classification not possible due to lack of data. Besides, although the qualitative findings of (1) to (3) suggested skin sensitization, they were not used for classification because the test conditions, etc. were unknown, and the classification result was changed.

[Reference Data, etc.]
(1) In a Magnusson & Kligman test, this substance was positive for skin sensitization (EFSA (2005)).
(2) Weakly positive responses were seen in a skin sensitization study for this substance in guinea pigs, but an extensive study in humans given patch tests showed no evidence of skin sensitization (JMPR (2000)).
(3) In a skin sensitization study in guinea pigs, this substance induced a weak dermal sensitization reaction (ACGIH (7th, 2020), EPA Pesticides RED (1998), HSDB (Accessed Sep. 2021)).
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, all of 3 studies (micronucleus test, dominant lethal test, and unscheduled DNA synthesis (UDS) test) showed negative results. The purity of the test substance administered was 95.4% in the UDS test, while the purities in the other two tests were over 99% (EFSA (2005)).
(2) As for in vitro, a bacterial reverse mutation test showed negative results, a gene mutation assay using the mouse lymphoma cells showed positive or equivocal results (positive at cytotoxic concentrations), and a chromosomal aberration test using the cultured mammalian cells showed negative results (EPA Pesticides RED (1998), EFSA (2005), JMPR (2000), ACGIH (7th, 2020)).
6 Carcinogenicity Category 2


Warning
H351 P308+P313
P201
P202
P280
P405
P501
[Rationale for the Classification]
Based on (1) to (3), it was classified in Category 2. It was classified based on the new information source.

[Evidence Data]
(1) As for the classification results for carcinogenicity by domestic and international evaluation organizations, the EPA classified it in Group B (Probable Human Carcinogen) (EPA OPP Annual Cancer Report 2020 (Accessed August 2020): Classified in 1996) and the ACGIH classified it in A3 (ACGIH (7th, 2020)).
(2) In one of two carcinogenicity studies with rats dosed by feeding for two years, increased incidences of interstitial cell tumors in the testes were observed at the highest dose (60 mg/kg/day) (EPA Pesticides RED (1998), ACGIH (7th, 2020)), and in another study, increased incidences of liver tumors (neoplastic nodules, hepatocellular carcinoma) were observed at 1 to 10 mg/kg/day (ACGIH (7th, 2020)).
(3) In a 97-week feeding study among two carcinogenicity studies with mice, an increase in liver tumors (incidences of hepatocellular adenomas, hepatocellular carcinomas and combined hepatocellular adenomas and carcinomas) was observed at the highest dose (1,000 mg/kg/day). In a 2-year feeding study (1 to 10 mg/kg/day), no increased incidences of treatment-related tumors were observed (EPA Pesticides RED (1998), ACGIH (7th, 2020)).

[Reference Data, etc.]
(4) The overall conclusion of the EFSA was that this substance was not carcinogenic since the occurrence of liver tumors in mice was of no relevance to human risk assessment because the dose at which the tumors occurred exceeded the maximum tolerated dose (EFSA (2005)). In the latest evaluation of the ACGIH, this substance was classified in A3 because it produced liver and testicular tumors following lifetime feeding to rats and liver tumors in mice (ACGIH (7th, 2020)).
7 Reproductive toxicity Category 2


Warning
H361 P308+P313
P201
P202
P280
P405
P501
[Rationale for the Classification]
Based on (1) to (3), it was classified in Category 2.

[Evidence Data]
(1) It was reported that, in a two-generation reproduction toxicity study with rats dosed by feeding, reduced body weight gain and decreased food consumption in parental animals and decreased body weights and viability in offspring were observed at or above 15 mg/kg/day (EPA Pesticides RED (1998), ACGIH (7th, 2020)).
(2) It was reported that, in two developmental toxicity studies with rats dosed by gavage (days 6 to 19 of gestation or days 6 to 15 of gestation), at the highest dose (10 to 30 mg/kg/day), reduced body weight gain and symptoms (tremor, salivation, lethargy, etc.) were observed in parental animals in both studies, and in offspring, slight developmental effects (lower fetal body weight, skeletal variations, and delayed ossification) were observed in one study, and no developmental effects were observed in the other test (EPA Pesticides RED (1998), ACGIH (7th, 2020)).
(3) It was reported that, in a developmental toxicity study (days 6 to 19 of gestation (rabbits), days 6 to 16 of gestation (mice)) with rabbits and mice dosed by gavage, no developmental toxicity was observed (EPA Pesticides RED (1998), ACGIH (7th, 2020)).
8 Specific target organ toxicity - Single exposure Category 1 (nervous system)


Danger
H370 P308+P311
P260
P264
P270
P321
P405
P501
[Rationale for the Classification]
Based on (1) and (2), effects on the nervous system were observed in animal tests, and therefore, it was classified in Category 1 (nervous system).

[Evidence Data]
(1) It was reported that, in an acute oral toxicity test with rats (acute neurotoxicity test), signs of cholinergic effects (miosis, decreased body temperature) and marked depression of brain acetylcholinesterase activity were observed at 5 mg/kg (within the range for Category 1), and effects in an FOB observation, and marked depression of ChE activity in plasma, erythrocytes, and brain were observed at 20 mg/kg and 40 mg/kg (within the range for Category 1) (JMPR (2000)).
(2) It was reported that, in an acute oral toxicity test with rats, tremors and increased salivation were observed. Also, the LD50 was reported to be between 39 mg/kg to 398 mg/kg (ACGIH (2020)).
9 Specific target organ toxicity - Repeated exposure Category 1 (nervous system, blood system, liver)


Danger
H372 P260
P264
P270
P314
P501
[Rationale for the Classification]
In (1) to (5), effects on the nervous system and blood system were observed at doses within the range for Category 1 and Category 2, and in (6) to (8), effects on the liver were observed at doses mainly within the range for Category 1. Based on the above, it was classified in Category 1 (nervous system, blood system, liver). Besides, since the extent of the effects on the kidney observed in (6) was unknown and no effects were observed in a longer-term test in (8), the kidney was not adopted as target organ. Based on the new findings, the classification result was changed.

[Evidence Data]
(1) It was reported that, in a 4-week oral toxicity study with rats dosed by feeding, reduced plasma and erythrocyte cholinesterase (ChE) activities were observed at 30 mg/kg/day (within the range for Category 2) (EPA Pesticides RED (1998), ACGIH (7th, 2020)).
(2) It was reported that, in a 13-week oral toxicity study with rats dosed by feeding, decreased body weight gain, decreased red blood cell cholinesterase (ChE), and decreased hemoglobin were observed at 10 mg/kg/day (within the range for Category 1) (EPA Pesticides RED (1998), ACGIH (7th, 2020)).
(3) It was reported that, in a 13-week oral toxicity study with dogs dosed by feeding, decreased red blood count, hemoglobin, and hematocrit were observed at 45 mg/kg/day (within the range for Category 2) (EPA Pesticides RED (1998), ACGIH (7th, 2020)).
(4) It was reported that, in a one-year chronic toxicity study with dogs dosed by feeding, inhibition of ChE was observed at 12.8 mg/kg/day (males) and 13.8 mg/kg/day (females) (within the range for Category 2), and decreased erythrocytes, hemoglobin, and hematocrit were observed at 38.3 mg/kg/day (males) and 39.5 mg/kg/day (females) (within the range for Category 2) (EPA Pesticides RED (1998), ACGIH (7th, 2020)).
(5) It was reported that, in a 2-year combined chronic toxicity/carcinogenicity study with rats dosed by feeding, increased incidence of extramedullary hematopoiesis (males), increased incidence of testicular interstitial cell tumors (males), and decreased red blood cell ChE (females) were observed at 12 mg/kg/day (within the range for Category 2) (EPA Pesticides RED (1998), ACGIH (7th, 2020)).
(6) It was reported that, in a 30-day oral toxicity test with rats, effects on the liver (diffuse vacuolation), kidney (tubular cell damage) and spleen (increased red pulp deposits) were observed at 10 mg/kg/day (converted guidance value: 3.33 mg/kg/day, within the range for Category 1) (ACGIH (7th, 2020)).
(7) It was reported that, in a 6-month oral toxicity study with dogs dosed by feeding, increased liver weight and an increase in serum GPT (ALT) were observed at 45 mg/kg/day (within the range for Category 2) (EPA Pesticides RED (1998), ACGIH (7th, 2020)).
(8) It was reported that, in a 2-year combined chronic toxicity/carcinogenicity study with rats dosed by feeding, hepatocyte hypertrophy, neoplastic nodules, and carcinomas of the liver were observed at 1 mg/kg/day (within the range for Category 1) (ACGIH (7th, 2020)).

[Reference Data, etc.]
(9) It was reported that, in a 21-day dermal toxicity study with rabbits (6 hours/day, 5 days/week), macrocytic anemia, erythema, and edema were observed at 2,000 mg/kg/day (converted guidance value: 333 mg/kg/day, in the range corresponding to "Not classified") (EPA Pesticides RED (1998), ACGIH (7th, 2020)).
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 = 0.027 mg/L for crustacea (Daphnia magna) (EPA Pesticides RED, 1998, OPP Pesticide Ecotoxicity Database, 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, 2015).
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 (BIOWIN) and 21-day NOEC = 0.009 mg/L for crustacea (Daphnia magna) (EPA Pesticides RED, 1998, OPP Pesticide Ecotoxicity Database).
If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained (fish), then it is classified in Category 1 due to being not rapidly degradable and 96-hour LC50 = 0.53 mg/L for fish (Cyprinodon variegatus) (EPA Pesticides RED, 1998, OPP Pesticide Ecotoxicity Database).
From the above results, it was classified in Category 1.
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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