Latest GHS Classification Results by the Japanese Government (edited by NITE)
GENERAL INFORMATION
REFERENCE INFORMATION
PHYSICAL HAZARDS
HEALTH HAZARDS
ENVIRONMENTAL HAZARDS
NOTE:
GENERAL INFORMATION
| Item | Information |
|---|---|
| CAS RN | 121-69-7 |
| Chemical Name | N,N-Dimethylaniline |
| Substance ID | m-nite-121-69-7_v1 |
| Download of Excel format | Excel file |
REFERENCE INFORMATION
| Item | Information |
|---|---|
| Guidance used for the classification (External link) | To Guidance List |
| UN GHS document (External link) | To UN GHS document |
| FAQ（GHS classification results by the Japanese Government） | To FAQ |
| List of Information Sources (Excel file) | List of Information Sources |
| List of Definitions/Abbreviations | Definitions/Abbreviations |
| Sample Label by MHLW (External link) | To Workplace Safety Site (MHLW) |
| Sample SDS by MHLW (External link) | To Workplace Safety Site (MHLW) |
| OECD/eChemPortal (External link) | To OECD/eChemPortal (External link) |
| Hazard class | Classification | Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | Classification year (FY) | GHS Classification Guidance for the Japanese Government | |
|---|---|---|---|---|---|---|---|---|
| 1 | Explosives | Not classified (Not applicable) |
- |
- | - | There are no chemical groups associated with explosive properties present in the molecule. | FY2017 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 2 | Flammable gases | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) | FY2017 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 3 | Aerosols | Not classified (Not applicable) |
- |
- | - | Not aerosol products. | FY2017 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 4 | Oxidizing gases | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) | FY2017 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 5 | Gases under pressure | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) | FY2017 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 6 | Flammable liquids | Category 4 |
Warning |
H227 | P370+P378 P210 P280 P403 P501 |
Based on a flash point of 62.8 deg C (closed-cup) (ACGIH (7th, 2001)), it was classified in Category 4. | FY2017 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 7 | Flammable solids | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) | FY2017 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 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. | FY2017 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 9 | Pyrophoric liquids | Not classified |
- |
- | - | It is estimated that it does not ignite at normal temperatures from an autoignition temperature of 371 deg C (ICSC (J) (1998)). | FY2017 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 10 | Pyrophoric solids | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) | FY2017 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 11 | Self-heating substances and mixtures | Classification not possible |
- |
- | - | Test methods applicable to liquid substances are not available. | FY2017 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 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). | FY2017 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 13 | Oxidizing liquids | Not classified (Not applicable) |
- |
- | - | Organic compounds containing no oxygen, fluorine or chlorine | FY2017 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 14 | Oxidizing solids | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) | FY2017 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 15 | Organic peroxides | Not classified (Not applicable) |
- |
- | - | Organic compounds containing no bivalent -O-O- structure in the molecule | FY2017 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 16 | Corrosive to metals | Classification not possible |
- |
- | - | No data available. | FY2017 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 17 | Desensitized explosives | - |
- |
- | - | - | - | - |
| Hazard class | Classification | Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | Classification year (FY) | GHS Classification Guidance for the Japanese Government | |
|---|---|---|---|---|---|---|---|---|
| 1 | Acute toxicity (Oral) | Category 4 |
 Warning |
H302 | P301+P312 P264 P270 P330 P501 |
Based on the reports that LD50 values for rats were 1,300 mg/kg (ACGIH (7th, 2001), DFGOT Vol. 3 (1992)), 1,348 mg/kg (DFGOT Vol. 3 (1992)), and 1,410 mg/kg (ACGIH (7th, 2001), PATTY (6th, 2012)), it was classified in Category 4. | FY2017 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 1 | Acute toxicity (Dermal) | Category 4 |
Warning |
H312 | P302+P352 P362+P364 P280 P312 P321 P501 |
Based on two reports that LD50 values for rabbits were 1,692 mg/kg (DFGOT vol. 3 (1992)) and 1,770 mg/kg (ACGIH (7th, 2001)), it was classified in Category 4. | FY2017 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 1 | Acute toxicity (Inhalation: Gases) | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) | FY2017 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 1 | Acute toxicity (Inhalation: Vapours) | Category 2 |
 Danger |
H330 | P304+P340 P403+P233 P260 P271 P284 P310 P320 P405 P501 |
Though there is no report on an LC50 value, there is a report that in a single inhalation exposure test with rats, 40% of them died within 4 days after inhalation exposure for 4 hours at 380 ppm (DFGOT Vol. 3 (1992)), and the LC50 value is considered to be within the range of 100-500 ppm. Therefore, it was classified in Category 2. Besides, since the exposure concentration is lower than 90% of the saturated vapor pressure concentration (924 ppm), a reference value in the unit of ppm was applied as vapour with little mist. By reviewing the data, the classification result was revised from the previous classification. | FY2017 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 1 | Acute toxicity (Inhalation: Dusts and mists) | Classification not possible |
- |
- | - | Classification not possible due to lack of data. Because in the information of DFGOT Vol. 3 (1992) which was adopted as the evidence in the previous classification, the exposure concentration (380 ppm) is lower than 90% of the saturated vapor pressure concentration (924 ppm), it is thought that it existed as vapour with little mist. Therefore, the classification result was revised. | FY2017 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 2 | Skin corrosion/irritation | Not classified |
- |
- | - | It is reported that no irritation was found in a human patch test (HSDB (Access on May 2017)), and mild irritation was reported in an irritation test with rabbits (BUA 91 (1992)). Therefore, it was classified "Not classified" (Category 3 in UN GHS classification). |
FY2017 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 3 | Serious eye damage/eye irritation | Category 2A |
Warning |
H319 | P305+P351+P338 P337+P313 P264 P280 |
It is reported that it causes irritation or burns to human eyes (HSDB (Access on May 2017)), and there is a report that it was moderately irritating in an application test with rabbit eyes (HSDB (Access on May 2017)). Therefore, it was classified in Category 2. | FY2017 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 4 | Respiratory sensitization | Classification not possible |
- |
- | - | Classification not possible due to lack of data. | FY2017 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 4 | Skin sensitization | Classification not possible |
- |
- | - | Classification not possible due to lack of data. | FY2017 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 5 | Germ cell mutagenicity | Classification not possible |
- |
- | - | Classification not possible due to lack of data. There is no in vivo data. As for in vitro, it was negative in bacterial reverse mutation tests, and positive in all of a mouse lymphoma test, a micronucleus test, a chromosomal aberration test, and a sister chromatid exchange test with mammalian cultured cells (DFGOT Vol. 21 (2005), DFGOT Vol. 3 (1992), ACGIH (7th, 2001), IARC 57 (1993), NTP DB (Access on May 2017), NTP TR360 (1989), OEL Documentations (Japan Society For Occupational Health (JSOH), 1993)). | FY2017 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 6 | Carcinogenicity | Category 2 |
 Warning |
H351 | P308+P313 P201 P202 P280 P405 P501 |
In a 2-year carcinogenicity study with rats and mice dosed by gavage, in rats, spleen sarcoma in 3/50 animals and osteosarcoma in 1/50 animals were found in the high dose group of males. The incidence of splenic sarcoma was higher than spontaneous incidence and was considered to be the effects due to the administration of this substance. On the other hand, in mice, a slight increase in the incidence of the forestomach papillomas was observed in females of the high dose group (NTP TR360 (1989)). It was concluded in NTP that spleen sarcoma in male rats and forestomach papilloma in female mice were some evidence of carcinogenicity and equivocal evidence of carcinogenicity, respectively (NTP TR 360 (1989)). However, IARC concluded that evidence of carcinogenicity in laboratory animals was limited and classified it in Group 3 (IARC 57 (1993)). In addition, EU classified it in Carc. 2 (ECHA CL Inventory (Access on May 2017)) while ACGIH classified it in A4 (ACGIH (7th, 2001)). Aniline (CAS RN 62-53-3: aniline is produced as a secondary metabolite in the in vitro experiment in which this substance was cultured with liver microsome), which is the basic structure of this substance, induced splenic tumor, and it was classified in Category 2 (classification results in fiscal year 2016 and 2009). Based on this, it was classified in Category 2. | FY2017 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 7 | Reproductive toxicity | Classification not possible |
- |
- | - | In a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test with rats dosed by gavage (OECD TG 422), reproductive and developmental effects were not observed at up to 100 mg/kg day where general toxicity effects (effects on the haemal system, etc.) were seen (Safety Test (Ministry of Economy, Trade and Industry (METI, 2011))). In addition, as a result of administration by gavage at 365 mg/kg/day during the organogenesis period to pregnant mice (gestational day 6-13), 6% of dams died, but no abnormalities were seen in pups by postnatal day 3 (IARC 57 (1993), Environmental Risk Assessment for Chemical Substances Vol. 7, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2009)). From the above, the combined repeated dose toxicity study with the reproduction/developmental toxicity screening test is a screening test, and it cannot be classified as "Not classified" only with this result. In addition, the developmental toxicity test with pregnant mice is a test with only one dose and is considered to be an insufficient test to conclude that there is no developmental effect. Therefore, it was classified as "Classification not possible" for this hazard class. | FY2017 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 8 | Specific target organ toxicity - Single exposure | Category 1 (central nervous system, blood system), Category 3 (narcotic effects) |
Danger Warning |
H370 H336 |
P308+P311 P260 P264 P270 P321 P405 P501 P304+P340 P403+P233 P261 P271 P312 |
There is a description that clinical signs of intoxication with this substance in humans were headaches, cyanosis, dizziness, labored breathing, paralysis and convulsions (HSDB (Access on May 2017)). As cases of accidental exposure, there are reports that a worker who was exposed to high-temperature vapors from a tub containing a mixture of this substance and phenol for several minutes, collapsed immediately after that, was unconscious for 8 hours, and complained of visual disturbances, noise in the ears, and intense abdominal pain, and that a worker developed poisoning symptoms after 7 hours of baling this substance from one container to another (ACGIH (7th, 2001), Environmental Risk Assessment for Chemical Substances Vol.7, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2009)). It was stated that the symptoms of these two cases were closely similar to those of aniline poisoning (ACGIH (7th, 2001), Environmental Risk Assessment for Chemical Substances Vol. 7, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2009)). As for experimental animals, there are reports that methemoglobin production was seen in a single oral administration of 50 mg/kg of this substance to dogs (ACGIH (7th, 2001), DFGOT Vol. 3 (1992), BUA 91 (1992)), and in a single oral administration of 48 mg/kg of this substance to cats (BUA 91 (1992)), and that symptoms of intoxication in cats were cyanosis, dyspnea and ataxia (BUA 91 (1992)). The doses in these tests are within the guidance value range for Category 1. In addition, there is a report that in a single oral administration test with guinea pigs, at 2000 mg/kg corresponding to Category 2, they showed weakness, tremors, tonic and clonic convulsions, and slowing of respiration, followed by death (HSDB (Access on May 2017)). Together with the above information, the target organs of this substance were considered to be the central nervous system and haemal system. There is also the possibility of having narcotic effects because it acts on the central nervous system. Therefore, it was classified in Category 1 (central nervous system, haemal system), Category 3 (narcotic effects). |
FY2017 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 9 | Specific target organ toxicity - Repeated exposure | Category 1 (blood system) |
Danger |
H372 | P260 P264 P270 P314 P501 |
As for humans, it was reported that a methemoglobin level reached 5.2% in some of the workers engaged in production of this substance for a long time (the number of exposed persons and the exposure concentration not specified), whereas methemoglobin was observed in only one person of the control group (18 persons) whose methemoglobin level was 2%. Also, it was reported that anemia (reduction of the erythrocyte count and hemoglobin level), and an increase in reticulocytes were observed (DFGOT Vol. 3 (1992), OEL Documentations (Japan Society For Occupational Health (JSOH, 1993))). As for experimental animals, it was reported that in a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test with rats dosed by gavage (OECD TG 422), at or above 1mg/kg/day (converted guidance value: 0.47 mg/kg/day) within the guidance value range for Category 1, hyperplasia of erythroblasts in the bone marrow and congestion of the spleen, and at or above 10 mg/kg/day (converted guidance value: 4.7 mg/kg/day), increased extramedullary hematopoiesis in the spleen, and 100 mg/kg/day (converted guidance value: 47 mg/kg/day) within the guidance value range for Category 2, lower values of erythrocyte count, hemoglobin concentration, hematocrit value, mean corpuscular hemoglobin concentration and increased extramedullary hematopoiesis in the liver, atrophy of the white pulp of the spleen, hyperplasia of the erythroblastoid cells in the bone marrow, etc. were observed (Safety Test (Ministry of Economy, Trade and Industry (METI, 2011))). Other than this, 13-week repeated dose toxicity tests with rats and mice dosed by gavage and a 2-year carcinogenicity test with rats and mice dosed by gavage were conducted, and rats were more affected than mice. In a 13-week test with rats, enlargement and increased hematopoiesis of the spleen and kidney were observed at 31.25 mg/kg/day or more (converted guidance value: 22.57 mg/kg/day), and hemosiderosis of the liver and hyperplasia of hematopoietic cells of the bone marrow were seen at or above 62.5 mg/kg/day (converted guidance value: 45.14 mg/kg/day), and a reduction in motor activity was noted at or above 125 mg/kg/day (converted guidance value: 90.28 mg/kg/day). In a two-year carcinogenicity study with rats, hemosiderosis and increased hematopoiesis of the spleen were seen at or above 3 mg/kg/day within the guidance value range for Category 1, and also fatty metamorphosis and fibrosis in the spleen were observed at 30 mg/kg/day within the guidance value range for Category 2 (NTP TR360 (1989), Environmental Risk Assessment for Chemical Substances Vol.7, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2009), DFGOT Vol. 3 (1992), ACGIH (7th, 2001)). Besides, there are reports on the inhalation test with rats where it is reported that brain and liver functions were affected in addition to the haemal system in a 100-consecutive-day exposure test, however, the Tentative Hazard Assessment Sheet (Environmental Risk Assessment for Chemical Substances Vol.7 (Ministry of the Environment, 2009)) states that the details are unknown, and also in the OEL Documentations (Japan Society For Occupational Health (JSOH), 1993), there is a description that the brain and liver are not considered to be target organs due to poor reliability of exposure technology and insufficient dose response relationship. Also, it is reported that in a 4-month exposure test with rats (6 hours/day, 6 days/week), the effect on the liver function was observed in addition to the effect on the haemal system, but the Tentative Hazard Assessment Sheet (Environmental Risk Assessment for Chemical Substances Vol.7 (Ministry of the Environment, 2009)) states that the details are unknown, and DFGOT Vol.3 (1992) states that it is an inadequately documented study. Therefore, these were not used for classification. From the above secondary or adaptive findings related to methaemoglobin production and hemolytic anemia were found in the spleen, liver, bone marrow, kidney, etc. and it was classified in Category 1 (haemal system). In the previous classification, the spleen and liver were adopted as target organs in addition to the haemal system, but the classification was revised due to the fact that the detail are unknown, and these are considered to be secondary or adaptive effects. |
FY2017 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 10 | Aspiration hazard | Classification not possible |
- |
- | - | Classification not possible due to lack of data. Besides, from the numerical data (viscosity: 1.300 mPa*s (25 deg C), density: 0.9537 g/cm3 (20 deg C)) listed in HSDB (Access on May 2017), the kinematic viscosity is calculated as 1.363 mm2/sec (25/20 deg C). | FY2017 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| Hazard class | Classification | Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | Classification year (FY) | GHS Classification Guidance for the Japanese Government | |
|---|---|---|---|---|---|---|---|---|
| 11 | Hazardous to the aquatic environment Short term (Acute) | Category 2 |
- |
H401 | P273 P501 |
From 24-hour EC50 = 5.8 mg/L for crustacea (Daphnia magna) (EPA AQUIRE:2017, Pedersen,F.,et al(1998)), it was classified in Category 2. | FY2017 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 11 | Hazardous to the aquatic environment Long term (Chronic) | Category 2 |
 - |
H411 | P273 P391 P501 |
If chronic toxicity data are used, then it is classified as "Not classified" due to being not rapidly degradable (non-biodegradable, a degradation rate by BOD: 1.9% (J-CHECK, 1976)), and 72-hour NOEC (growth rate) = 14 mg/L for algae (Chlorella pyrenoidosa) (ECETOC TR91: 2003). 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 (non-biodegradable, a degradation rate by BOD: 1.9% (J-CHECK, 1976)), and 24-hour EC50 = 5.8 mg/L for crustacea (Daphnia magna) (EPA AQUIRE: 2017). From the above results, it was classified in Category 2. |
FY2017 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 12 | Hazardous to the ozone layer | Classification not possible |
- |
- | - | No data available. | FY2017 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
NOTE:
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