GHS Classification Result

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GENERAL INFORMATION
Item Information
CAS RN 121-69-7
Chemical Name N,N-Dimethylaniline
Substance ID H29-B-010
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
-
-
- - Liquid (GHS definition)
3 Aerosols Not applicable
-
-
- - Not aerosol products.
4 Oxidizing gases Not applicable
-
-
- - Liquid (GHS definition)
5 Gases under pressure Not applicable
-
-
- - Liquid (GHS definition)
6 Flammable liquids Category 4
-
Warning
H227 P370+P378
P403+P235
P210
P280
P501
Based on a flash point of 62.8 deg C (closed-cup) (ACGIH (7th, 2001)), it was classified in Category 4.
7 Flammable solids Not applicable
-
-
- - Liquid (GHS definition)
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 classified
-
-
- - It is estimated that it does not ignite at normal temperatures from an autoignition temperature of 371 deg C (ICSC (J) (1998)).
10 Pyrophoric solids Not applicable
-
-
- - Liquid (GHS definition)
11 Self-heating substances and mixtures Classification not possible
-
-
- - Test methods applicable to liquid substances are not available.
12 Substances and mixtures which, in contact with water, emit flammable gases 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 applicable
-
-
- - Organic compounds containing no oxygen, fluorine or chlorine
14 Oxidizing solids Not applicable
-
-
- - Liquid (GHS definition)
15 Organic peroxides Not applicable
-
-
- - Organic compounds containing no bivalent -O-O- structure in the molecule
16 Corrosive to metals Classification not possible
-
-
- - No data available.

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
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.
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.
1 Acute toxicity (Inhalation: Gases) Not applicable
-
-
- - Liquid (GHS definition)
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.
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.
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).
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.
4 Respiratory sensitization Classification not possible
-
-
- - Classification not possible due to lack of data.
4 Skin sensitization Classification not possible
-
-
- - Classification not possible due to lack of data.
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)).
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.
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.
8 Specific target organ toxicity - Single exposure Category 1 (central nervous system, haemal 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).
9 Specific target organ toxicity - Repeated exposure Category 1 (haemal 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.
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).

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 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.
11 Hazardous to the aquatic environment (Long-term) 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.
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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