GHS Classification Result
GENERAL INFORMATION
REFERENCE INFORMATION
PHYSICAL HAZARDS
HEALTH HAZARDS
ENVIRONMENTAL HAZARDS
NOTE:
GENERAL INFORMATION
| Item | Information |
|---|---|
| CAS RN | 101-80-4 |
| Chemical Name | 4,4'-Diaminodiphenyl ether |
| Substance ID | H29-B-009 |
| 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 |
| 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 (GESTIS (Access on June 2017)), 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 | Not classified |
- |
- | - | It is estimated that it does not ignite at normal temperatures from an autoignition temperature of 490 deg C (HSDB (Access on May 2017)). |
| 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 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 |
- |
- | - | Solid (GHS definition). |
| 14 | Oxidizing solids | Not applicable |
- |
- | - | The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is chemically bonded only to carbon or hydrogen. |
| 15 | Organic peroxides | 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. |
| 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 a report of an LD50 value of 725 mg/kg (DFGOT Vol. 6 (1994), HSDB (Access on May 2017)) for rats, it was classified in Category 4. |
| 1 | Acute toxicity (Dermal) | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| 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. |
| 2 | Skin corrosion/irritation | Classification not possible |
- |
- | - | Classification not possible due to lack of data. In the previous classification, based on a description of no irritation from a test with rats (DFGOT Vol. 6 (1994)), it was classified as "Not classified." However, since the experimental conditions such as the number of animals and dosage are unknown, it was classified as "Classification not possible." |
| 3 | Serious eye damage/eye irritation | Classification not possible |
- |
- | - | Classification not possible due to lack of data. In the previous classification, based on a description of no irritation from a test with rabbits (DFGOT Vol. 6 (1994)), it was classified as "Not classified." However, since the experimental conditions such as the number of animals and dosage are unknown, it was classified as "Classification not possible." |
| 4 | Respiratory sensitization | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| 4 | Skin sensitization | Category 1 |
Warning |
H317 |
P302+P352
P333+P313 P362+P364 P261 P272 P280 P321 P501 |
Based on a report that positive reaction was observed in 6 out of 10 animals in a test with guinea pigs (DFGOT Vol. 6 (1994)), it was classified in Category 1. |
| 5 | Germ cell mutagenicity | Category 2 |
 Warning |
H341 |
P308+P313
P201 P202 P280 P405 P501 |
As for in vivo, a micronucleus test and a chromosomal aberration test with mouse bone marrow cells, a DNA breakage test and an unscheduled DNA synthesis test with rat hepatocytes were positive, a sister chromatid exchange test with mouse bone marrow cells was negative (DFGOT Vol. 6 (1993), NTP DB (Access on May 2017)). As for in vitro, bacterial reverse mutation tests, and a mouse lymphoma test, a chromosomal aberration test and a sister chromatid exchange test with mammalian cultured cells were all positive (DFGOT Vol. 6 (1993), IARC 29 (1982), PATTY (6th, 2012), NTP TR205 (1980), NTP DB (Access on May 2017)). From the above, it was classified in Category 2 according to the GHS Classification Guidance for the Japanese Government. |
| 6 | Carcinogenicity | Category 1B |
Danger |
H350 |
P308+P313
P201 P202 P280 P405 P501 |
In carcinogenicity tests with rats and mice dosed by feeding for two years, in the rats, hepatocellular carcinomas or neoplastic nodules of the liver, and adenomas or carcinomas of the thyroid epithelial cells were observed in both sexes. In the mice, adenomas in the harderian glands and hepatocellular adenomas or carcinomas in both sexes, and adenomas of the thyroid epithelial cells in females were observed (NTP TR205 (1980), IARC 29 (1982), NTP RoC (14th, 2016)). In addition, benign or malignant tumors of the hepatocytes were also observed in the test with rats subcutaneously dosed (IARC 29 (1982), NTP RoC (14th, 2016)). As for classifications by other organizations, IARC classified it in Group 2B (IARC Suppl. 7 (1987)), NTP as R (NTP RoC (14th, 2016)), Japan Society For Occupational Health (JSOH) in Group 2B (Recommendation of Occupational Exposure Limits (2016) (proposal in 1991)), and EU in Carc. 1B (ECHA CL Inventory (Access on May 2017)). From the above, according to the classification result of IARC and JSOH, it corresponds to Category 2, but clear evidence of carcinogenicity was observed in experimental animals of two species. Therefore, it was classified in Category 2. |
| 7 | Reproductive toxicity | Category 2 |
Warning |
H361 |
P308+P313
P201 P202 P280 P405 P501 |
In a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD TG 422) with rats dosed by gavage, a decrease in the number of offspring born, a decrease in the survival rate, and jaundice were observed in the pups at 30 mg/kg/day where 4/12 maternal animals died due to delivery impairment (judged from the fact that the fetuses in the uterus had developed as a result of necropsy) (Safety Test (Ministry of Economy, Trade and Industry (METI)) (2007)). From the above, although effects on the next generation were observed in this test, general toxicity effects (effects on the liver, spleen and thyroid) were observed at 30 mg/kg/day in parental animals, therefore, it was classified in Category 2 for this hazard class. Besides, EU also classified this substance in Repr. 2 (ECHA CL Inventory (Access on May 2017)). |
| 8 | Specific target organ toxicity - Single exposure | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| 9 | Specific target organ toxicity - Repeated exposure | Category 1 (haemal system), Category 2 (pituitary, thyroid, liver, kidney, genetic organs (men)) |
Danger Warning |
H372
H373 |
P260
P264 P270 P314 P501 |
No information on humans is available. As for experimental animals, in a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test by gavage administration, decreased erythrocyte counts, an increased ratio of the reticulocytes, increased total bilirubin, and increased hemosiderin deposition in the spleen at or above 10 mg/kg/day (converted guidance value: 4.7 mg/kg/day) within the guidance value range for Category 1, and increases in ALT, AST and alkaline phosphatase activity, follicular hyperplasia of the thyroid, centrilobular hypertrophy of hepatocytes, granulation in the liver, increased extramedullary hematopoiesis in the spleen, etc. at 30 mg/kg/day (converted guidance value: 14 mg/kg/day) within the guidance value range for Category 2 were reported (Safety Test (Ministry of Economy, Trade and Industry (METI)) (2007)). In addition, in 90-day toxicity tests with rats and mice dosed by feeding, in the rats, increased mortality, alopecia, labored respiration, cyanosis, diffuse cell hyperplasia of the thyroid, pituitary hyperplasia, renal microlithiasis, testicular degeneration, atrophy of the prostate and seminal vesicle, etc. at or above 0.06% (converted guidance value: 30 mg/kg/day) within the guidance value range for Category 2 were reported. Also, in the mice, hypertrophy and hyperplasia of the thyroid at or above 0.06% (converted guidance value: 90 mg/kg/day) within the guidance value range for Category 2, testicular degeneration at or above 0.1% (converted guidance value: 150 mg/kg/day) exceeding the guidance value range for Category 2, and hypertrophy and hyperplasia of the pituitary at 0.2% (converted guidance value: 300 mg/kg/day) were reported. Moreover, in carcinogenicity tests with rats and mice dosed by feeding for two years, in the rats, hyperplasia of the thyroid follicular cells at or above 0.04% (converted guidance value: 20 mg/kg/day) within the guidance value range for Category 2, and focal mineralization of the kidney at 0.05% (converted guidance value: 25 mg/kg/day) were reported, and in the mice, hyperplasia of the thyroid follicular cells at 0.08% (converted guidance value: 120 mg/kg/day) exceeding the guidance value range for Category 2 was reported (NTP TR205 (1980), Environmental Risk Assessment for Chemical Substances Vol.9, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2011)). Among the above, as for the effects on the thyroid, they were judged to be related to the effects on the thyroid itself or the effects on the pituitary because no effect on the liver was observed in the same test. In addition, in the previous classification, the central nervous system was also regarded as the target organ, but the finding used as evidence was only lethargy, therefore, it was not adopted as the target organ. Therefore, it was classified in Category 1 (haemal system), Category 2 (pituitary, thyroid, liver, kidney, genetic organs (men)). Besides, the classification result was different from the previous one due to the use of new information sources. |
| 10 | Aspiration hazard | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| 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 EC50 = 0.99 mg/L for crustacea (Daphnia magna) (Results of Aquatic Toxicity Tests of Chemicals conducted by Ministry of the Environment in Japan (Ministry of the Environment, 2017), Environmental Risk Assessment for Chemical Substances vol. 15 (Ministry of the Environment, 2017)), it was classified in Category 1. |
| 11 | Hazardous to the aquatic environment (Long-term) | Category 1 |
Warning |
H410 |
P273
P391 P501 |
If chronic toxicity data are used, then it is classified as "Not classified" due to being not rapidly degradable (a degradation rate: 7.6% OECDTG 301 (Environmental Risk Assessment for Chemical Substances vol. 15 (Ministry of the Environment, 2017))), 72-hour NOEC (growth rate) <3.75 mg/L for algae (Pseudokirchneriella subcapitata) (Environmental Risk Assessment for Chemical Substances vol. 15 (Ministry of the Environment, 2017)). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained, then it is classified in Category 1 due to being not rapidly degradable (a degradation rate: 7.6% OECDTG 301 (Environmental Risk Assessment for Chemical Substances vol. 15 (Ministry of the Environment, 2017))), and 48-hour EC50 = 0.99 mg/L for crustacea (Daphnia magna) (Results of Aquatic Toxicity Tests of Chemicals conducted by Ministry of the Environment in Japan (Ministry of the Environment, 2017), Environmental Risk Assessment for Chemical Substances vol. 15 (Ministry of the Environment, 2017)). From the above results, it was classified in Category 1. |
| 12 | Hazardous to the ozone layer | Classification not possible |
- |
- | - | No data available. |
NOTE:
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* 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. |