GHS Classification Result
GENERAL INFORMATION
REFERENCE INFORMATION
PHYSICAL HAZARDS
HEALTH HAZARDS
ENVIRONMENTAL HAZARDS
NOTE:
GENERAL INFORMATION
| Item | Information |
|---|---|
| CAS RN | 101-68-8 |
| Chemical Name | Methylenebis(4,1-phenylene) diisocyanate [4'4-MDI] |
| Substance ID | H27-B-068/C-104B_P |
| Classification year (FY) | FY2015 |
| 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 |
| 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 |
- |
- | - | No data available. |
| 8 | Self-reactive substances and mixtures | Classification not possible |
- |
- | - | There is a chemical group associated with self-reactive properties (cyanate ester) present in the molecule, but the classification is not possible due to no data. |
| 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 240 deg C (ICSC (1999)). |
| 11 | Self-heating substances and mixtures | Classification not possible |
- |
- | - | Test methods applicable to solid 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 |
- |
- | - | 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 |
- |
- | - | It is solid with a melting point of 55 deg C or lower, but the classification is not possible due to no data. |
| Hazard class | Classification | Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | |
|---|---|---|---|---|---|---|
| 1 | Acute toxicity (Oral) | Not classified |
- |
- | - | Based on an LD50 value of 31,600 mg/kg (CICAD 27 (2000)) for rats, it was classified as "Not classified." |
| 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) | Category 2 |
 Danger |
H330 | P304+P340 P403+P233 P260 P271 P284 P310 P320 P405 P501 |
Based on reports of LC50 values (4 hours) for rats of 0.369 mg/L (male), 0.380 mg/L (female) (ACGIH (7th, 2001)), it was classified in Category 2. Besides, the reference value for dust was applied because the test substance is a solid. |
| 2 | Skin corrosion/irritation | Category 2 |
 Warning |
H315 | P302+P352 P332+P313 P362+P364 P264 P280 P321 |
There is a report that this substance was irritating to human skin (EU-RAR (2005)). In addition, there are reports that this substance was irritating to rabbit skin (EU-RAR (2005), IARC 71 (1999)), and that it was slightly irritating (EU-RAR (2005)). From the above, it was classified in Category 2. Besides, this substance was classified as "Skin. Irrit. 2 H315" in EU CLP classification (ECHA CL Inventory (Access on September 2015)). |
| 3 | Serious eye damage/eye irritation | Category 2B |
Warning |
H320 | P305+P351+P338 P337+P313 P264 |
There are reports in eye irritation tests with rabbits that slight irritation was observed (EU-RAR (2005)), and that it was not irritating (EU-RAR (2005)). From the above, it was classified in Category 2B. Besides, this substance was classified as "Eye. Irrit. 2 H319" in EU CLP classification (ECHA CL Inventory (Access on September 2015)). |
| 4 | Respiratory sensitization | Category 1 |
 Danger |
H334 | P304+P340 P342+P311 P261 P284 P501 |
There is a report that this substance causes asthma in humans (IARC 71 (1999)), and there is a description that this substance causes respiratory tract sensitization in humans and animals (ECETOC TR 77 (1999)). In addition, Japan Society For Occupational Health (JSOH) classified it in occupational sensitizers to the airway Group 1 (Recommendation of Occupational Exposure Limits (2015)), and DFG as Sah (DFGOT Vol. 14 (2000)). From the above, it was classified in Category 1. Besides, this substance was classified as "Resp. Sens. 1 H334" in EU CLP classification (ECHA CL Inventory (Access on September 2015)). |
| 4 | Skin sensitization | Category 1 |
Warning |
H317 | P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501 |
There is a report that in a maximization test with guinea pigs, as a result of an application of this substance (95%), sensitization was observed (EU-RAR (2005)). In addition, there is a report that in a patch test in humans, sensitization was shown by an application of this substance (EU-RAR (2005)). It is concluded in EU-RAR (2005) that this substance is a skin sensitizer (EU-RAR (2005)). From the above, it was classified in Category 1. Besides, this substance was classified as "Skin sens. 1 H317" in EU CLP classification (ECHA CL Inventory (Access on September 2015)). |
| 5 | Germ cell mutagenicity | Classification not possible |
- |
- | - | The substance was classified as "Classification not possible" because it was not possible to classify a substance as "Not classified" according to the revised GHS classification guidance for the Japanese government. As for in vivo, a micronucleus test with mice was negative (DFGOT Vol. 8 (1997)). As for in vitro, bacterial reverse mutation tests gave positive and negative results, a mouse lymphoma test with mammalian cultured cells was positive, a chromosomal aberration test and a sister chromatid exchange test with human cultured lymphocytes were positive and negative, and a micronucleus test with cultured human lymphocytes was negative (CICAD 27 (2000), ACGIH (7th, 2001), OEL Documentations (Japan Society For Occupational Health (JSOH), 1993), DFGOT vol. 8 (1997), IARC 71 (1999), NTP DB (Access on October 2015)). |
| 6 | Carcinogenicity | Classification not possible |
- |
- | - | As for humans, International Agency for Research on Cancer (IARC) evaluated three cohort studies and one case-control study on the carcinogenic risks associated with occupational exposures to isocyanates. As a result, neither a strong association nor consistent pattern was shown for the carcinogenic risk in any of the sites investigated, and it was concluded that there was inadequate evidence of carcinogenicity in humans for both the monomer and the polymer (PMDI) of this substance (IARC 71 (1999)). As for experimental animals, there is a description that as a result of 2-year inhalation exposure to this substance (4,4'-MDI) in rats, at the high dose (2.05 mg/m3), a bronchiolar/alveolar adenoma was found in one animal (CICAD 27 (2000), IRIS Summary (Access on August 2015)), in addition, proliferation of the alveolar epithelium considered to be a preneoplastic lesion was observed (IRIS Summary (Access on August 2015)). In addition, there is a description that as a result of 2-year inhalation exposure to the polymer of this substance (PMDI) in rats, pulmonary adenomas were observed in males (6/60) and females (2/59) at the high dose (6.03 mg/m3) (CICAD 27 (2000), IRIS Summary (Access on August 2015)). IARC used only the latter polymer data for evaluation, and it was concluded that there is limited evidence for carcinogenicity of a mixture containing this substance and the polymer of this substance in experimental animals (IARC 71 (1999)). As for classification results by other organizations, IARC, as mentioned above, classified it in Group 3 in 1999 due to insufficient evidence in humans and limited evidence in experimental animals (IARC 27 (1999)), and US EPA classified MDI and MDI polymers (PMDI) as "CBD (cannot be determined)" in 1998. On the other hand, EU conducted a risk assessment of a mixture of isomers of this substance (MDI), and it was concluded just as IARC, that the evidence for carcinogenicity in humans was insufficient, and the evidence for carcinogenicity in experimental animals was limited. Nevertheless, it is described in the section on the classification in the evaluation document that the CMR working group proposed Carc. Cat. 3 (EU-RAR (2005)). Currently it corresponds to Carc. 2 in CLP classification, but evidence for classification was unknown from available documents. From the above, it is not appropriate to adopt Category 2 because the evidence for the classification in EU is unknown. According to the GHS classification guidance for the Japanese government which was revised after the classification, based on the previous classification results by IARC and EPA, it was classified as "Classification not possible" for this hazard class. |
| 7 | Reproductive toxicity | Classification not possible |
- |
- | - | There is no information on reproductive effects in humans. As for experimental animals, in a developmental toxicity test in which pregnant rats were exposed by inhalation to this substance (4,4'-MDI) during the organogenesis period (gestational days 6-15), at the high dose group (9 mg/m3), increases in absolute and relative weight of the lung in maternal animals, and a slight increase in asymmetric sternebrae in fetuses were observed (CICAD 27 (2000), IRIS Tox Review (1998), EU-RAR (2005)). From the result of this test, because merely a skeletal variation was observed in the fetuses at the dose where adverse effects were observed in the maternal animals, it is not appropriate to classify in Category due to minor developmental effects. Other than this, there is no test result for evaluating the effects on sexual function and fertility and developmental effects of this substance. Therefore, classification was not possible due to lack of data for this hazard class. Besides, for the polymer of isomeric mixture of this substance (PMDI), there are two reports of developmental toxicity tests with pregnant rats (Wistar) exposed by inhalation during the organogenesis period (gestational days 6-15). In one report, it is reported that no abnormality was observed in the fetuses at 12 mg/m3 where maternal toxicity (decreased food consumption, increased lung weight) was observed (CICAD 27 (2000), EU-RAR (2005)). In the other report, it is reported that a low value of body weight, an increase in frequency of skeletal variations, and retarded ossification were observed in the fetuses at 12 mg/m3 where deaths (2/25) and decreased placenta weight were observed in maternal animals (CICAD 27 (2000), IRIS Tox Review (1998), EU-RAR (2005)). |
| 8 | Specific target organ toxicity - Single exposure | Category 1 (respiratory organs) |
Danger |
H370 | P308+P311 P260 P264 P270 P321 P405 P501 |
This substance is irritating to the respiratory tract (DFGOT Vol. 8 (1997), IARC 71 (1999)). As for experimental animals, a decreased respiratory rate and an increased respiratory volume in an inhalation exposure (doses corresponding to Category 1) in guinea pigs, and in an inhalation exposure (doses corresponding to Category 1) in rats, at autopsy just after exposure, hemorrhage and oedema in the lungs were observed (CICAD 27 (2000)). From the above, this substance was classified in Category 1 (respiratory organs) because it has effects on the respiratory organs. |
| 9 | Specific target organ toxicity - Repeated exposure | Category 1 (respiratory organs) |
Danger |
H372 | P260 P264 P270 P314 P501 |
There is a description that in research on 18 workers at a timber product plant using heated MDI, lower respiratory tract symptoms were observed, and later, after the symptom onset time was corrected for confounding factors, it was shown that they were occupational asthma and developed due to exposure to the vapor from heating this substance over 2.5 years or longer. The causative agent of sensitization by MDI is assumed to be either reaction products of the vapour and polymers of MDI, MDI alone, or a mixture of MDI and the reactive products (CICAD 27 (2000)). In addition, it is reported that as a result of necropsy of a foundry worker who was diagnosed with asthma induced by this substance five years before the death, and continued exposure to this substance, morphological changes such as epithelial desquamation, eosinophilic and neutrophilic infiltration, oedema, and dilatation of the bronchial vessels were observed in the lung (CICAD 27 (2000)). As for experimental animals, there is a description that in a 2-year test in which female rats were exposed by inhalation to this substance (purity 99.5%), increased lung weight, focal or multifocal alveolar/bronchiolar epithelial hyperplasia, interstitial fibrosis, an accumulation of particle-laden macrophages, and decreased pulmonary function were observed at doses within the range of Category 1 (0.23-2.05 mg/m3: (converted guidance value: 0.00047-0.0041 mg/L/6 hr/day)) (CICAD 27 (2000)). In addition, there are the following descriptions on a study in which rats were exposed by inhalation to PMDI containing 52% MDI monomer and 30% isocyanate for 13 weeks or 2 years: in the 13-week test, atrophy and degeneration of nasal cavity tissues, and an accumulation of macrophages in the lungs and mediastinal lymph nodes were observed at 4.1-12.3 mg/m3 corresponding to Category 1, and at high concentrations, severe respiratory symptoms occurred, and 25% (15/60) of animals died (CICAD 27 (2000), DFGOT Vol. 8 (1997)); and in the 2-year exposure, at or above 0.98 mg/m3, the effects were seen only in the respiratory organs, and findings were observed in the nasal cavity (degeneration of the olfactory epithelia, hyperplasia of the basal cells), lung (fibrosis, interstitial pneumonitis), and mediastinal lymph nodes (CICAD 27 (2000), DFGOT Vol. 8 (1997)). From the above, it was classified in Category 1 (respiratory organs). |
| 10 | Aspiration hazard | Classification not possible |
- |
- | - | Classification not possible due to lack of data. Besides, the kinematic viscosity of this substance is calculated to be 3.547 mm2/sec (50/20 deg C) from the numerical data (viscosity: 4.7 mPa*s (50 deg C), density (specific gravity): 1.325 (20 deg C)) listed on EU-RAR (2005). |
| Hazard class | Classification | Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | |
|---|---|---|---|---|---|---|
| 11 | Hazardous to the aquatic environment (Acute) | Classification not possible |
- |
- | - | No data available. |
| 11 | Hazardous to the aquatic environment (Long-term) | Classification not possible |
- |
- | - | No data available. |
| 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. |