GHS Classification Result
GENERAL INFORMATION
REFERENCE INFORMATION
PHYSICAL HAZARDS
HEALTH HAZARDS
ENVIRONMENTAL HAZARDS
NOTE:
GENERAL INFORMATION
| Item | Information |
|---|---|
| CAS RN | 872-50-4 |
| Chemical Name | N-Methyl-2-pyrrolidone [N-methylpyrrolidone] |
| Substance ID | H27-B-027/C-048B_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 | FY2008 |
| 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 present in the molecule associated with explosive properties. |
| 2 | Flammable gases (including chemically unstable gases) | Not applicable |
- |
- | - | "Liquids" according to GHS definition. |
| 3 | Aerosols | Not applicable |
- |
- | - | Not an aerosol product. |
| 4 | Oxidizing gases | Not applicable |
- |
- | - | "Liquids" according to GHS definition. |
| 5 | Gases under pressure | Not applicable |
- |
- | - | "Liquids" according to GHS definition. |
| 6 | Flammable liquids | Category 4 |
Warning |
H227 | P370+P378 P403+P235 P210 P280 P501 |
Based on a flash point of 86 degrees C (closed cup) (ICSC (2014)), it was classified in Category 4. |
| 7 | Flammable solids | Not applicable |
- |
- | - | "Liquids" according to 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 ignition point of 346 degrees C (HSDB (Access on June 2015)). |
| 10 | Pyrophoric solids | Not applicable |
- |
- | - | "Liquids" according to GHS definition. |
| 11 | Self-heating substances and mixtures | Classification not possible |
- |
- | - | No established test method suitable for liquid substances. |
| 12 | Substances and mixtures which, in contact with water, emit flammable gases | Not applicable |
- |
- | - | Not containing metals or metalloids (B, Si, P, Ge, As, Se, Sn, Sb, Te, Bi, Po, At). |
| 13 | Oxidizing liquids | Not applicable |
- |
- | - | It is an organic compound which does not contain fluorine or chlorine but contains oxygen, and the oxygen is not chemically bonded to the elements other than carbon or hydrogen. |
| 14 | Oxidizing solids | Not applicable |
- |
- | - | "Liquids" according to GHS definition. |
| 15 | Organic peroxides | Not applicable |
- |
- | - | It is an organic compound that does not contain bivalent -O-O- structure in the molecule. |
| 16 | Corrosive to metals | Classification not possible |
- |
- | - | Due to no data, the classification is not possible. |
| Hazard class | Classification | Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | |
|---|---|---|---|---|---|---|
| 1 | Acute toxicity (Oral) | Not classified |
- |
- | - | Nine LD50 values of 3,500 mg/kg, 3,600 mg/kg, 3,800 mg/kg (DFGOT vol. 10 (1998)), 3,605 mg/kg (SIDS (2009)), 3,914 mg/kg (Result of the initial environmental risk assessment of chemicals, Ministry of the Environment in Japan: Tentative hazard assessment sheet, Vol. 8 (2010); SIDS (2009)), 4,150 mg/kg (SIDS (2009), CICAD 35 (2001), DFGOT vol. 10 (1998)), 4,320 mg/kg (PATTY (6th, 2012); Rationale for setting the Recommendation of Acceptable Concentration of the Japan Society for Occupational Health (2002)), 4,850 mg/kg, and 7,900 mg/kg (DFGOT vol. 10 (1998)) were reported for rats. All correspond to "Not classified," and it was classified as "Not classified" (Category 5 in UN GHS classification) to which eight data correspond. |
| 1 | Acute toxicity (Dermal) | Not classified |
- |
- | - | From reported LD50 values of > 5,000 mg/kg (SIDS (2009)) and 7,000 mg/kg (SIDS (2009), DFGOT vol. 10 (1998)) for rats, and a reported LD50 value of 6,000 mg/kg for rabbits (DFGOT vol. 10 (1998)), it was classified as "Not classified." |
| 1 | Acute toxicity (Inhalation: Gases) | Not applicable |
- |
- | - | "Liquids" according to GHS definition. |
| 1 | Acute toxicity (Inhalation: Vapours) | Classification not possible |
- |
- | - | Due to lack of data, the classification is not possible. |
| 1 | Acute toxicity (Inhalation: Dusts and mists) | Not classified |
- |
- | - | From a reported LC50 value (4 hours) of > 5.1 mg/L for rats (SIDS (2009), CICAD 35 (2001), DFGOT vol. 10 (1998)), it was classified as "Not classified." Besides, because it is written that the test was conducted on aerosols, and the LD50 value is higher than the saturated vapour pressure concentration (1.3 mg/L), a reference value of mists was applied. |
| 2 | Skin corrosion/irritation | Category 2 |
 Warning |
H315 | P302+P352 P332+P313 P362+P364 P264 P280 P321 |
It is reported that in a Draize test using rabbits, slight erythema (Draize score: 1) was observed after 24-hour occlusive application of 0.5 mL undiluted this substance (purity > 98 %), and a primary irritation index (PII) was 0.5 (maximum 8) (SIDS (2009), CICAD 35 (2001), DFGOT vol.10 (1998)). On the other hand, severe erythema and scaling were observed after this substance was applied to rabbit skin for 5-15 minutes, and severe edema was found after additional 20-hour application (DFGOT vol.10 (1998), SIDS (2009)). However, In SIDS, this report which is unreliable was not adopted, and it is concluded that this substance is slightly irritating to rabbits (SIDS SIAP (2009)). Moreover, it is reported that slight to moderate transient irritation occurred when 24-hour patch application of this substance to abraded skin of 50 people was done 15 times in total (SIDS (2009), CICAD 35 (2001)). Besides, in occupational exposure, skin signs such as redness and itching were reported in workers handling this substance (Rationale for setting the Recommendation of Acceptable Concentration of the Japan Society for Occupational Health (2002)), but the details such as reversibility are unknown. From the above, although there is the report corresponding to "Not classified" in animal tests, because moderate irritation was reported in humans, the substance was classified in Category 2. Besides, it is classified in "Skin. Irrit. 2 H315" in EU CLP classification (ECHA CL Inventory (Access on September 2015)). |
| 3 | Serious eye damage/eye irritation | Category 2A |
Warning |
H319 | P305+P351+P338 P337+P313 P264 P280 |
It is reported that in a Draize test using rabbits, after 0.1 mL of undiluted this substance (purity> 98 %) was applied, corneal irritation (primary irritation index: washed eyes; 0-35, unwashed eyes; 0-41) was observed but resolved within 21 days (SIDS (2009), CICAD 35 (2001)). Moreover, it is reported that in other eye irritation tests using rabbits, corneal opacity, redness, and swelling were observed and persisted after eight days (DFGOT vol.10 (1998)), and moderate to severe irritation was observed (DFGOT vol.10 (1998)). From the above results, the substance was classified in Category 2A. Besides, it is classified in "Eye. Irrit. 2 H319" in EU CLP classification (ECHA CL Inventory (Access on September 2015)). |
| 4 | Respiratory sensitization | Classification not possible |
- |
- | - | Due to lack of data, the classification is not possible. |
| 4 | Skin sensitization | Classification not possible |
- |
- | - | The classification is not possible due to lack of data. Besides, it is reported that sensitization was not observed in a sensitization test using guinea pigs (SIDS (2009), CICAD 35 (2001), DFGOT vol.10 (1998)), and it is written that sensitization was not found when 24-hour patch application of this substance to abraded skin of 50 people was conducted 15 times in total (SIDS (2009), CICAD 35 (2001), DFGOT vol. 10 (1998)), but details such as test conditions are unknown for both. On the other hand, in occupational exposure, contact dermatitis, skin signs and so on were reported in workers handling this substance (Rationale for setting the Recommendation of Acceptable Concentration of the Japan Society for Occupational Health (2002)). By reviewing information, the Category was changed. |
| 5 | Germ cell mutagenicity | Classification not possible |
- |
- | - | Becaus it was not possible to classify a substance as "Not classified" according to the revised GHS classification guidance for the Japanese government, it was classified as "Classification not possible." As for in vivo, it is reported that a dominant lethal test in mice was negative, and a micronucleus test in bone marrow cells of mice and Chinese hamsters and a chromosomal aberration test in bone marrow cells of Chinese hamsters were negative (CICAD 35 (2001); SIDS (2009); Rationale for setting the Recommendation of Acceptable Concentration of the Japan Society for Occupational Health (2002); PATTY (6th, 2012); DFGOT vol. 10 (1998)). As for in vitro, a bacterial reverse mutation test, and a gene mutation test, a chromosomal aberration test, an unscheduled DNA synthesis test in cultured mammalian cells were all negative (CICAD 35 (2001); SIDS (2009); PATTY (6th, 2012), DFGOT vol. 10 (1998); Rationale for setting the Recommendation of Acceptable Concentration of the Japan Society for Occupational Health (2002); NTP DB (Access on August 2015)). |
| 6 | Carcinogenicity | Classification not possible |
- |
- | - | There is no carcinogenicity information in humans. As for experimental animals, evidence of tumor induction was not shown in a carcinogenicity test using rats in 2-year exposure in inhalation and oral routes (in the diet) (SIDS (2009)). On the other hand, it is written that in a carcinogenicity test using mice in 18-month exposure in an oral route (in the diet), hepatocellular carcinoma or adenoma in male mice, increased foci of hepatocellular alteration in males and females were observed, and increased peroxisome proliferation or cellular proliferation is suggested as mechanism of liver tumor formation in mice (SIDS (2009)). Thus, contradicting results between animal species were obtained. Furthermore, due to no classification results in carcinogenicity by other organizations, the classification is not possible due to lack of data at this time. |
| 7 | Reproductive toxicity | Category 1B |
 Danger |
H360 | P308+P313 P201 P202 P280 P405 P501 |
As for humans, in the case report on a female research assistant who is said to have this substance directly attached to the skin during washing after spill in the week 16 of pregnancy and had been in occupational exposure to this substance by the week 20 of pregnancy, diagnoses of ultrasound tests on a fetus were no abnormality in the week 13.8 of pregnancy, but delayed growth in the week 26 of pregnancy, and stillbirth was confirmed in the week 31. The person was likely to be exposed to this substance via dermal and inhalation in this case, but it is written that the relationship between exposure to this substance and a death of the fetus is unclear due to unknown exposure level and a report of the only one case. (CICAD 35 (2001); Result of the initial environmental risk assessment of chemicals, Ministry of the Environment in Japan: Tentative hazard assessment sheet, Vol. 8 (2010)) As for experimental animals, in a two-generation reproductive toxicity test using rats of two different strains in an oral route (in the diet), at a high dose where no general toxicity effects in F0 and F1 parent animals (SD strain), or weight gain reduction and decreased food consumption (Wistar strain) were observed, increased mortality and decreased weight gain were found as developmental effects in F1 and F2 offspring, but male and female parent animals of F0, F1 generations did not show reproductive toxicity effects (SIDS (2009), CICAD 35 (2001)). Moreover, in an inhalation route, in a test in which after inhalation exposure to the vapour of this substance 14 weeks before mating through a gestation period, F1 offspring born was mated on day 70 after birth with not-exposed male and female animals, in F0 generation of the highest dose (479 mg/m3), only decreased response to sound stimulation (estimated to be narcotic effects) in female parent animals and lower body weight in F1 offspring were found, but effects on F1 female or male fertility were not observed (SIDS (2009), CICAD 35 (2001)). Namely, in tests using rats in oral and inhalation routes, effects on genesis/development were observed in offspring at the dose where parent animals showed general toxicity effects, but toxic effects on sexual function and fertility in parent animals were not found. On the other hand, as developmental toxicity effects, there are results from teratogenicity tests in pregnant rats or rabbits dosed during an organogenetic period in oral, inhalation, or dermal route. In a gavage administration test, at a dose where maternal animals showed weight gain reduction in both rats and rabbits, developmental toxicity on fetuses (lower fetal weight, increased dwarf pups; rabbits had increased incidences of malformations or variations of skeleton and soft tissue) was observed (SIDS (2009), CICAD 35 (2001)). Similarly, in a developmental toxicity test in an inhalation route, only lower body weight in fetuses was found at a dose where maternal animals showed weight gain reduction and decreased food consumption in rats. In rabbits exposed to the same concentrations as in rats, no abnormality was observed in either maternal animals or fetuses except skeletal variations (extra ribs) found in fetuses of a high dose group (SIDS (2009), CICAD 35 (2001)). Furthermore, in developmental toxicity tests in a dermal route, rats showed increased deaths, lower body weight, delayed ossification, and an increased incidence of skeletal malformations in fetuses at the dose where weight gain reduction was observed in maternal animals. However, in rabbits, maternal toxicity did not occur at the doses up to 1,000 mg/kg/day, and only skeletal variations (extra ribs) were found in fetuses (SIDS (2009), CICAD 35 (2001)). As above, in a reproductive toxicity test using rats in oral and inhalation routes, parent animals did not show effects on fertility even dosed up to the dose where general toxicity effects were found in parent animals. However, in developmental toxicity tests in pregnant animals in administration during an organogenetic period, in an oral route, both in rats and rabbits, developmental toxicity effects including skeletal malformations were observed in fetuses at the dose where maternal toxicity occurred. Skeletal malformations were also found in tests in rats in a dermal route and were findings observed in fetuses at the dose where maternal toxicity such as weight gain reduction occurred. By taking into account the information that fetal toxicity and malformations were not secondary effects of maternal toxicity (SIDS (2009)), skeletal malformation formation was judged to be findings suggesting serious reproductive toxicity effects of administering this substance. Therefore, the substance was classified in Category 1B in this hazard class. Besides, it is classified in Repr. 1B in EU CLP classification, from which EU designated this substance in "substances of very high concern" (SVHC) (ECHA CL Inventory (Access on June 2015)). |
| 8 | Specific target organ toxicity - Single exposure | Category 3 (Narcotic effects) |
Warning |
H336 | P304+P340 P403+P233 P261 P271 P312 P405 P501 |
Respiratory tract irritation was observed for this substance in experimental animals. As for humans, severe eye irritation and headache were found, but in an inhalation test in volunteers and so on, it is reported that it is not irritating to the respiratory tract (CICAD 35 (2001), SIDS (2009), PATTY (6th, 2012), DFGOT vol. 10 (1998)). As for experimental animals, deaths were not observed in inhalation exposure to 5,100 mg/m3 (5.1 mg/L) (a vapour/aerosol mixture) in rats, and tachypnea, irregular respiration, shortness of breath, and decreased pain reflex during exposure, and tachypnea after exposure were found. Incoordination was reported in oral administration at 519 mg/kg in rats and mice (CICAD 35 (2001)). From the above information, it was judged to be not irritating to the respiratory tract in humans. Moreover, because rats showed decreased pain reflex and incoordination, narcotic effects were thought. From the above, the substance was classified in Category 3 (narcotic effects). By adding new information, the previous classification was revised. |
| 9 | Specific target organ toxicity - Repeated exposure | Category 2 (nervous system, lung, liver, bone marrow) |
Warning |
H373 | P260 P314 P501 |
There is no human information. Toxicity in inhalation exposure is affected largely by a ratio of aerosol to vapour and an exposure range (head-only or whole-body exposure) (CICAD 35 (2001)). As for experimental animals, in a 2-week inhalation toxicity test using rats, head-only exposure to 1,000 mg/m3 (converted to a Guidance value equivalent: 0.11 mg/L) caused only slight nasal irritation, but after whole-body exposure to the same concentration with coarse droplets at high humidity, markedly increased mortality (8-9/10 animals), apathy, irregular respiration, convulsion, tremor, decreased body weight/weight gain, and nasal irritation were observed, and dead animals showed serious effects on organs/tissue (congestion in nearly all organs, depletion and necrosis of lymphocytes in the spleen, panmyelophthisis, gelatinous bone marrow, and cell depletion in bone marrow, pulmonary edema and multifocal purulent pneumonia in the lung, necrotic alteration in the liver, ulcer in the glandular stomach, increased adrenal weight) (CICAD 35 (2001)). Moreover, in a 4-week repeated inhalation toxicity test using rats (exposure was stopped after 10 days for a high dose due to many deaths observed), at 1,000 mg/m3 (converted to a Guidance value equivalent: 0.11 mg/L) deaths or slaughtering moribund animals (13/30), lethargy, irregular respiration, and dyspnea were observed, and dead/moribund animals showed edema/congestion in the lung, bone marrow hypoplasia, atrophy and necrosis of the lymphoid tissue of thymus, spleen, and lymph nodes (Result of the initial environmental risk assessment of chemicals, Ministry of the Environment in Japan: Tentative hazard assessment sheet, Vol. 8 (2010); Rationale for setting the Recommendation of Acceptable Concentration of the Japan Society for Occupational Health (2002); CICAD 35 (2001)). The maximum vapour phase concentration at room temperature is 1,318 mg/m3 in dry air (0% relative humidity), 412 mg/m3 at normal humidity (60% relative humidity), 0 mg/m3 in wet air (100% relative humidity) (CICAD 35 (2001)). Therefore, 1,000 mg/m3 mentioned above is thought to contain mists but not vapour, and by applying the category for mists, the substance was classified in Category 2 (nervous system, lung, liver, bone marrow). Besides, in an oral route, in multiple repeated oral administration toxicity tests using rats, low arousal, palpebral closure, abnormality in neurobehavioral test, bone marrow hypoplasia, atrophy of thymus, centrilobular hepatocellular hypertrophy, centrilobular fatty degeneration in the liver, degeneration/atrophy of testis, decreased lymphoid cells in mesenteric lymph nodes, chronic progressive nephropathy (males), thickening/cyst formation in adrenal cortex were found, and effects on central nervous system, bone marrow, liver, testis, kidney, and adrenal were observed. These findings were above a range of Category 2. Category for vapour was applied in the previous classification, but because category for mists was applied due to the reason mentioned above, the Category was changed. Moreover, the data from a 5-month inhalation test mentioned in DFGOT vol.10 (1998) was adopted for the previous classification, but it is written in DFGOT vol.10 (1998) that because changes in the spleen, liver, lung, and kidney were found at extremely low concentrations of 100-200 mg/m3, these findings are questionable. Therefore, the data were not adopted. |
| 10 | Aspiration hazard | Classification not possible |
- |
- | - | The classification is not possible due to lack of data. Besides, kinematic viscosity is calculated to be 1.61 mm2/sec (25 degrees C) from numerical data listed in HSDB (viscosity: 1.65 mPa*s (25 degrees C), density (specific gravity): 1.027) (HSDB (Access on June 2015)). |
| Hazard class | Classification | Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | |
|---|---|---|---|---|---|---|
| 11 | Hazardous to the aquatic environment (Acute) | Not classified |
- |
- | - | From 72-hour EC50 > 500 mg/L for algae (Desmodesmus subspicatus), 24-hour EC50 > 1000 mg/L for crustacea (Daphnia magna), and 96-hour LC50 > 500 mg/L for fish (Oncorhynchus mykiss) (all SIDS, 2009), it was classified as "Not classified." |
| 11 | Hazardous to the aquatic environment (Long-term) | Not classified |
- |
- | - | If chronic toxicity data are used, then it is classified as "Not classified" due to rapid degradability (a degradation rate by 28-day BOD (NO2) = 73%, a degradation rate by BOD (NH3) = 94%, a degradation rate by TOC = 96%, a degradation rate by GC = 100% (Official Bulletin of Ministry of International Trade and Industry, 1989)), and 21-day NOEC (reproduction and lethal) = 12.5 mg/L for crustacea (Daphnia magna) (all SIDS, 2009). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained, then it is classified as "Not classified" due to corresponding to "Not classified" in acute toxicity for fish, and not water-insoluble (water solubility = 100,000 mg/L, PHYSPROP Database 2009). It was classified as "Not classified" from the above results. |
| 12 | Hazardous to the ozone layer | Classification not possible |
- |
- | - | No data. |
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. |