GHS Classification Result

Chemical Name：N-methyl-2-pyrrolidone
CAS：872-50-4

Result：
ID: 20A2059
Classifier: Ministry of Health, Labour and Welfare （MHLW）, Ministry of the Environment （MOE）
Year Classified: FY2008
Reference Manual: GHS Classification Guidance by the Japanese Government （Sep, 2008）

PHYSICAL HAZARDS
Hazard class Classification Symbol Signal word Hazard statement Precautionary statement Rationale for the classification
1 Explosives Not applicable - - - - There are no chemical groups associated with explosive properties present in the molecules.
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: Combustible liquid P370+P378: In case of fire: Use ... for extinction.
P403+P235: Store in a well-ventilated place. Keep cool.
P210: Keep away from heat/sparks/open flames/hot surfaces. ? No smoking.
P280: Wear protective gloves/protective clothing/eye protection/face protection.
P501: Dispose of contents/container to ... 		Its flash point is 92.78degC (converted value) (Merck 14th, 2006) or 86degC (Solvents Handbook, Ohmsha Ltd., 1994) in a closed system. Based on the information, the substance was classified into Catgory 4.
7 Flammable solid 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 - - - - Its autoignition point is 346degC (Chapman ver.16:1, 2008) or 245degC (DIN51794) (Ullmanns (E) 6th, 2003, vol.30), which are above 70degC.
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 - - - - The substance contains oxygen (but not fluorine or chlorine) which is chemically bonded only to carbon or hydrogen.
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 Symbol Signal word Hazard statement Precautionary statement Rationale for the classification
1 Acute toxicity （Oral） Not classified - - - - The rat LD50 values have been documented as 4150 mg/kg (CICADs (J) No.35, 2001), 3500, 3600, 3800, 4850, 7900 mg/kg (DFGOT vol.10, 1998), and 4320mg/kg bw (PATTY 5th vol.4, 2001). Based on these values, the substance was classified into "Not classified" (JIS). All of the seven LD50 values but 7900mg/kg are equivalent to the Category 5 guidance values of the United Nations classification. Thus, the substance was classified into Category 5 in the United Nations classification.
1 Acute toxicity （Dermal） Not classified - - - - The rat LD50 = 7000mg/kg bw (DFGOT vol.10, 1998), the rabbit LD50 = 6000mg/kg bw (DFGOT vol.10, 1998), and the rat and rabbit LD50 (details not provided) = 4000-10000mg/kg bw (CICADs (J) No.35, 2001). In addition, no mortality in rabbits and guinea pigs occurred at 2000mg/kg (PATTY 5th vol.4, 2001). Based on the information, the substance was classified into "Not classified".
1 Acute toxicity （Inhalation: Gases） Not applicable - - - - Liquid (GHS definition)
1 Acute toxicity （Inhalation: Vapours） Classification not possible - - - - According to CICADs (J) (No.35, 2001), lethal concentration for systemic exposure by aerosol, thermal vapourization, or saturated vapour was 1.7mg/L (original literature: E.L. du Pont de Nemours and Company. Four week inhalation range-finding tests on 1-methyl-2-pyrrolidone (Haskell Laboratory Report No.582-77). 1977). However, since this concentration is the saturated vapour pressure concentration, the documented tests were presumably conducted using mist. Thus, classification is not possible.
1 Acute toxicity （Inhalation: Dusts and mists） Not classified - - - - In rats that underwent head-only inhalation exposure (4 hours), mortality was not observed at 5.1mg/L (CICADs (J) No.35, 2001). Based on the saturated vapour pressure concentration of approximately 1.7mg/L, the tests were thought to be conducted under the mist state. Thus, the substance was classified into "Classification not possible".
2 Skin corrosion/irritation Category 2 Warning H315: Causes skin irritation P302+P352: IF ON SKIN: Wash with plenty of soap and water.
P332+P313: If skin irritation occurs: Get medical advice/attention.
P264: Wash ... thoroughly after handling.
P280: Wear protective gloves/protective clothing/eye protection/face protection.
P321: Specific treatment （see ... on this label）.
P362: Take off contaminated clothing and wash before reuse. 		In humans (n = 50) who repeatedly received 24-hour patch tests on scratched skin for 15 times, slight to moderate temporary irritation was induced (CICADs (J) No.35, 2001). Similarly, the substance caused skin irritation and contact dermatitis in humans (DFGOT vol.10, 1998; PATTY 5th, 2001, vol.4). In rabbit Draize tests, slight erythema (Draize score = 0.5; equivalent to "Not classified") was observed, and in topical tests in which guinea pigs were treated with an aqueous solution containing the substance, slight erythema (shown in 2 out of 10 treated guinea pigs) was observed only at 50% solution (CICADs (J) No.35, 2001). However, application of the substance to the skin of rabbits for 5 to 15 minutes caused severe erythema. Taking the skin irritation potential to humans into account, the substance was classified into Category 2.
3 Serious eye damage/eye irritation Category 2A Warning H319: Causes serious eye irritation P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P337+P313: If eye irritation persists: Get medical advice/attention.
P264: Wash ... thoroughly after handling.
P280: Wear protective gloves/protective clothing/eye protection/face protection. 		The substance has been documented to have effects on humans in such forms as severe eye irritation (CICADs (J) No.35, 2001) and chronic eye irritation (PATTY 5th, 2001, vol.4). In Draize tests on rabbits, corneal clouding, iritis, and conjunctivitis were observed, and these symptoms disappeared within 21 days (CICADs (J) No.35, 2001). Also, in another test using rabbits, corneal clouding, redness, and swelling were observed, and these symptoms continued after 8 days (DFGOT vol.10, 1998). Furthermore, in other rabbit tests, the substance was documented to cause moderate eye irritation (PATTY 5th vol.4, 2001; IUCLID, 2000). Based on these effects observed in animals and humans, the substance was classified into Category 2A.
4 Respiratory sensitization Classification not possible - - - - No data available.
4 Skin sensitization Not classified - - - - 50 humans, who repeatedly received 24-hour patch tests on scratched skin 15 times, showed no signs of contact sensitization (CICADs (J) No.35, 2001). Similarly, the substance was documented to be not sensitizing in human path tests (IUCLID, 2000). In addition, in the tests using guinea pigs, sensitization was not observed 24 and 48 hours after the application (CICADs (J) No.35, 2001). Based on the final evaluation that the substance is not sensitizing to the skin of humans and animals (CICADs (J) No.35, 2001), it was classified into "Not classified".
5 Germ cell mutagenicity Not classified - - - - Since negative results were obtained from mouse micronucleus tests and chromosomal aberration tests using Chinese hamsters (CICADs (J) No.35, 2001), the substance was classified into "Not classified". Ames tests also yielded negative results (CICADs (J) No.35, 2001; NTP DB, 2008). Although a significantly increased postimplantation loss was observed (relative to the control animals) in dominant lethal tests using mice at the concentration documented to cause toxic effects (CICADs (J) No.35, 2001), the results were disregarded as they could not be fully evaluated.
6 Carcinogenicity Classification not possible - - - - In 2-year inhalation tests using rats (DFGOT vol.10, 1998; PATTY 5th, 2001, vol.4; IUCLID, 2000), no development of tumors was observed at the high doses tested. Similarly, in the tests in which mice underwent subcutaneous injections for 17 months (PATTY 5th, 2001, vol.4; IUCLID, 2000), there was no difference in the rates of developing cancer between treated and untreated mice. However, since both inhalation route (rats) and oral route tests (mice) included only one animal species as a test subject, the substance was classified into "Classification not possible".
7 Reproductive toxicity Category 2 Warning H361: Suspected of damaging fertility or the unborn child P308+P313: IF exposed or concerned: Get medical advice/attention.
P201: Obtain special instructions before use.
P202: Do not handle until all safety precautions have been read and understood.
P281: Use personal protective equipment as required.
P405: Store locked up.
P501: Dispose of contents/container to ... 		In oral route tests using rats, the following effects were observed: decreased body weight of maternal animals, decreased survival rates and growth rates of the offspring, reduced sizes of testes and ovaries, malformation of organs and skeletons, and cryptorchism (CICADs (J) No.35, 2001). In addition, in the dermal route tests using rats, the following effects were observed: decreased body weight gain of maternal animals, increased resorption of embryos, skeletal abnormalities (lack of sternebra, fusion and split of ribs, supernumerary ribs, dysraphism of skull, failed ossification of vertebrae, fusion of cervical atlas and occipital bones, and reduction or incomplete hyoid bones). In contrast, in dermal route tests using rabbits, symptoms of maternal toxicity were not observed and only mild toxicity to fetuses (skeletal mutation: development of accessory ribs) was observed (CICADs (J) No.35, 2001). In rat inhalation tests, no effects of the substance were found on body weight of parental animals, weight of testes and ovaries, and fertility properties in 8 of 11 datasets. Neither affected were: numbers of surviving littermates, corpus luteum, implantation, dead fetuses, embryo absorption, littermates; malformation or mutation of fetuses (excluding light skeletal mutation). Yet, some data indicated that the substance caused loss of pre-implantation embryos and delayed ossification, and other data indicated that the substance had slight maternal toxicity and fetal toxicity (CICADs (J) No.35, 2001). Overall, the effects on the development of offspring were observed in both oral and dermal route exposure, and there is data indicating developmental toxicity through inhalation. Thus, the substance was classified into Category 2.
8 Specific target organ toxicity - Single exposure Category 3 （Respiratory tract irritation） Warning H335: May cause respiratory irritation (respiratory tract irritation) P304+P340: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P403+P233: Store in a well-ventilated place. Keep container tightly closed.
P261: Avoid breathing dust/fume/gas/mist/vapours/spray.
P271: Use only outdoors or in a well-ventilated area.
P312: Call a POISON CENTER or doctor/physician if you feel unwell.
P405: Store locked up.
P501: Dispose of contents/container to ... 		Since the substance is documented to cause severe eye irritation and headaches in humans (CICADs (J) No.35, 2001), it cannot be classified for specific organs or systemic toxicity. In 4-hour inhalation tests using rats, fast and irregular breathing, breathlessness, suppression of pain reflex, and bloody nasal secretion were detected. After the exposure, polypnea and slight blood trace on perinasal hair were observed (CICADs (J) No.35, 2001; DFGOT vol.10, 1998). In addition, in 2-hour inhalation tests using mice, the substance was documented to cause irritation of the eyes and upper airways (DFGOT vol.10, 1998). Based on these results, the substance was classified into Category 3 (respiratory tract irritation).
9 Specific target organ toxicity - Repeated exposure Category 1 (bone marrow, spleen, liver, respiratory system, adrenal gland, kidney) Danger H372: Cause damage to organs through prolonged or repeated exposure (bone marrow, spleen, liver, respiratory system, adrenal gland, kidney) P260: Do not breathe dust/fume/gas/mist/vapours/spray.
P264: Wash ... thoroughly after handling.
P270: Do not eat, drink or smoke when using this product.
P314: Get medical advice/attention if you feel unwell.
P501: Dispose of contents/container to ... 		In 90-day oral route tests using rats (CICADs (J) No.35, 2001), the NOAEL were 169mg/kg bw (males) and 217mg/kg bw (females). In 28-day oral route tests (CICADs (J) No.35, 2001; DFGOT vol.10, 1998; PATTY 5th, 200, vol.4), the NOAEL documented were 514mg/kg bw (90-day conversion: approx. 160mg/kg bw), 429mg/kg bw (males) (90-day conversion: approx. 133mg/kg bw), 1548mg/kg bw (females) (90-day conversion: approx. 482mg/kg bw); all these values were equivalent to the "Not classified" guidance values. In 20-day oral route tests using rabbits (DFGOT vol.10, 1998), no effects were observed on organs. In 13-week inhalation tests using rats (aerosol or mist) (CICADs (J) No.35, 2001; DFGOT vol.10, 1998), the effects on testes and the blood were observed. However, the administration dose was 3mg/L, which was equivalent to the "Not classified" guidance values. Similarly, in 4-week inhalation tests (aerosol or mist) (CICADs (J) No.35, 2001; DFGOT vol.10, 1998; PATTY 5th, 200, vol.4), the administration dose (90-day conversion: approx. 0.3mg/L), was equivalent to the "Not classified" guidance values. On the other hand, in another 2-week inhalation test using rats (assuming that the substance was in vapour state based on the administration dose of 1.0mg/L) (CICADs (J) No.35, 2001), 90-day conversion value of approx. 0.16mg/L (equivalent to Category 1 guidance values) was associated with reduction and necrosis of the bone marrow cells and the spleen (lymphocytes), necrosis of the liver, multifocal purulent pneumonia, ulceration of glandular stomach, and increased weight of adrenal glands. Moreover, in 5-month inhalation tests (assuming that the substance was in vapour state based on the administration dose of 0.1-0.15mg/L) (DFGOT vol.10, 1998), changes in the lung and kidney were observed at the dose equivalent to the Category 1 guidance values. Thus, the substance was classified into Category 1 (bone marrow, spleen, liver, respiratory system, adrenal gland, and kidney) for inhalation route only.
10 Aspiration hazard Classification not possible - - - - No data available.

ENVIRONMENTAL HAZARDS
Hazard class Classification Symbol Signal word Hazard statement Precautionary statement Rationale for the classification
11 Hazardous to the aquatic environment （Acute） Not classified - - - - Since its toxic values are > 100mg/L for algae (Scenedesmus), crustaceans (Daphnia magna), and fish (rainbow trout) (SIDS, 2007), the substance was classified into "Not classified".
11 Hazardous to the aquatic environment （Long-term） Not classified - - - - As it is water soluble (water solubility: 1000000mg/L (SRC, 2005)) and its classification for acute toxicity is "Not classified", the substance was classified into "Not classified".


NOTE:
* 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.

Reference：
Reference Manual
Definitions / Abbreviations
Model Label by MHLW

 MHLW Website （in Japanese Only）
Model SDS by MHLW

 MHLW Website （in Japanese Only）

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