GHS Classification Result

Chemical Name：piperidine
CAS：110-89-4

Result：
ID: 20A2173
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 2 Danger H225: Highly flammable liquid and vapour P303+P361+P353: IF ON SKIN （or hair）: Remove/Take off immediately all contaminated clothing. Rinse skin with water/shower.
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.
P233: Keep container tightly closed.
P240: Ground/bond container and receiving equipment.
P241: Use explosion-proof electrical/ventilating/lighting/.../equipment.
P242: Use only non-sparking tools.
P243: Take precautionary measures against static discharge.
P280: Wear protective gloves/protective clothing/eye protection/face protection.
P501: Dispose of contents/container to ... 		Its flash point is 4-16degC (Gangolli (2nd. 1999), ICSC (J) (2003)), which is lower than 23degC; its initial boiling point must be above 35degC given that it is a single substance with its boiling point at 106degC (Merck (14th, 2006)).
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 365degC (Hommel (1996)), which is 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 - - - - 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
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） Category 4 Warning H302: Harmful if swallowed P301+P312: IF SWALLOWED: Call a POISON CENTER or doctor/physician if you feel unwell.
P264: Wash ... thoroughly after handling.
P270: Do not eat, drink or smoke when using this product.
P330: Rinse mouth.
P501: Dispose of contents/container to ... 		Of three rat LD50 values (133 mg/kg, 447 mg/kg, and 337 mg/kg) found in List 1 documents (PATTY (5th, 2001)), two values fell under Category 4.
1 Acute toxicity （Dermal） Category 3 Danger H311: Toxic in contact with skin P302+P352: IF ON SKIN: Wash with plenty of soap and water.
P280: Wear protective gloves/protective clothing/eye protection/face protection.
P312: Call a POISON CENTER or doctor/physician if you feel unwell.
P322: Specific treatment （see ... on this label）.
P361: Remove/Take off immediately all contaminated clothing.
P363: Wash contaminated clothing before reuse.
P405: Store locked up.
P501: Dispose of contents/container to ... 		There were no LD50 value for rats and two LD50 values for rabbits reported in List 1 document (257 mg/kg and 1000 mg/kg) (PATTY (5th, 2001)). The lower value of two rabbit LD50 values was selected as grounds for classification of the substance into Category 3.
1 Acute toxicity （Inhalation: Gases） Not applicable - - - - Liquid (GHS definition)
1 Acute toxicity （Inhalation: Vapours） Category 3 Danger H331: Toxic if inhaled 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.
P311: Call a POISON CENTER or doctor/physician.
P321: Specific treatment （see ... on this label）.
P405: Store locked up.
P501: Dispose of contents/container to ... 		Among its rat LC50 of < 4000 ppm/4h (PATTY (5th, 2001)) and > 2000 ppm (HSDB (2008)), and mouse LC50 of 1723 ppm/4h (= 860 ppm/4h) (PATTY (5th, 2001)), the mouse LD50 value was selected as grounds for classification of the substance into Category 3. Given that its vapour pressure is 30 mbar at 20degC (Hommel (1996)), its saturated concentration is approximately 30000 ppm. Based on this information, the study was presumably conducted in a vapour state with almost no included mists.
1 Acute toxicity （Inhalation: Dusts and mists） Classification not possible - - - - No data available.
2 Skin corrosion/irritation Category 1 Danger H314: Causes severe skin burns and eye damage P301+P330+P331: IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P303+P361+P353: IF ON SKIN （or hair）: Remove/Take off immediately all contaminated clothing. Rinse skin with water/shower.
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P304+P340: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P260: Do not breathe dust/fume/gas/mist/vapours/spray.
P264: Wash ... thoroughly after handling.
P280: Wear protective gloves/protective clothing/eye protection/face protection.
P310: Immediately call a POISON CENTER or doctor/physician.
P321: Specific treatment （see ... on this label）.
P363: Wash contaminated clothing before reuse.
P405: Store locked up.
P501: Dispose of contents/container to ... 		In the study using 6 rabbits, necrosis was observed in all test animals (PATTY (5th, 2001)). In other animal tests, the substance was reported to have a corrosive effect (HSDB (2008)). Furthermore, in human accident cases, severe epithelial damage and chemical burns were reported with the substance in contact with skin for no longer than 3 minutes (PATTY (5th, 2001)). Based on this information on animals and humans, the substance was classified into Category 1. Its pH = 12.6 (20degC, 100 g/L) (GESTIS (accessed in November 2008)) and it is rated as R34 in the EU classification.
3 Serious eye damage/eye irritation Category 1 Danger H318: Causes serious eye damage P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P280: Wear protective gloves/protective clothing/eye protection/face protection.
P310: Immediately call a POISON CENTER or doctor/physician. 		An application of the substance to the eyes of rabbits caused irreversible injury of the cornea (PATTY (5th, 2001)). In other tests on rabbit eyes, the substance caused severe injury of the cornea, graded 9 on a scale of 1 to 10 (HSDB (2008)). Furthermore, a corrosive effect on the eyes of rabbits is also reported in a different study (HSDB (2008)). Based on these positive results, the substance was classified into Category 1. Its pH = 12.6 (20degC, 100 g/L) (GESTIS (accessed in November 2008)) and its classification for skin corrosion / irritation is Category 1.
4 Respiratory sensitization Classification not possible - - - - No data available.
4 Skin sensitization Classification not possible - - - - In four clinical cases of allergic contact dermatitis due to wearing rubber gloves, two patch-tested patients were found to be hypersensitive to piperidine, which is a constituent of the material from which the rubber gloves were made (HSDB (2008)). However, in workers handling piperidine at work, no cases of skin sensitization were observed in the period from 1989 to 1998 (HSDB (2008)). Since it is not clear if reported contact dermatitis cases are attributed to this substance, classification is not possible.
5 Germ cell mutagenicity Not classified - - - - In the mouse micronucleus test (in vivo mutagenicity tests using somatic cells), an oral administration of maximum tolerated dose of piperidine yielded negative results (HSDB (2008)). Thus, the substance was classified into the "Not classified" category. Regarding in vitro tests, Some of Ames tests and forward mutation tests using mouse lymphoma cells gave positive results (HSDB (2008)).
6 Carcinogenicity Classification not possible - - - - No indications of carcinogenicity were found in several tests in which mice received intraperitoneal injection for 6.5 weeks, rats were given 0.1% piperidine in their drinking water for 75 weeks, or rats were given 0.09% piperidine in their drinking water for 50 weeks (HSDB (2008)). However, some improper test procedures were used, which were inconsistent with the current test guidelines. For instance, only one dose was used in each of these tests, and the duration of administration was short. So, it is questionable to classify the substance into the "Not classified" category based on negative results obtained in these studies above. For that reason, the substance was classified into the "Classification not possible" category.
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 rats that underwent inhalation exposure to piperidine on day 4 of pregnancy, the number of implantation sites and the number of fetuses per female decreased as well as suppressed body weight gain being observed (all changes were statistically significant) (HSDB (2008)). In other rat tests, 4-month exposure caused altered spermatogenesis in male rats and an increase in the resorption rate in female rats (HSDB (2008)). As above, since signs of reproductive toxicity, such as decrease in the number of implantation sites and the number of fetuses per female, and an increase in the resorption rate, were observed at the doses that induce general toxicity in parental animals, the substance was classified into Category 2.
8 Specific target organ toxicity - Single exposure Category 1 (central nervous system) Danger H370: Causes damage to organs (central nervous system) P307+P311: IF exposed: Call a POISON CENTER or doctor/physician.
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.
P321: Specific treatment （see ... on this label）.
P405: Store locked up.
P501: Dispose of contents/container to ... 		After oral administration, weakness, respiratory distress, and convulsions were seen in rats treated with 100 mg/kg (PATTY (5th, 2001)). In other study, toxic symptoms such as decreased motor activity, tremors, and respiratory effects were noted at 5-2000 mg/kg; and decreased motor activity, tremors, respiratory effects, ataxia, and salivation were noted at doses around the LD50 value (337 mg/kg) (HSDB (2008)). It is documented that piperidine causes excitation or inhibition of synapses in the central nervous system (GESTIS (accessed in November 2008)). Overall, this substance presumably induces toxic symptoms in the nervous system, and these symptoms appear at doses as low as 100 mg/kg. As such, the substance was classified into Category 1 (central nervous system).
9 Specific target organ toxicity - Repeated exposure Classification not possible - - - - In rats or rabbits that received repeated inhalation exposure to piperidine 4 hours a day for 4 months showed the following changes at 0.01 mg/L (2.87 ppm) (6 hours/day-correction value: 0.008 mg/L or 2.34 ppm): renal dysfunction (lower daily diuresis), scars in the myocardium including necrotic areas, thickening of alveolar walls, protein dystrophy in the liver, hyaline droplet degeneration in the kidneys (HSDB (2008)). On the other hand, in the 4-week repeated inhalation exposure study using rats (OECD TG 412), except for a slight increase in relative liver weights and a tendency towards retardation of body weight gain being observed at 0.348 mg/L (100 ppm) (90-day correction value: 0.107 mg/L or 30.8 ppm), no effects of the substance, including neurotoxic effects, were detected (HSDB (2008)). Overall, while various adverse effects were observed in the 4-month study, they were not shown in the 4-week study in spite of the use of the high exposure concentration (0.107 mg/L), more than 10 times the concentration used in the 4-month test (0.008 mg/L). Since these results and data remain questionable in terms of their consistency and validity, the substance was classified into the "Classification not possible" category.
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） Classification not possible - - - - No data available.
11 Hazardous to the aquatic environment （Long-term） Classification not possible - - - - No data available.


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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