NITE - Chemical Management Field

Latest GHS Classification Results by the Japanese Government (edited by NITE)

GENERAL INFORMATION

Item	Information
CAS RN	110-89-4
Chemical Name	piperidine
Substance ID	m-nite-110-89-4_v1
Download of Excel format	Excel file

REFERENCE INFORMATION

Item	Information
Guidance used for the classification (External link)	To Guidance List
UN GHS document (External link)	To UN GHS document
FAQ（GHS classification results by the Japanese Government）	To FAQ
List of Information Sources (Excel file)	List of Information Sources
List of Definitions/Abbreviations	Definitions/Abbreviations
Sample Label by MHLW (External link)	MHLW Website (in Japanese Only)
Sample SDS by MHLW (External link)	MHLW Website (in Japanese Only)
OECD/eChemPortal (External link)	To OECD/eChemPortal (External link)

PHYSICAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification	Classification year (FY)	GHS Classification Guidance for the Japanese Government
1	Explosives	Not classified (Not applicable)	- -	-	-	There are no chemical groups associated with explosive properties present in the molecules.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
6	Flammable liquids	Category 2	Danger	H225	P303+P361+P353 P370+P378 P403+P235 P210 P233 P240 P241 P242 P243 P280 P501	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)).	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
7	Flammable solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
8	Self-reactive substances and mixtures	Not classified (Not applicable)	- -	-	-	There are no chemical groups present in the molecule associated with explosive or self-reactive properties.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
9	Pyrophoric liquids	Not classified	- -	-	-	Its autoignition point is 365degC (Hommel (1996)), which is above 70degC.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
10	Pyrophoric solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Test methods applicable to liquid substances are not available.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
12	Substances and mixtures which, in contact with water, emit flammable gases	Not classified (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).	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	Organic compounds containing no oxygen, fluorine or chlorine	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Organic compounds containing no bivalent -O-O- structure	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
16	Corrosive to metals	Classification not possible	- -	-	-	No data available.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
17	Desensitized explosives	-	- -	-	-	-	-	-

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification	Classification year (FY)	GHS Classification Guidance for the Japanese Government
1	Acute toxicity (Oral)	Category 4	Warning	H302	P301+P312 P264 P270 P330 P501	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.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
1	Acute toxicity (Dermal)	Category 3	Danger	H311	P302+P352 P361+P364 P280 P312 P321 P405 P501	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.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
1	Acute toxicity (Inhalation: Gases)	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
1	Acute toxicity (Inhalation: Vapours)	Category 3	Danger	H331	P304+P340 P403+P233 P261 P271 P311 P321 P405 P501	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.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	No data available.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
2	Skin corrosion/irritation	Category 1	Danger	H314	P301+P330+P331 P303+P361+P353 P305+P351+P338 P304+P340 P260 P264 P280 P310 P321 P363 P405 P501	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.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
3	Serious eye damage/eye irritation	Category 1	Danger	H318	P305+P351+P338 P280 P310	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.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
4	Respiratory sensitization	Classification not possible	- -	-	-	No data available.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
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.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
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)).	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 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.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
7	Reproductive toxicity	Category 2	Warning	H361	P308+P313 P201 P202 P280 P405 P501	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.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
8	Specific target organ toxicity - Single exposure	Category 1 (central nervous system)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	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).	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
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.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
10	Aspiration hazard	Classification not possible	- -	-	-	No data available.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）

ENVIRONMENTAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification	Classification year (FY)	GHS Classification Guidance for the Japanese Government
11	Hazardous to the aquatic environment Short term (Acute)	Classification not possible	- -	-	-	No data available.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
11	Hazardous to the aquatic environment Long term (Chronic)	Classification not possible	- -	-	-	No data available.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
12	Hazardous to the ozone layer	-	- -	-	-	-	-	-

NOTE:

GHS Classification Result by the Japanese Government is intended to provide a reference for preparing a GHS label or SDS for users. To include the same classification result in a label or SDS for Japan is NOT mandatory.
Users can cite or copy this classification result when preparing a GHS label or SDS. Please be aware, however, that the responsibility for a label or SDS prepared by citing or copying this classification result lies with users.
This GHS classification was conducted based on the information sources and the guidance for classification and judgement which are described in the GHS Classification Guidance for the Japanese Government etc. Using other literature, test results etc. as evidence and including different content from this classification result in a label or SDS are allowed.
Hazard statement and precautionary statement will show by hovering the mouse cursor over a code in the column of "Hazard statement" and "Precautionary statement," respectively. In the excel file, both the codes and statements are provided.
A blank or "-" in the column of "Classification" denotes that a classification for the hazard class was not conducted in the year.
An asterisk “*” in the column of “Classification” denotes that “Not classified (or No applicable)” and/or “Classification not possible” is applicable. Details are described in the column of “Rationale for the classification”. If no English translation is available for “Rationale for the classification,” please refer to the Japanese version of the results.

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