NITE - Chemical Management Field

GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	55-63-0
Chemical Name	Nitroglycerin
Substance ID	24B6512
Classification year (FY)	FY2012
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)	Physical Hazards and Health Hazards: GHS Classification Guidance by the Japanese Government (July, 2010) Environmental Hazards: UN GHS Document (4th revised edition)
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

PHYSICAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Explosives	Unstable Explosive	Danger	H200	P201 P202 P280 P372 P373 P380 P401 P501	Transportation of the pure substance is prohibited in UNRTDG. Besides, the diluted product is classified in Division 1.1D.
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	Classification not possible	- -	-	-	No data available.
7	Flammable solids	Not applicable	- -	-	-	Liquid (GHS definition)
8	Self-reactive substances and mixtures	Not applicable	- -	-	-	It was classified in explosives (unstable explosives).
9	Pyrophoric liquids	Not classified	- -	-	-	It is estimated that it does not ignite at normal temperatures from an autoignition temperature of 270 deg C (ICSC (J) (2005)).
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	Classification not possible	- -	-	-	The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is chemically bonded to the element other than carbon or hydrogen (N). However, the classification is not possible due to no data.
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	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Acute toxicity (Oral)	Category 4	Warning	H302	P301+P312 P264 P270 P330 P501	Among three LD50 values reported for rats [685 mg/kg (USEPA/HPV (2002); corresponding to List 1), 822-884 mg/kg (Initial Risk Assessment Report Ver. 1.0, 139 (NITE, CERI, NEDO, 2008)), and 105 mg/kg (Environmental Risk Assessment for Chemical Substances vol. 7 (Ministry of the Environment, 2009))], one corresponds to Category 3, and two correspond to Category 4. Therefore, it was classified in Category 4 to which most corresponded.
1	Acute toxicity (Dermal)	Not classified	- -	-	-	It was classified as "Not classified" based on an LD50 value of > 9,560 mg/kg for rats (OECD TG402, GLP-compliant) (USEPA/HPV (2002)).
1	Acute toxicity (Inhalation: Gases)	Not applicable	- -	-	-	Liquid (GHS definition)
1	Acute toxicity (Inhalation: Vapours)	Classification not possible	- -	-	-	No data available.
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	No data available.
2	Skin corrosion/irritation	Not classified	- -	-	-	In a test in which 0.5 mL of undiluted this substance was applied to the skin of six rabbits for 24 hours (16CFR 1500.41 (FHSA), GLP-compliant), slight erythema and edema were seen 24 hours after the removal of patches but disappeared after seven days, the skin primary irritation index was 0.9, and it was judged as mild irritation (USEPA/HPV (2002)). Therefore, it was classified as "Not classified" in the Classification JIS (Category 3 in UN GHS classification). Besides, in humans, it is reported that after 24-hour application of 31, 80 mg of nitroglycerin to 24 volunteers, erythema was observed at application sites of almost all subjects but disappeared after several hours (Initial Risk Assessment Report Ver. 1.0, 139 (NITE, CERI, NEDO, 2008)).
3	Serious eye damage/eye irritation	Not classified	- -	-	-	In a test in which 0.1 mL of undiluted this substance was applied to the conjunctival sac of rabbits (6 animals) (16CFR 1500.42 (FHSA), GLP-compliant), the only effects in unwashed eyes were conjunctival discharges found in 2/3 animals 1 hour after the application, all eyes were normal at the other observation points, and this substance was concluded not an eye irritant (USEPA/HPV (2002)). Therefore, it was classified as "Not classified."
4	Respiratory sensitization	Classification not possible	- -	-	-	No data available.
4	Skin sensitization	Category 1	Warning	H317	P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501	It is described that this substance caused moderate sensitization by the positive rate of 40% (4/10) in a maximization test with guinea pigs and is likely to cause skin sensitization in a small fraction of humans following repeated skin contact (USEPA/HPV (2002)). Furthermore, this substance was listed as a sensitizer in Contact Dermatitis (Frosch) (Contact Dermatitis (5th, 2011), corresponding to List 1). From the above knowledge, it was classified in Category 1. Besides, in humans, a patch test in 28 volunteers, including induction procedures, resulted in no skin sensitization (Initial Risk Assessment Report Ver. 1.0, 139 (NITE, CERI, NEDO, 2008)), and there is an epidemiological survey report that a positive result was shown in a patch test to nitroglycerin in four dynamite workers with allergic contact dermatitis (Initial Risk Assessment Report Ver. 1.0, 139 (NITE, CERI, NEDO, 2008)).
5	Germ cell mutagenicity	Not classified	- -	-	-	It was classified as "Not classified" based on a negative result in a dominant lethal test by 13-week diet administration to rats (in vivo heritable germ cell mutagenicity test) (USEPA/HPV (2002)) and negative results in chromosomal aberration tests with peripheral blood lymphocytes after 5-week or 13-week diet administration to rats and chromosomal aberration tests with the bone marrow or kidney cells after 2-year diet administration to rats (all, in vivo somatic cell mutagenicity test) (USEPA/HPV (2002)). Besides, as for in vitro tests, it is reported that an Ames test was negative (Initial Risk Assessment Report Ver. 1.0, 139 (NITE, CERI, NEDO, 2008)), and a gene mutation test with Chinese hamster ovary cells was negative (USEPA/HPV (2002)).
6	Carcinogenicity	Classification not possible	- -	-	-	In a 2-year diet administration test with rats, hepatocellular carcinoma/adenoma was observed in a higher frequency in the 1.0% group (363-434 mg/kg bw/day) after 24 months (Initial Risk Assessment Report Ver. 1.0, 139 (NITE, CERI, NEDO, 2008)). And it is reported in another test that after 76-week diet administration (by 84-week-old) of 500 mg/kg/day equivalent of this substance to about 8-week-old rats, hepatocellular adenoma occurred from 32-week-old, hepatocellular carcinoma occurred from 78-week-old, incidences of hepatocellular adenoma and well-differentiated hepatocellular carcinoma were 50-75% at 84-week-old, and the occurrence of hepatocellular carcinoma was shown attributable to long-term feeding of this substance (Initial Risk Assessment Report Ver. 1.0, 139 (NITE, CERI, NEDO, 2008)). On the other hand, as for tests with mice, a slight increase in pituitary adenoma was found in females in an 18-month carcinogenicity test by drinking water administration (0, 10, 40, 330 mg/L), but no increase in tumors was seen in a 2-year feeding test (Initial Risk Assessment Report Ver. 1.0, 139 (NITE, CERI, NEDO, 2008)). From the above, tumor incidences were observed in rats, however, the 2-year diet administration test above used a small number of animals (38 per group), the other test was a special one, and tumor occurrence was not clear in mice. Therefore, based on the expert judgment, it was classified as "Classification not possible."
7	Reproductive toxicity	Category 2, Additional category: Effects on or via lactation	Warning	H361 H362	P308+P313 P201 P202 P280 P405 P501	In a three-generation reproductive test by diet administration to rats (US FDA Guidelines), a significant decrease in body weight was seen in parent animals (F0 generation) in the high dose group (concentration: 1% in the diet), all litter parameters except for sex ratios were reduced in the high dose F1a litters (the first offspring from the second generation dams), most parameters were somewhat reduced in the high dose F1b (the second offspring from the second generation dams) and F2a (the first offspring from the third generation dams), and aspermatogenesis with resulting in severe infertility occurred in F2a males (the first offspring from the third generation dams) (USEPA/HPV (2002)). Furthermore, in a developmental toxicity test by diet administration to rats during the organogenesis period (US FDA Guidelines), diaphragmatic hernias occurred only in the high dose group in which maternal animals showed lower body weights, and they were believed to be due to the test substance (USEPA/HPV (2002)). Therefore, it was classified in Category 2. And this substance is used as a coronary dilator for medical purposes, and it is described that lactation should be stopped when lactating mothers are dosed (transfer to breast milk is reported in an animal test) (Ethical Pharmaceuticals (2010)). Therefore, it was classified in the additional category: Effects on or via lactation.
8	Specific target organ toxicity - Single exposure	Category 1 (cardiovascular system, blood, nervous system)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	This substance dilates the coronary arteries and is used as a coronary dilator for medical purposes (Ethical Pharmaceuticals (2010)), and high exposure causes nausea, vomiting, a decrease in blood pressure, and depression, and sometimes confusion, delirium, methemoglobinemia, and cyanosis (Initial Risk Assessment Report Ver. 1.0, 139 (NITE, CERI, NEDO, 2008)). And it is readily absorbed through the skin and causes potent dilating effects on the arteries and veins, and by dermal exposure to this substance or exposure to the vapour, symptoms such as headache and a decrease in blood pressure occur (Japanese Journal of Industrial Health Vol. 28 No. 3 (1986)). As a case report, a 47-year-old woman intentionally ingested 24 mg of this substance and developed convulsions within 15 minutes. Cheyne-Stokes breathing (120 breaths/minute) lasted for several hours, and she had elevated systolic blood pressure and apparent tachycardia but recovered later by dosing an anticonvulsant and putting breathing device (Initial Risk Assessment Report Ver. 1.0, 139 (NITE, CERI, NEDO, 2008)). From the above, as effects of this substance in humans, vasodilation and accompanied headache, symptoms such as a decrease in blood pressure and cyanosis, methemoglobinemia, depression, delirium, confusion, etc. were observed. Therefore, it was classified in Category 1 (cardiovascular system, blood, nervous system).
9	Specific target organ toxicity - Repeated exposure	Category 1 (cardiovascular system)	Danger	H372	P260 P264 P270 P314 P501	This substance dilates the coronary arteries and is used as a coronary dilator for medical purposes (Ethical Pharmaceuticals (2010)). There are tolerance and addiction to this substance, and stopping repeated dosing increases the risk of cardiovascular disease by withdrawal responses and may cause symptoms referred to as "Monday morning angina" (Initial Risk Assessment Report Ver. 1.0, 139 (NITE, CERI, NEDO, 2008)). On the other hand, in an epidemiological survey, as a result of investigating the relationship between exposure to this substance and mortality from cardiovascular disease in male workers in munitions facilities in the United States, mortality from ischemic heart disease was related to ages and exposure, especially it was about three times higher in the high exposure group aged 45 or younger than in non-exposed controls (Initial Risk Assessment Report Ver. 1.0, 139 (NITE, CERI, NEDO, 2008)). And there are reports on sudden deaths and angina attacks in workers handling pure nitroglycerin, and increased mortality from cardiovascular/cerebrovascular disease was found in workers manufacturing dynamite that contained this substance and nitroglycol as materials in an epidemiological survey (Japanese Journal of Industrial Health Vol. 28 No. 3 (1986)). Furthermore, a Swedish report indicated a greater incidence of deaths from heart disease among former dynamite workers than in the other residents (ACGHI (7th, 2001)). Because all of the above reports showed increases in cardiovascular disorders from exposure to this substance, it was classified in Category 1 (cardiovascular system). Besides, methemoglobin formation and histological changes in the liver and kidney after repeated doses are reported in animal tests (Initial Risk Assessment Report Ver. 1.0, 139 (NITE, CERI, NEDO, 2008)), but these were not used for classification because they were findings at doses exceeding the guidance value range or slight effects.
10	Aspiration hazard	Classification not possible	- -	-	-	No data available.

ENVIRONMENTAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
11	Hazardous to the aquatic environment (Acute)	Category 1	Warning	H400	P273 P391 P501	It was classified in Category 1 from 96-hour EC50 = 0.4 mg/L for algae (Pseudokirchneriella subcapitata) (Initial Risk Assessment (NITE, CERI, NEDO, 2008)).
11	Hazardous to the aquatic environment (Long-term)	Category 1	Warning	H410	P273 P391 P501	It was classified in Category 1 due to being not rapidly degradable (BIOWIN), and 30-day NOEC = 0.03 mg/L for fish (Pimephales promelas) (Initial Risk Assessment (NITE, CERI, NEDO, 2008)).
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	This substance is not listed in the Annexes to the Montreal Protocol.

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.

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