NITE - Chemical Management Field

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

GENERAL INFORMATION

Item	Information
CAS RN	87-33-2
Chemical Name	Mixture of isosorbide dinitrate (which contains more than 60%wt of lactose, mannose, starch or calcium hydrogen phosphate)
Substance ID	m-nite-87-33-2_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)	To Workplace Safety Site (MHLW)
Sample SDS by MHLW (External link)	To Workplace Safety Site (MHLW)
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	Classification not possible	- -	-	-	The substance of pure form is reported to possess explosive properties under dry conditions (Bretherick). However, the substance is used primarily as cardiotonic drugs, which have no information available on explosive properties evaluations. Thus, the substance was classified into the "Classification not possible" category.	FY2007	GHS Classification Manual （10 Feb, 2006）/Technical Guidance Document on the GHS Classification （6 Dec, 2005）
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2007	GHS Classification Manual （10 Feb, 2006）/Technical Guidance Document on the GHS Classification （6 Dec, 2005）
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.	FY2007	GHS Classification Manual （10 Feb, 2006）/Technical Guidance Document on the GHS Classification （6 Dec, 2005）
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2007	GHS Classification Manual （10 Feb, 2006）/Technical Guidance Document on the GHS Classification （6 Dec, 2005）
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2007	GHS Classification Manual （10 Feb, 2006）/Technical Guidance Document on the GHS Classification （6 Dec, 2005）
6	Flammable liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2007	GHS Classification Manual （10 Feb, 2006）/Technical Guidance Document on the GHS Classification （6 Dec, 2005）
7	Flammable solids	Classification not possible	- -	-	-	Since no test results on the substance of pure form are available, it was classified into the "Classification not possible" category. (The substance mixed with 60% or more lactose, mannose, starch, or calcium hydrogen phosphate is defined as UN 2907, Division 4.1, packing group II. These products are classified into Category 1.)	FY2007	GHS Classification Manual （10 Feb, 2006）/Technical Guidance Document on the GHS Classification （6 Dec, 2005）
8	Self-reactive substances and mixtures	Classification not possible	- -	-	-	It is documented that the substance is impact and friction sensitive, and shows sensitivity to initiation to detonation by std no. 6 and no. 8 strength detonators (HSDB (2005)). Though the substance is apparently self-reactive hazardous material, it was classified into the "Classification not possible" category based on GHS definition.	FY2007	GHS Classification Manual （10 Feb, 2006）/Technical Guidance Document on the GHS Classification （6 Dec, 2005）
9	Pyrophoric liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2007	GHS Classification Manual （10 Feb, 2006）/Technical Guidance Document on the GHS Classification （6 Dec, 2005）
10	Pyrophoric solids	Classification not possible	- -	-	-	No data available.	FY2007	GHS Classification Manual （10 Feb, 2006）/Technical Guidance Document on the GHS Classification （6 Dec, 2005）
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	No data available.	FY2007	GHS Classification Manual （10 Feb, 2006）/Technical Guidance Document on the GHS Classification （6 Dec, 2005）
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).	FY2007	GHS Classification Manual （10 Feb, 2006）/Technical Guidance Document on the GHS Classification （6 Dec, 2005）
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2007	GHS Classification Manual （10 Feb, 2006）/Technical Guidance Document on the GHS Classification （6 Dec, 2005）
14	Oxidizing solids	Classification not possible	- -	-	-	No data available.	FY2007	GHS Classification Manual （10 Feb, 2006）/Technical Guidance Document on the GHS Classification （6 Dec, 2005）
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Containing no bivalent -O-O- structure in the molecule	FY2007	GHS Classification Manual （10 Feb, 2006）/Technical Guidance Document on the GHS Classification （6 Dec, 2005）
16	Corrosive to metals	Classification not possible	- -	-	-	No data available.	FY2007	GHS Classification Manual （10 Feb, 2006）/Technical Guidance Document on the GHS Classification （6 Dec, 2005）
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	No test results on the substance are available. In a test on isosorbide dinitrate, rat LD50 was 747 mg/kg (RTECS, accessed in August 2007), and in a test on lactose, rat LD50 was > 10000 mg/kg, indicating that these ingredients are presumed not acutely toxic. Thus, in accordance with GHS classification criteria (GHS-2003, 3.1.3.6: classification of mixtures based on ingredients of the mixture (additivity formula)), this substance was classified into Category 4, ignoring ingredients and based on the LD50 value of isosorbide dinitrate.	FY2007	GHS Classification Manual （10 Feb, 2006）/Technical Guidance Document on the GHS Classification （6 Dec, 2005）
1	Acute toxicity (Dermal)	Not classified	- -	-	-	No test results on the substance are available. In a test on isosorbide dinitrate, rat LD50 was > 3000 mg/kg (RTECS, accessed in August 2007). In addition, all ingredients such as lactose are presumed not acutely toxic. Thus, in accordance with GHS classification criteria (GHS-2003, 3.1.3.6: classification of mixtures based on ingredients of the mixture (additivity formula)), the substance was classified into the "Not classified" category, ignoring ingredients and based on the LD50 value of isosorbide dinitrate.	FY2007	GHS Classification Manual （10 Feb, 2006）/Technical Guidance Document on the GHS Classification （6 Dec, 2005）
1	Acute toxicity (Inhalation: Gases)	Not classified (Not applicable)	- -	-	-	Solid	FY2007	GHS Classification Manual （10 Feb, 2006）/Technical Guidance Document on the GHS Classification （6 Dec, 2005）
1	Acute toxicity (Inhalation: Vapours)	Classification not possible	- -	-	-	No data available.	FY2007	GHS Classification Manual （10 Feb, 2006）/Technical Guidance Document on the GHS Classification （6 Dec, 2005）
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	No data available.	FY2007	GHS Classification Manual （10 Feb, 2006）/Technical Guidance Document on the GHS Classification （6 Dec, 2005）
2	Skin corrosion/irritation	Not classified	- -	-	-	No test results on the substance are available. In a rabbit skin irritation test in which isosorbide dinitrate was applied, mild irritation was noted after a 24-hour exposure (RTECS, accessed in August 2007). Based on this report, we determined that up to 4-hour exposure to a mixture containing less than 40% isosorbide dinitrate may cause very mild irritation and classified this mixture into the "Not classified" category. As additional background information, in a clinical study in which isosorbide dinitrate was dermally applied using patches, skin irritation and primary irritant contact dermatitis were noted in more than 5% of the subjects. However, whether isosorbide dinitrate is responsible for the irritation is unclear.	FY2007	GHS Classification Manual （10 Feb, 2006）/Technical Guidance Document on the GHS Classification （6 Dec, 2005）
3	Serious eye damage/eye irritation	Classification not possible	- -	-	-	No data available.	FY2007	GHS Classification Manual （10 Feb, 2006）/Technical Guidance Document on the GHS Classification （6 Dec, 2005）
4	Respiratory sensitization	Classification not possible	- -	-	-	No data available.	FY2007	GHS Classification Manual （10 Feb, 2006）/Technical Guidance Document on the GHS Classification （6 Dec, 2005）
4	Skin sensitization	Classification not possible	- -	-	-	No test results on this substance are available. In a clinical study in which isosorbide dinitrate was dermally applied using patches, skin irritation and allergic contact dermatitis were noted in more than 5% of the subjects to whom isosorbide dinitrate were applied. However, since whether isosorbide dinitrate is responsible for the irritation is unclear, classification is not possible.	FY2007	GHS Classification Manual （10 Feb, 2006）/Technical Guidance Document on the GHS Classification （6 Dec, 2005）
5	Germ cell mutagenicity	Not classified	- -	-	-	No test results are available on this substance. Regarding isosorbide dinitrate, negative results were obtained in an Ames test, mutation test using cultured mouse lymphoma cells, chromosomal aberration test using human lymphocytes, and in vivo mouse micronucleus test (HSDB (2005)). Based on these negative results, isosorbide dinitrate was classified into the "Not classified" category. In addition, the whole mixture was also classified into the "Not classified" category by expert judgement since other ingredients are not mutagenic as well.	FY2007	GHS Classification Manual （10 Feb, 2006）/Technical Guidance Document on the GHS Classification （6 Dec, 2005）
6	Carcinogenicity	Classification not possible	- -	-	-	No data available.	FY2007	GHS Classification Manual （10 Feb, 2006）/Technical Guidance Document on the GHS Classification （6 Dec, 2005）
7	Reproductive toxicity	Category 2	Warning	H361	P308+P313 P201 P202 P280 P405 P501	No test results are available on this substance. Regarding isosorbide dinitrate, no effects of the compound at 25 or 100 mg/kg/day were noted in a two-litter reproduction study (HSDB (2005)). However, studies (probably conducted during the organogenetic period, though not clearly indicated in the HSDB document) in rabbits given isosorbide dinitrate in oral doses of 35 and 150 times the maximum daily recommended human doses have shown a dose-related increase in embryotoxicity. Since these results suggest that the substance also may be associated with embryotoxicity similar to that associated with isosorbide dinitrate, it was classified into Category 2.	FY2007	GHS Classification Manual （10 Feb, 2006）/Technical Guidance Document on the GHS Classification （6 Dec, 2005）
8	Specific target organ toxicity - Single exposure	Category 1 (circulatory organ, central nervous system, gastrointestinal tract, liver, blood)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	No test results are available on this substance. Since isosorbide dinitrate has vasodilation effects (selective to the veins), it is clinically used to dilate the coronary arteries in the cases of acute cardiac failure or unstable angina pectoris. Regarding the pharmaceutical preparation of isosorbide dinitrate (sublingual tablets, oral agents (timed-release tablets and timed-release capsules), intra-oral spray, and intravenous drip), the following side effects are listed: more than 5% of the subjects suffered from headaches (sublingual tablets), 0.1-5% of the subjects suffered from neuropsychiatric symptoms such as a heavy-headed sensation and weakness, cardiovascular symptoms such as decreased blood pressure, dizziness/lightheadedness, flushing, heat sensation, edemas, palpitation, decreased cardiac output, and loss of consciousness, digestive symptoms such as nausea/vomiting, stomach discomfort, loss of appetite, and abdominal pain, effects to the liver such as elevated GOT/GPT in the blood, and effects to the blood such as decreased arterial oxygen pressure, and unknown percentages of the subjects suffered from discomfort, rashes, and methemoglobinemia (2007 Drugs in Japan, 1078-1083, Jiho (2007); The Japanese pharmacopoeia 14th edition, official monographs, C-1643-1647, Hirokawa Bookstore (2001)). In addition, overdoses of isosorbide dinitrate affect the heart and blood vessels causing hypotension, tachycardia, headache, drowsiness, fever, nausea, and other symptoms (HSDB (2005)). In light of these studies, isosorbide dinitrate was found to affect the cardiovascular system, central nervous system, gastrointestinal tracts, liver, and blood, and this substance is presumed to have similar effects. Thus, this substance was classified into Category 1 for its toxic effects on the cardiovascular system, central nervous system, gastrointestinal tract, liver, and blood.	FY2007	GHS Classification Manual （10 Feb, 2006）/Technical Guidance Document on the GHS Classification （6 Dec, 2005）
9	Specific target organ toxicity - Repeated exposure	Classification not possible	- -	-	-	No test results are available on this substance or on the toxicity of isosorbide dinitrate in repeated administration tests. However, in clinical applications of isosorbide dinitrate, its efficacy and side effects such as headache and hypotension receded as greater tolerance developed than did in repeated administration tests (Drugs in Japan, 1078-1083, Jiho (2007); HSDB, 2005). In light of these reports, both repeated and single administrations presumably induce similar side effects, and it is likely the same with the substance. However, due to lack of test results on the substance, it was classified into the "Classification not possible" category.	FY2007	GHS Classification Manual （10 Feb, 2006）/Technical Guidance Document on the GHS Classification （6 Dec, 2005）
10	Aspiration hazard	Classification not possible	- -	-	-	No data available.	FY2007	GHS Classification Manual （10 Feb, 2006）/Technical Guidance Document on the GHS Classification （6 Dec, 2005）

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.	FY2007	GHS Classification Manual （10 Feb, 2006）/Technical Guidance Document on the GHS Classification （6 Dec, 2005）
11	Hazardous to the aquatic environment Long term (Chronic)	Classification not possible	- -	-	-	No data available.	FY2007	GHS Classification Manual （10 Feb, 2006）/Technical Guidance Document on the GHS Classification （6 Dec, 2005）
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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