Chemical Name：Mixture of isosorbide dinitrate (which contains more than 60%wt of lactose, mannose, starch or calcium hydrogen phosphate)
CAS：87-33-2

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 ...	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.
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.
1	Acute toxicity （Inhalation: Gases）	Not applicable	-	-	-	-	Solid
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	-	-	-	-	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.
3	Serious eye damage/eye irritation	Classification not possible	-	-	-	-	No data available.
4	Respiratory sensitization	Classification not possible	-	-	-	-	No data available.
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.
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.
6	Carcinogenicity	Classification not possible	-	-	-	-	No data available.
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 ...	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.
8	Specific target organ toxicity - Single exposure	Category 1 (circulatory system, central nervous system, gastrointestinal tract, liver, blood)		Danger	H370: Causes damage to organs (circulatory system, central nervous system, gastrointestinal tract, liver, blood)	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 ...	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.
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.
10	Aspiration hazard	Classification not possible	-	-	-	-	No data available.