GHS Classification Result

Chemical Name：Busulfan
CAS：55-98-1

Result：
ID: 21A3728
Classifier: Ministry of Health, Labour and Welfare （MHLW）, Ministry of the Environment （MOE）
Year Classified: FY2009
Reference Manual: GHS Classification Guidance by the Japanese Government （March, 2009）

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 - - - - Solid (GHS definition)
3 Aerosols Not applicable - - - - Not aerosol products.
4 Oxidizing gases Not applicable - - - - Solid (GHS definition)
5 Gases under pressure Not applicable - - - - Solid (GHS definition)
6 Flammable liquids Not applicable - - - - Solid (GHS definition)
7 Flammable solids Classification not possible - - - - No data available.
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 applicable - - - - Solid (GHS definition)
10 Pyrophoric solids Classification not possible - - - - No data available.
11 Self-heating substances and mixtures Classification not possible - - - - Test methods applicable to solid (melting point <= 140 degC) 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 - - - - Solid (GHS definition)
14 Oxidizing solids Classification not possible - - - - No data available.
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 3 Danger H301: Toxic if swallowed P301+P310: IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P264: Wash ... thoroughly after handling.
P270: Do not eat, drink or smoke when using this product.
P321: Specific treatment （see ... on this label）.
P330: Rinse mouth.
P405: Store locked up.
P501: Dispose of contents/container to ... 		Based on a LD50 value of 120 mg/kg for mice (HSDB (2009)), the substance was classified into Category 3.
1 Acute toxicity （Dermal） Classification not possible - - - - No data available.
1 Acute toxicity （Inhalation: Gases） Not applicable - - - - Solid (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 Classification not possible - - - - No data available.
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 data available.
5 Germ cell mutagenicity Category 1B Danger H340: May cause genetic defects 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 ... 		Based on a positive result in a rodent dominant lethal test (in vivo heritable germ cell mutagenicity test) (IARC suppl. 7 (1987)) and positive results in rodent bone marrow cell chromosomal aberration test and micronucleus test (in vivo somatic cell mutagenicity tests) (IARC suppl. 7 (1987)), the substance was classified into Category 1B. As relevant information, from in vitro mutagenicity tests, there are reports of a positive Ames test (NTP DB (access on Oct. 2009)) and human and rodent cell chromosomal aberration tests (IARC suppl. 7 (1987)).
6 Carcinogenicity Category 1A Danger H350: May cause cancer 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 ... 		Based on the classification of "Group 1" in IARC (IARC 100 (2008)), the substance was classified into Category 1A. Several reports described dysplasias and atypical cell formation among leukemia patients who have received treatment and a few cases of cancer were reported. Among animal tests, it was reported that administration to rats by oral or to mice by intraperitoneal injection did not significantly increase the incidence of tumors but intravenous administration to mice significantly increased the incidence of thymic lymphomas and ovarian tumours (IARC vol. 4 (1974)).
7 Reproductive toxicity Category 1A Danger H360: May damage 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 ... 		There is a case report that treatment of a pre-adolescent girl with the substance prevented the onset of puberty due to ovarian failure (HSDB (2009)). Examination of 21 girls, aged 11 - 21 years, who had earlier received several years of high-dose chemotherapy and autologous bone marrow transplantation, demonstrated that the 10 girls who received the substance all developed severe and persistent ovarian failure (HSDB (2009)). A woman treated with the substance throughout the majority of her pregnancy gave birth to an infant with severe growth retardation, cleft palate, microphthalmia and hypoplastic ovaries. It was concluded that these malformations were caused by the substance (Birth Defects (3rd, 2000)). A case of myeloschisis in a six week old human embryo was reported for a mother treated with the substance before and during the early stages of gestation for leukemia (Birth Defects (3rd, 2000)). Additionally, there is a report of a infant with multiple malformations whose mother was treated with the substance for lukemia during gestation (Birth Defects (3rd, 2000)). The substance is classified into Category D (There is positive evidence of human fetal risk, but potential benefits may warrant use of the drug in pregnant women despite potential risks) from FDA (The Merck Manual (18th, Japanese)). Based on all this information, the substance corresponds to a known human reproductive toxicant and is classified into Category 1A. From animal tests, there is a report that microencephaly and microphthalmia were observed in the embryos/fetuses from rats exposed intraperitoneally during gestation (HSDB (2009)) and a report that the substance is teratogenic in mice, rats and rabbits (EMEA (2005)).
8 Specific target organ toxicity - Single exposure Category 2 (blood system, nervous system, lung, liver) Warning H371: May cause damage to organs (blood system, nervous system, lung, liver) P309+P311: IF exposed or if you feel unwell: 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.
P405: Store locked up.
P501: Dispose of contents/container to ... 		Based on a report that the major adverse effect of the substance is hematologic toxicity and causes myelosuppression manifested as leukopenia, thrombocytopenia, anemia, or any combination of these (HSDB (2009)), the blood system was regarded as a target organ. Based on reports that seizures were reported in patients receiving the substance orally, including administration at high doses as part of a conditioning regimen prior to bone marrow transplantation (HSDB (2009)) and that two patients without prior histories of neurologic disorders experienced generalized seizures while receiving high-doses of the substance as part of a preparative regimen for allogeneic bone marrow transplantation (HSDB (2009)), the nervous system was regarded as a target organ. Since interstitial pneumonitis and pulmonary fibrosis have also been reported in patients receiving high oral doses as a component of a conditioning regimen prior to allogeneic bone marrow transplantation (HSDB (2009)) and nonspecific interstitial fibrosis was diagnosed by lung biopsy in one patient receiving IV administration who subsequently died from respiratory failure (HSDB (2009)), the lung was regarded as a target organ. Additionally, hyperbilirubinemia was reported in patients receiving oral or IV administration of the substance as a component of a conditioning regimen prior to allogeneic hematopoietic stem cell transplant. Since the substance was associated with hepatic veno-occlusive disease in some patients and jaundice, hepatomegaly and increases in serum ALT were reported (HSDB (2009)), the liver was regarded as a target organ. Since these information are reported in a document in List 2, the substance was classified into Category 2 (blood system, nervous system, lung, liver). From animal tests, there are signs of stimulation of the central nervous system with convulsions in mice following a one-time exposure (HSDB (2009)).
9 Specific target organ toxicity - Repeated exposure Category 2 (blood system, lung, eye, skin, systemic toxicity) Warning H373: May cause damage to organs through prolonged or repeated exposure (blood system, lung, eye, skin, systemic toxicity) P260: Do not breathe dust/fume/gas/mist/vapours/spray.
P314: Get medical advice/attention if you feel unwell.
P501: Dispose of contents/container to ... 		Based on a report that the major adverse effect of the substance is hematologic toxicity and causes myelosuppression manifested as leukopenia, thrombocytopenia, anemia, or any combination of these (HSDB (2009)) and a report that the substance can suppress hemopoiesis resulting in aplastic anemia (DHP (13th, 2002)), the blood system is regarded as a target organ. From a report that a rare, but serious syndrome which occurs only after long-term therapy (4 months to 10 years) is manifested by bronchopulmonary dysplasia with a diffuse interstitial pulmonary fibrosis and is characterized by persistent cough, fever, rales, and dyspnea (HSDB (2009)), the lung is regarded as a target organ. Since corneal thinning and lens changes also were reported in patients receiving oral administration (HSDB (2009)) and the occurrence of cataract was reported after long-term administration (HSDB (2009)), the eye is also regarded as a target organ. Since hyperpigmentation was reported in 5 - 10% of patients receiving oral administration and erythema nodosum, erythema multiforme, urticaria, porphyria cutanea tarda, and dryness of the skin also were reported in patients treated orally (HSDB (2009)), the skin is regarded as a target organ. Additionally, since infections including sepsis and pneumonia were reported in patients receiving the substance and wasting or Addison-like syndrome has occurred in a small number of patients after long-term therapy (HSDB (2009)), systemic toxicity is also an adverse effect. Since these information are reported in a document in List 2, the substance was classified into Category 2 (blood system, lung, eye, skin, systemic toxicity).
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）

To GHS Information