NITE - Chemical Management Field

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

GENERAL INFORMATION

Item	Information
CAS RN	55-98-1
Chemical Name	Busulfan
Substance ID	m-nite-55-98-1_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.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
6	Flammable liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
7	Flammable solids	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
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.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
9	Pyrophoric liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
10	Pyrophoric solids	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Test methods applicable to solid (melting point <= 140 degC) substances are not available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
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).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
14	Oxidizing solids	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Organic compounds containing no bivalent -O-O- structure	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
16	Corrosive to metals	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
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 3	Danger	H301	P301+P310 P264 P270 P321 P330 P405 P501	Based on a LD50 value of 120 mg/kg for mice (HSDB (2009)), the substance was classified into Category 3.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
1	Acute toxicity (Dermal)	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
1	Acute toxicity (Inhalation: Gases)	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
1	Acute toxicity (Inhalation: Vapours)	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
2	Skin corrosion/irritation	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
3	Serious eye damage/eye irritation	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
4	Respiratory sensitization	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
4	Skin sensitization	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
5	Germ cell mutagenicity	Category 1B	Danger	H340	P308+P313 P201 P202 P280 P405 P501	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)).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
6	Carcinogenicity	Category 1A	Danger	H350	P308+P313 P201 P202 P280 P405 P501	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)).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
7	Reproductive toxicity	Category 1A	Danger	H360	P308+P313 P201 P202 P280 P405 P501	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)).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
8	Specific target organ toxicity - Single exposure	Category 2 (blood system, nervous system, lung, liver)	Warning	H371	P308+P311 P260 P264 P270 P405 P501	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)).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
9	Specific target organ toxicity - Repeated exposure	Category 2 (blood system, lung, eye, skin, systemic)	Warning	H373	P260 P314 P501	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).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
10	Aspiration hazard	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）

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.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
11	Hazardous to the aquatic environment Long term (Chronic)	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
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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