NITE - Chemical Management Field

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

GENERAL INFORMATION

Item	Information
CAS RN	305-03-3
Chemical Name	Chlorambucil
Substance ID	m-nite-305-03-3_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	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	Not classified (Not applicable)	- -	-	-	The substance is an organic compound containing chlorine and oxygen (but not fluorine) which are chemically bonded only to carbon or hydrogen.	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	- -	-	-	Test methods applicable to solid substances are not 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)	Classification not possible	- -	-	-	Classification not possible due to lack of data. As relevant information, a LD50 value is 76 mg/kg for rats (RTECS (2009)).	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 2	Warning	H341	P308+P313 P201 P202 P280 P405 P501	Based on positive results in bone marrow and peripheral blood micronucleus tests by intraperitoneal injection to mice (NTP DB (access on Oct. 2009)) and embryo chromosomal aberration test by intraperitoneal injection to pregnant rats (IARC vol. 26 (1981)) (in vivo somatic cell mutagenicity tests), the substance was classified into Category 2. As relevant information, from in vitro mutagenicity tests, there are reports of a positive Ames test and a positive human peripheral lymphocytes chromosomal aberration test (IARC vol. 26 (1981), NTP DB (access on Oct. 2009)).	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 vol. 100A (2008)), the substance was classified into Category 1A. Many cases of leukaemia (mainly acute non-lymphocytic leukaemia) were reported following therapy by the substance for non-malignant diseases (mainly rheumatoid arthritis, collagen diseases, glomerulonephritis) and malignant diseases (mostly Hodgkin's disease, non-Hodgkin's lymphoma, chronic lymphocytic leukaemia) (IARC 26 (1981). Among animal tests, it was reported that increased incidence of lung tumour were observed at 39 weeks in a mouse test by intraperitoneal injection for 4 weeks (IARC 26 (1981)).	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 are the following evidence of human reproductive toxicity: Oligospermia, azoospermia and disappearance of testicular germinal cells were observed dose-dependently in male patients treated with the substance (IARC 26 (1981)). A woman who became pregnant while receiving the substance and continued to receive it for another 2.5 months, had a therapeutic abortion at 3.5 months and the fetus had no left kidney or ureter (IARC 26 (1981)). Retinal coloboma was observed in a fetus whose mother was treated with the substance between the 3th and 4th months of pregnancy (Birth Defects (3rd, 2000)). A female infant died from severe cardiovascular malformation 3 days after normal birth. The mother was prescribed the substance and steroid at week 10 of pregnancy for the treatment of scleroderma (Birth Defects (3rd, 2000)). Additionally, the following animal tests show clear evidences of reproductive toxicity, especially teratogenicity: Repeated i.p. injections resulted in testicular atrophy and decreased spermatogenic activity in mice (IARC vol. 26 (1981) Urogenital malformations, including absence of a kidney, were found in fetuses of rats. This substance was strongly teratogenic (HSDB 2003)); Microcephaly occurred in fetuses from mice orally administered the substance and severe cranial malformations, identified as cranioschisis or encephalocele were often observed (HSDB (2003)). Based on all information, the substance corresponds to a known human reproductive toxicant and was classified into Category 1A. As relevant information, it is not known whether the substance passes into breast milk (PHYSICIANS' DESK REFERENCE (2010)).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
8	Specific target organ toxicity - Single exposure	Category 1 (nervous system)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	Convulsions were reported in 10 children treated with chlorambucil, 2 of whom accidentally received very large amounts (IARC 26 (1981)). There is a report that a major symptom in 2 children accidentally exposed was CNS excitability and symptoms after a dose of 5 mg/kg were convulsion and coma (DHP (13th, 2002)). Additionally, it was reported that a dose of approximately 1.5 mg/kg produced vomiting, ataxia and jerky movements (HSDB (2003)). Based on all information, the substance was classified into Category 1 (nervous system).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
9	Specific target organ toxicity - Repeated exposure	Category 1 (bone marrow, nervous system, immune system, systemic)	Danger	H372	P260 P264 P270 P314 P501	Based on a report that myelosuppression was observed in 2/3 of 495 patients treated with the substance for rheumatoid arthritis (IARC 26 (1981)), the substance was classified into Category 1 (bone marrow). Since convulsions were reported in 10 children treated, two of whom accidentally received very large amounts (IARC 26 (1981)), the substance was classified into Category 1 (nervous system). Infections (attributed to immunosuppression) were observed in about 30% of patients treated with the substance for rheumatoid arthritis (IARC 26 (1981)). The substance caused keratitis epithelialis in association with exfoliative dermatitis in one patient under treatment for lymphosarcoma (HSDB (2003)). Rash or dermatitis including maculopapular and urticarial, or occurrence or exacerbation of herpes zoster may occur in patients receiving the substance, and reactions including rash progressing to erythema multiforme, toxic epidermal necrolysis, and Stevens-Johnson syndrome were reported (rarely) (HSDB (2003)). Additionally, a case of interstitial lung disease which regressed on discontinuation of the drug but recurred on resumption of treatment was reported (IARC 26 (1981)). Based on all information, the substance was classified into Category 1 (immune system, 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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