GHS Classification Result

Chemical Name:Chlorambucil
CAS:305-03-3

Result:
ID: 21A3729
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 Not applicable - - - - The substance is an organic compound containing chlorine and oxygen (but not fluorine) which are chemically bonded only to carbon or hydrogen.
15 Organic peroxides Not applicable - - - - Organic compounds containing no bivalent -O-O- structure
16 Corrosive to metals Classification not possible - - - - Test methods applicable to solid substances are not available.

HEALTH HAZARDS
Hazard class Classification Symbol Signal word Hazard statement Precautionary statement Rationale for the classification
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)).
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 2 Warning H341: Suspected of causing 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 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)).
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 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)).
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 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)).
8 Specific target organ toxicity - Single exposure Category 1 (nervous system) Danger H370: Causes damage to organs (nervous system) 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 ...
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).
9 Specific target organ toxicity - Repeated exposure Category 1 (bone marrow, nervous system, immune system, systemic toxicity) Danger H372: Cause damage to organs through prolonged or repeated exposure (bone marrow, nervous system, immune system, systemic toxicity) 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.
P314: Get medical advice/attention if you feel unwell.
P501: Dispose of contents/container to ...
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).
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)


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