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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	81103-11-9
Chemical Name	Clarithromycin
Substance ID	R01-A-026
Classification year (FY)	FY2019
Ministry who conducted the classification	Ministry of Health, Labour and Welfare (MHLW)/Ministry of the Environment (MOE)
New/Revised	New
Classification result in other fiscal year
Download of Excel format	Excel file

REFERENCE INFORMATION

Item	Information
Guidance used for the classification (External link)	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
UN GHS document (External link)	UN GHS document
Definitions/Abbreviations (Excel file)	Definitions/Abbreviations
Model Label by MHLW (External link)
Model SDS by MHLW (External link)
OECD/eChemPortal (External link)	eChemPortal

PHYSICAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Explosives	*	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule. It was classified as "Not classified (Not applicable)."
2	Flammable gases	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
3	Aerosols	*	- -	-	-	Not aerosol products. It was classified as "Not classified (Not applicable)."
4	Oxidizing gases	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
5	Gases under pressure	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
6	Flammable liquids	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
7	Flammable solids	*	- -	-	-	No data available.
8	Self-reactive substances and mixtures	*	- -	-	-	There are no chemical groups associated with explosive or self-reactive properties present in the molecule. It was classified as "Not classified (Not applicable)."
9	Pyrophoric liquids	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
10	Pyrophoric solids	*	- -	-	-	No data available.
11	Self-heating substances and mixtures	*	- -	-	-	No data available.
12	Substances and mixtures which, in contact with water, emit flammable gases	*	- -	-	-	The chemical structure of the substance does not contain metals or metalloids (B, Si, P, Ge, As, Se, Sn, Sb, Te, Bi, Po, At). It was classified as "Not classified (Not applicable)."
13	Oxidizing liquids	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
14	Oxidizing solids	*	- -	-	-	The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is chemically bonded only to carbon or hydrogen. It was classified as "Not classified (Not applicable)."
15	Organic peroxides	*	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule. It was classified as "Not classified (Not applicable)."
16	Corrosive to metals	*	- -	-	-	Classification is not possible because test methods applicable to solid substances are not available.
17	Desensitized explosives	*	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule. It was classified as "Not classified."

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Acute toxicity (Oral)	Category 4	Warning	H302	P301+P312 P264 P270 P330 P501	[Rationale for the Classification] Based on (1), it was classified in Category 4. [Evidence Data] (1) LD50 for rats: 1,270 mg/kg (HSDB (Access on October 2019)) [Reference Data, etc.] (2) LD50 for rats: male: 3,470 mg/kg, female: 2,700 mg/kg (Pharmaceutical Interview Forms (clarithromycin preparation (April, 2019 (23rd edition))))
1	Acute toxicity (Dermal)	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
1	Acute toxicity (Inhalation: Gases)	*	- -	-	-	[Rationale for the Classification] Solid (GHS definition). It was classified as "Not classified (Not applicable)."
1	Acute toxicity (Inhalation: Vapours)	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
1	Acute toxicity (Inhalation: Dusts and mists)	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
2	Skin corrosion/irritation	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
3	Serious eye damage/eye irritation	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Respiratory sensitization	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
5	Germ cell mutagenicity	*	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) As for in vivo, there was a report of a negative result in a micronucleus test with mouse bone marrow cells (Pharmaceutical Interview Forms (clarithromycin preparation (April, 2019 (23rd edition)))). (2) As for in vitro, there were reports of negative results in a bacterial reverse mutation test, a micronucleus test and a chromosomal aberration test with cultured mammalian cells (NTP DB (Access on September 2019), HSDB (Access on September 2019), Pharmaceutical Interview Forms (April, 2019 (23rd edition))).
6	Carcinogenicity	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
7	Reproductive toxicity	Category 2, Additional category: Effects on or via lactation	Warning	H361 H362	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1)-(3), it was classified in Category 2. In addition, based on (4), "additional category for effects on or via lactation" was added to the classification. [Evidence Data] (1) In a teratogenicity test with rats by the oral route, cardiovascular anomalies were observed in the fetuses at the highest dose where maternal toxicity (unknown details) was observed (Pharmaceutical Interview Forms (April, 2019 (23rd edition)), HSDB (Access on September 2019)). (2) In a teratogenicity test with mice by the oral route, cleft palate was observed in the fetuses at the highest dose where maternal toxicity (unknown details) was observed (Pharmaceutical Interview Forms (April, 2019 (23rd edition)), HSDB (Access on September 2019)). (3) It is described that in animal experiments, since fetotoxicities (abnormalities in the cardiovascular system, cleft palate, growth retardation, etc.) were reported at the high doses where toxicity was manifested in maternal animals, it should be administered to pregnant women or women who may be pregnant only when the benefit exceeds the risk (Ethical Pharmaceuticals 2017 (2016)). (4) Since it is reported that this substance will pass into breast milk, nursing women should avoid breast feeding during treatment. Besides, there is a description that concentrations in milk in an animal experiment (rats) remained about 2.5 times higher than those in the blood (Ethical Pharmaceuticals 2017 (2016)).
8	Specific target organ toxicity - Single exposure	Category 1 (gastrointestinal tract, liver)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	[Rationale for the Classification] This substance is a macrolide antibiotic drug, and it is pharmaceutically used for the treatment of various bacterial infections by oral administration. Based on (1), it was classified in Category 1 (gastrointestinal tract, liver). The increase in eosinophil was not adopted as evidence since there is a possibility of changes due to hypersensitivity, etc. [Evidence Data] (1) Although the number of doses was unknown, as major side effects, symptoms of the blood system (increased eosinophil count), liver (elevated AST and ALT) and gastrointestinal tract (nausea, vomiting, gastric discomfort, abdominal distension, abdominal pain, diarrhea) were observed at frequencies of 0.1 to <5% (Ethical Pharmaceuticals 2017 (2016)). [Reference Data, etc.] (2) As for serious side effects (frequencies unknown for all), there are reports of QT prolongation, ventricular tachycardia (including Torsades de pointes) or ventricular fibrillation, fulminant hepatitis, liver dysfunction, jaundice or hepatic failure, decreases in platelets and pancytopenia, hemolytic anemia, leukopenia or agranulocytosis, PIE syndrome, interstitial pneumonia, pseudomembranous colitis or hemorrhagic colitis, rhabdomyolysis, convulsions, and acute nephropathy or tubulointerstitial nephritis (Ethical Pharmaceuticals 2017 (2016)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (gastrointestinal tract, liver)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1), the main side effects by repeated administration of this formulation were observed in the gastrointestinal tract and liver. Therefore, it was classified in Category 1 (gastrointestinal tract, liver). As for the increased eosinophils, it was not adopted as evidence due to possible changes due to hypersensitivity, etc. [Evidence Data] (1) As for information on side effects for patients with general infectious diseases, out of a total of 3,894 cases (2,885 for adults and 1,009 for children) at the time of approval, side effects were observed in 96 cases for adults (3.33%) and 21 cases for children (2.08%), and 117 cases for a total (3.00%). The main types of side effects were gastrointestinal symptoms such as abdominal pain and diarrhea. There is a report that increased ALT and AST, and increased eosinophil count were the main changes in laboratory values (Ethical Pharmaceuticals 2017 (2016)). [Reference Data, etc.] (3) As for serious side effects (frequencies unknown for all), there are reports of QT prolongation, ventricular tachycardia (including Torsades de pointes) or ventricular fibrillation, fulminant hepatitis, liver dysfunction, jaundice or hepatic failure, decreases in platelet, pancytopenia and hemolytic anemia, leukopenia or agranulocytosis, PIE syndrome, interstitial pneumonia, pseudomembranous colitis or hemorrhagic colitis, rhabdomyolysis, convulsions, and acute nephropathy or tubulointerstitial nephritis (Ethical Pharmaceuticals 2017 (2016)).
10	Aspiration hazard	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.

ENVIRONMENTAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
11	Hazardous to the aquatic environment Short term (Acute)	Category 1	Warning	H400	P273 P391 P501	It was classified in Category 1 from 72-hour ErC50 = 0.0069 mg/L for algae (Pseudokirchneriella subcapitata) (Environmental Risk Assessment for Chemical Substances Vol. 16 (Ministry of the Environment, 2018)).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 1	Warning	H410	P273 P391 P501	If chronic toxicity data are used, then it is classified in Category 1 due to being not rapidly degradable (BIOWIN), and 72-hour NOEC = 0.00245 mg/L for algae (Pseudokirchneriella subcapitata) (Environmental Risk Assessment for Chemical Substances Vol. 16 (Ministry of the Environment, 2018)). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained, then it is classified as "Not classified" due to being not rapidly degradable (BIOWIN), 96-hour LC50 > 100 mg/L for fish (Oryzias latipes) (Environmental Risk Assessment for Chemical Substances Vol. 16 (Ministry of the Environment, 2018)). By drawing a comparison between the above results, it was classified in Category 1.
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	Classification not possible due to lack of data.

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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