NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	80214-83-1
Chemical Name	Roxithromycin
Substance ID	R01-A-028
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	*	- -	-	-	It was classified as "Not classified" because it is estimated that it does not ignite at normal temperatures from information that it is stable to temperatures, humidity, and light (Pharmaceutical Interview Forms (Roxithromycin 150 mg tablets (Revised 2018))).
11	Self-heating substances and mixtures	*	- -	-	-	It was classified as "Not classified" because it is estimated that it does not ignite at normal temperatures from information that it is stable to temperatures, humidity, and light (Pharmaceutical Interview Forms (Roxithromycin 150 mg tablets (Revised 2018))).
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 to the element other than carbon or hydrogen (N). However, the classification is not possible due to no data.
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: male: 1,059 mg/kg, female: 1,712 mg/kg (Pharmaceutical Interview Forms (Roxithromycin 150 mg tablets (Revised 2018))).
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] Although there is a description in (1), it was classified as "Classification not possible" due to lack of data. [Reference Data, etc.] (1) No antigenicity was observed in a delayed skin reaction (guinea pigs) (Pharmaceutical Interview Forms (Roxithromycin 150 mg tablets (Revised 2018))).
5	Germ cell mutagenicity	*	- -	-	-	[Rationale for the Classification] Based on (1) and (2), since the results of all standard combination tests, including in vivo and in vitro tests, were negative, it was classified as "Not classified." [Evidence Data] (1) As for in vivo, there is a report on a negative result in a micronucleus test with mice (Pharmaceutical Interview Forms (Roxithromycin 150 mg tablets (Revised 2018))). (2) As for in vitro, there is a report of negative results in a bacterial reverse mutation test, and a mouse lymphoma test and an unscheduled DNA synthesis test with cultured mammalian cells (Pharmaceutical Interview Forms (Roxithromycin 150 mg tablets (Revised 2018))).
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) and (2), it was classified in Category 2. In addition, based on (3), "additional category for effects on or via lactation" was added to the classification. [Evidence Data] (1) Based on a report of increased frequencies of fetal external and skeletal abnormalities in rats at doses about 80 times higher than the clinical doses, it is described that "pregnant women or women who may be pregnant should be administered this drug only if the expected therapeutic benefits outweigh the possible risks associated with treatment" (Ethical Pharmaceuticals 2017 (2016)). (2) An increase in the number of fetal deaths, growth retardation, and external and skeletal abnormalities were observed at doses where toxicities such as general condition worsening were manifested in maternal animals in a test with rats dosed orally during organogenesis (Pharmaceutical Interview Forms (Roxithromycin 150 mg tablets (Revised 2018))). (3) There is a description that "Administration to lactating women should be avoided, and breast-feeding should be discontinued when administration to a breast-feeding woman is inevitable" based on a report that transfer of this substance in milk was observed in rats (Ethical Pharmaceuticals 2017 (2016)).
8	Specific target organ toxicity - Single exposure	Category 1 (blood system, gastrointestinal tract, liver)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	[Rationale for the Classification] This substance is a macrolide antibiotic and is a drug used in the treatment of various bacterial infections by oral administration. In a single dose clinical test in (1), symptoms of the gastrointestinal tract and blood system were observed, and in (2), although the number of doses is unknown, symptoms of the gastrointestinal tract and liver were observed as side effects, therefore, it was classified in Category 1 (blood system, gastrointestinal tract, liver). As for eosinophilia in (2), it was not adopted as evidence because there is a possibility of changes due to hypersensitivity, etc. [Evidence Data] (1) In a clinical pharmacology/tolerability test, when healthy adult men (total of 24 subjects) were given a single oral dose at 300 mg (potency), diarrhea (1 subject), loose stool (2 subjects) and increased reticulocytes (3 subjects) were observed (Pharmaceutical Interview Forms (Roxithromycin 150 mg tablets (Revised 2018))). (2) Although the number of doses is unknown, the main side effects observed were hematological (eosinophilia), hepatic (increased AST, ALT, ALP, etc.) and gastrointestinal (stomach discomfort, abdominal pain, diarrhea, vomiting, etc.) symptoms at a frequency of 0.1 to < 5% (Ethical Pharmaceuticals 2017 (2016)). [Reference Data, etc.] (3) As for serious side effects (incidences were unknown in every case), QT prolongation, ventricular tachycardia (including Torsades de pointes) or ventricular fibrillation, fulminant hepatitis, hepatic dysfunction, jaundice or hepatic failure, thrombocytopenia, pancytopenia, hemolytic anemia, leukopenia or agranulocytosis, PIE syndrome/interstitial pneumonia, pseudomembranous colitis or hemorrhagic colitis, rhabdomyolysis, convulsion, and acute nephropathy or tubulointerstitial nephritis, etc. were reported (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), major side effects were observed in the gastrointestinal tract and liver. Therefore, it was classified in Category 1 (gastrointestinal tract, liver). [Evidence Data] (1) In humans, side effects (including abnormal laboratory values) were observed in 202 cases (2.27%) out of 8,903 of total cases. The major side effects were increased ALT in 42 cases (0.47%), increased AST in 32 cases (0.36%), eosinophilia in 24 cases (0.27%), diarrhea in 14 cases (0.16%) and stomach discomfort in 13 cases (0.15%) (Ethical Pharmaceuticals 2017 (2016)). Eosinophilia was not adopted as evidence because of the possibility of changes due to hypersensitivity, etc. [Reference Data, etc.] (2) It is reported that as for serious side effects in humans (incidences were unknown in every case), shock or anaphylaxis, pseudomembranous colitis or hemorrhagic colitis, interstitial pneumonia, thrombocytopenia, hepatic dysfunction or jaundice, oculomucocutaneous syndrome (Stevens-Johnson syndrome), and QT prolongation or ventricular tachycardia (including Torsades de pointes) may appear (Ethical Pharmaceuticals 2017 (2016)). (3) In a 6-month repeated dose toxicity test with dogs by the oral route, decreases in body weight and food consumption, increases in ALT (GPT) and ALP, fibrosis of the liver and bile duct tissues, bile duct hyperplasia, and atrophy of the testes and prostate were observed at 100 mg/kg/day (within the range of Category 2) (Pharmaceutical Interview Forms (Roxithromycin 150 mg tablets (Revised 2018))).
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 = 0.047 mg/L for algae (Pseudokirchneriella subcapitata) (Environmental Risk Assessment for Chemical Substances Vol. 17 (Ministry of the Environment, 2019)).
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 = 0.01 mg/L for algae (Pseudokirchneriella subcapitata) (Environmental Risk Assessment for Chemical Substances Vol. 17 (Ministry of the Environment, 2019)). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained, then it is classified in Category 3 due to being not rapidly degradable (BIOWIN), and 48-hour EC50 = 74.3 mg/L for crustacea (Daphnia magna) (Environmental Risk Assessment for Chemical Substances Vol. 17 (Ministry of the Environment, 2019)). 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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