NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	113378-31-7
Chemical Name	Semduramicin
Substance ID	R01-B-121
Classification year (FY)	FY2019
Ministry who conducted the classification	Ministry of Health, Labour and Welfare (MHLW)/Ministry of the Environment (MOE)
New/Revised	Revised
Classification result in other fiscal year	FY2006
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)	MHLW Website (in Japanese Only)
Model SDS by MHLW (External link)	MHLW Website (in Japanese Only)
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 present in the molecule associated with explosive or self-reactive properties. 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 2	Danger	H300	P301+P310 P264 P270 P321 P330 P405 P501	[Rationale for the Classification] Based on (1), it was classified in Category 2. Besides, the category was changed from the previous classification by using the new information source. [Evidence Data] (1) LD50 (semduramicin sodium, CAS RN 119068-77-8) for rats: male: 66 mg/kg (a converted value equivalent to this substance: 64 mg/kg), 50-100 mg/kg (a converted value equivalent to this substance: 49-98 mg/kg), female: 46 mg/kg (a converted value equivalent to this substance: 45 mg/kg), 5-20 mg/kg (a converted value equivalent to this substance: 5-20 mg/kg) (Risk Assessment Report (Veterinary Medicinal Products and Feed Additives) (Food Safety Commission of Japan, 2017))
1	Acute toxicity (Dermal)	*	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." [Evidence Data] (1) LD50 (semduramicin sodium, CAS RN 119068-77-8) for rats: >5,000 mg/kg (a converted value equivalent to this substance: 4,877 mg/kg) (Risk Assessment Report (Veterinary Medicinal Products and Feed Additives) (Food Safety Commission of Japan, 2017)).
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)	Category 2	Danger	H330	P304+P340 P403+P233 P260 P271 P284 P310 P320 P405 P501	[Rationale for the Classification] Based on (1), it was classified in Category 2. Besides, exposure concentrations were higher than the saturated vapor concentration (0.00000047 mg/L), therefore, the reference value in units of mg/L was applied as a dust. The category was changed from the previous classification by using the new information source. [Evidence Data] (1) LC50 (semduramicin sodium, CAS RN 119068-77-8) for rats: male: 82 mg/m3 (a converted value equivalent to this substance: 80 mg/m3 (0.08 mg/L)), female: 53 mg/m3 (a converted value equivalent to this substance: 52 mg/m3 (0.052 mg/L)) (Risk Assessment Report (Veterinary Medicinal Products and Feed Additives) (Food Safety Commission of Japan, 2017))
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] There are no in vivo data for this substance, however, based on in vitro data in (1), and data in (2) and (3) of semduramicin sodium (CAS RN 119068-77-8) which is a sodium salt of this substance, it was classified as "Not classified." The classification result was changed from the previous classification by using the new information source. [Evidence Data] (1) As in vitro data for this substance, there is a negative report in a bacterial reverse mutation test (Risk Assessment Report (Veterinary Medicinal Products and Feed Additives) (Food Safety Commission of Japan, 2017)). (2) There is a negative report in an in vivo chromosomal aberration test of semduramicin sodium in mouse bone marrow cells (Risk Assessment Report (Veterinary Medicinal Products and Feed Additives) (Food Safety Commission of Japan, 2017)). (3) As for in vitro tests on semduramicin sodium, there are negative reports in a bacterial reverse mutation test, and a gene mutation test and unscheduled DNA synthesis test with cultured mammalian cells, and a chromosomal aberration test using human lymphocyte (Risk Assessment Report (Veterinary Medicinal Products and Feed Additives) (Food Safety Commission of Japan, 2017)).
6	Carcinogenicity	*	- -	-	-	[Rationale for the Classification] There are no classification results by domestic and international organizations. There is no report available on humans. Based on (1) and (2), it was classified as "Classification not possible." [Evidence Data] (1) In a 2-year study with rats fed with the sodium salt of this substance (CAS RN 119068-77-8), although tumors were observed in the treated groups and the control group, no dose-dependency was observed, and it was not thought to be an effect of the administration (Risk Assessment Report (Veterinary Medicinal Products and Feed Additives) (Food Safety Commission of Japan, 2017)). (2) In a chronic toxicity/carcinogenicity test with rats orally administered this substance for 2 years, no carcinogenicity was observed (Risk Assessment Report (Veterinary Medicinal Products and Feed Additives) (Food Safety Commission of Japan, 2017)).
7	Reproductive toxicity	*	- -	-	-	-
8	Specific target organ toxicity - Single exposure	Category 1 (nervous system)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	[Rationale for the Classification] There are no data on this substance itself, however, based on data in (1) of semduramicin sodium (CAS RN 119068-77-8) which is the sodium salt of this substance, it was classified in Category 1 (nervous system). The classification result was changed from the previous classification by using the new information source. [Evidence Data] (1) In a test in which mice were given a single oral administration of semduramicin sodium, decreased locomotor activity, dyspnea, ptosis, prone position, clonic convulsion and hindlimb paralysis were observed, but these symptoms disappeared 3-4 days after the administration in the survived animals. There is no description of the lowest dose at which effects were observed, however, it was considered to be around LD50 values (122 mg/kg (male) and 140 mg/kg (female), a converted value equivalent to this substance: 119 mg/kg (male) and 136 mg/kg (female)), which correspond to the range of Category 1 (Risk Assessment Report (Veterinary Medicinal Products and Feed Additives) (Food Safety Commission of Japan, 2017)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (nervous system, eye, muscle)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] There are no data on this substance, however, based on data in (1)-(4) on semduramicin sodium (CAS RN 119068-77-8), it was classified in Category 1 (nervous system, eye, muscle). Besides, with regard to the effects on the eyes, since lesions were also observed in the non-tapetum region, it was judged that the eyes could be a target organ in humans who do not have tapetum. After the review using the new information source, the classification result was changed from the previous classification. [Evidence Data] (1) In a 91-day repeated oral dose toxicity test with rats dosed by feeding, reduced body weight gain, decreased food consumption, rough fur coat, emaciation, decreased intraperitoneal fat, increased total serum cholesterol, decreased blood glucose, etc. were observed at 2.25 mg/kg/day (within the range of Category 1) (Risk Assessment Report (Veterinary Medicinal Products and Feed Additives) (Food Safety Commission of Japan, 2017)). (2) In a 1-month feeding study with dogs dosed by feeding, muscle degeneration and necrosis, increases in AST and ALT in 1 out of 4 animals and an increase in CPK in all (4 animals) were found at 2 mg/kg/day (converted guidance value: 0.67 mg/kg/day, within the range of Category 1), and at 4 mg/kg/day (converted guidance value: 1.33 mg/kg/day, within the range of Category 1), progressive ataxia (temporary dysstasia and difficulty in walking in 2 animals, irreversible dysstasia in other 2 animals) and muscle degeneration/necrosis and nerve damage (all animals), and increases in CPK, AST, ALP (all animals) were observed (Risk Assessment Report (Veterinary Medicinal Products and Feed Additives) (Food Safety Commission of Japan, 2017)). (3) In a 182-day repeated dose toxicity test with dogs dosed by feeding, small circular spots were observed in the retinal tapetum at 1.0 mg/kg/day (within the range of Category 1) (Risk Assessment Report (Veterinary Medicinal Products and Feed Additives) (Food Safety Commission of Japan, 2017)). (4) In a 1-year repeated dose toxicity test with dogs dosed by feeding, circular spots in the retinal tapetum, hyaline degeneration and separation of the retinal rod cells and cone cells in the retinal tapetum and non-tapetum regions, retinal detachment, swelling or degeneration of mitochondria in the rod-shaped cells and cone-shaped cells, and decay of the outer segment disk, etc. were observed at 1.0 mg/kg/day (within the range of Category 1) (Risk Assessment Report (Veterinary Medicinal Products and Feed Additives) (Food Safety Commission of Japan, 2017)).
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)	Classification not possible	- -	-	-	Classification not possible due to lack of data.
11	Hazardous to the aquatic environment Long term (Chronic)	Classification not possible	- -	-	-	Classification not possible due to lack of data.
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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