GHS Classification Results by the Japanese Government

日本語で表示



GENERAL INFORMATION
Item Information
CAS RN 57-92-1
Chemical Name 1,-((1R,2R,3S,4R,5R,6S)-4-((2R,3R,4R,5S)-3-((2S,3S,4S,5R,6S)-4,5-dihydroxy-6-(hydroxymethyl)-3-(methylamino)tetrahydro-2H-pyran-2-yloxy)-4-formyl-4-hydroxy-5-methyltetrahydrofuran-2-yloxy)-2,5,6-trihydroxycyclohexane-1,3-diyl)diguanidine; Streptomycin
Substance ID R02-A-075-METI
Classification year (FY) FY2020
Ministry who conducted the classification Ministry of Economy, Trade and Industry (METI)
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 (FY2019 revised edition (Ver. 2.0))
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 Not classified (Not applicable)
-
-
- - There are no chemical groups associated with explosive properties present in the molecule.
2 Flammable gases Not classified (Not applicable)
-
-
- - Solid (GHS definition)
3 Aerosols Not classified (Not applicable)
-
-
- - Not aerosol products.
4 Oxidizing gases Not classified (Not applicable)
-
-
- - Solid (GHS definition)
5 Gases under pressure Not classified (Not applicable)
-
-
- - Solid (GHS definition)
6 Flammable liquids Not classified (Not applicable)
-
-
- - Solid (GHS definition)
7 Flammable solids Classification not possible
-
-
- - No data available.
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.
9 Pyrophoric liquids Not classified (Not applicable)
-
-
- - Solid (GHS definition)
10 Pyrophoric solids Classification not possible
-
-
- - No data available.
11 Self-heating substances and mixtures Classification not possible
-
-
- - No data available.
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).
13 Oxidizing liquids Not classified (Not applicable)
-
-
- - Solid (GHS definition)
14 Oxidizing solids Not classified (Not applicable)
-
-
- - The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is chemically bonded only to carbon or hydrogen.
15 Organic peroxides Not classified (Not applicable)
-
-
- - Organic compounds containing no bivalent -O-O- structure in the molecule.
16 Corrosive to metals Classification not possible
-
-
- - Test methods applicable to solid substances are not available.
17 Desensitized explosives Not classified (Not applicable)
-
-
- - There are no chemical groups associated with explosive properties present in the molecule.

HEALTH HAZARDS
Hazard class Classification Pictogram
Signal word
Hazard statement
(code)
Precautionary statement
(code)
Rationale for the classification
1 Acute toxicity (Oral) Not classified
-
-
- - [Rationale for the Classification]
It was classified as "Not classified" from (1).

[Evidence Data]
(1) LD50 for rats: 9,000 mg/kg (EPA Pesticides RED (1992))
1 Acute toxicity (Dermal) Classification not possible
-
-
- - [Rationale for the Classification]
Classification not possible due to lack of data.
1 Acute toxicity (Inhalation: Gases) Not classified
-
-
- - [Rationale for the Classification]
Solid (GHS definition). It was classified as "Not classified."
1 Acute toxicity (Inhalation: Vapours) Classification not possible
-
-
- - [Rationale for the Classification]
Classification not possible due to lack of data.
1 Acute toxicity (Inhalation: Dusts and mists) Classification not possible
-
-
- - [Rationale for the Classification]
Classification not possible due to lack of data.
2 Skin corrosion/irritation Classification not possible
-
-
- - [Rationale for the Classification]
Classification not possible due to lack of data.
3 Serious eye damage/eye irritation Classification not possible
-
-
- - [Rationale for the Classification]
Classification not possible due to lack of data.
4 Respiratory sensitization Classification not possible
-
-
- - [Rationale for the Classification]
Classification not possible due to lack of data.
4 Skin sensitization Category 1


Warning
H317 P302+P352
P333+P313
P362+P364
P261
P272
P280
P321
P501
[Rationale for the Classification]
It was classified in Category 1 from (1), (2).

[Evidence Data]
(1) Cutaneous and general hypersensitivity reactions were common with this substance and can be severe. The most common features are rash and fever (WHO FAS (1995)).
(2) Hypersensitivity reactions may occur in response to the treatment with this substance, and skin reactions are reported to occur in 5% of patients. Severe exfoliative dermatitis and anaphylaxis have occurred. Sensitization is common among those handling this substance occupationally (WHO FAS (1995)).
5 Germ cell mutagenicity Classification not possible
-
-
- - [Rationale for the Classification]
Classification was not possible due to lack of data.

[Reference Data, etc.]
(1) In a chromosomal aberration test using the human lymphocytes, negative results or equivocal results were reported (WHO FAS 34 (1995)).
(2) In an in vitro mammalian cell chromosome aberration test, positive results were reported (WHO FAS 34 (1995)).
(3) It was negative in two reports on chromosomal aberration tests with the lymphocytes obtained from tuberculosis patients after the treatment by the combined use of this substance and other substances (WHO FAS 34 (1995)).
6 Carcinogenicity Classification not possible
-
-
- - [Rationale for the Classification]
Classification was not possible due to lack of data.

[Reference Data, etc.]
(1) In a 2-year chronic toxicity study with rats dosed by feeding with dihydrostreptomycin (CAS RN 128-46-1), which was a derivative of this substance, as a test substance, a reduction in body weight gain was observed in males at the highest dose of 10 mg/kg/day. No carcinogenicity was observed (EPA Pesticides RED (1992)).
7 Reproductive toxicity Category 1A


Danger
H360 P308+P313
P201
P202
P280
P405
P501
[Rationale for the Classification]
Based on (1) to (3), it was classified in Category 1A. It was reported that children may be born with hearing loss or inner ear problems from the treatment of the mother with this substance during pregnancy.

[Evidence Data]
(1) This substance was also used to treat pregnant women for the first 30 years after marketing. It was known that children may be born with hearing loss or inner ear problems from the treatment of the mother with this substance during pregnancy, and it was possible that the developing fetus was more sensitive than the mother to inner ear toxicity of this substance. Some children of the mothers treated during pregnancy with this substance were born with hearing deficits, but it was presumed that there was no evidence of hearing loss in the mothers during the treatment. These effects occurred after the treatment at pharmacological doses of approximately 15 mg/kg/day by the intramuscular injectable route of exposure, and this corresponded to approximately 1,500 mg/kg/day by the oral route, with 1% oral absorption (EPA Pesticides TRED (2006)).
(2) The microbiological evaluation after intramuscular injection of this substance to female mice (gestation period, 250 mg/kg/time, 2 times/day) suggested the placental transfer to the tissue fluids of embryos (WHO FAS 34 (1995)).
(3) In the tests for examining auditory effects in F1 offspring which were born after intramuscular injection of this substance to female mice (days 12-16 of gestation, 250 mg/kg/day), a reduction in vestibular function was observed in narrow path and rotor rod tests. Morphological abnormalities (degeneration and polyp-like cytoplasmic extrusions of the hair cells) were observed by scanning electron microscopy of the inner ear (WHO FAS 34 (1995)).

[Reference Data, etc.]
(4) With respect to the incidence of congenital malformations in newborns, a group of 1,619 mothers who had received treatment for tuberculosis with this substance, hydrazide, and p-amino salicylic acid were compared to a control group (2,711 healthy pregnant women). The incidence of congenital malformations was 2.34% in tuberculosis infected subjects and 2.56% in the control group, and no difference was observed in the pattern of malformations in the 2 groups. The details of malformations, and the period and time of treatment were not described (WHO FAS 34 (1995)).
8 Specific target organ toxicity - Single exposure Classification not possible
-
-
- - [Rationale for the Classification]
Classification was not possible due to lack of data.
9 Specific target organ toxicity - Repeated exposure Category 1 (auditory organ, nervous system, blood system, kidney, skin)


Danger
H372 P260
P264
P270
P314
P501
[Rationale for the Classification]
Based on (1) to (5), it was classified in Category 1 (sensory organ (auditory organ), nervous system, blood system, liver, kidney, skin)).

[Evidence Data]
(1) In a retrospective epidemiological study of patients presenting with ototoxic side effects after the treatment with this substance under various clinical conditions, vertigo was reported by the end of the first week of the treatment in 25/26 patients treated with this substance alone at doses between 0.25 and 2 g/person/day (3-36 mg/kg/day) (JACFA (1995)).
(2) Findings of renal tubular dysfunctions, such as urinary casts and a minor degree of albuminuria, were not uncommon in humans treated with this substance. However, severe renal damage (proximal tubular necrosis) was rare. It was reported that renal damage was usually reversible on cessation of therapy, and this substance was the least nephrotoxic of the aminoglycosides (JACFA (1995)).
(3) This substance caused toxic neuritis of the branches of the trigeminal nerve resulting in numbness, tingling or burning sensations in the face or mouth. In addition, exfoliative dermatitis, systemic lupus erythematosus, purpura, and other skin diseases were reported (JACFA (1995)).
(4) It was reported that the treatment with this substance caused blood problems (neutropenia, agranulocytosis, aplastic anemia), and liver dysfunction (transient elevation of hepatic enzymes) in some cases (JACFA (1995)).
(5) As serious side effects of streptomycin sulfate (CAS RN 3810-74-0) as an ethical drug, which was a sulfate of this substance, the followings were cited: [1] 8th cranial nerve disorders (mainly vestibular dysfunctions) such as hearing loss, tinnitus, and vertigo, [2] serious renal damages such as acute renal failure, [3] shock, anaphylaxis-like symptom, [4] toxic epidermal necrolysis, [5] interstitial pneumonitis, [6] hemolytic anemia, thrombocytopenia, and [7] liver dysfunction, jaundice (Ethical Pharmaceuticals (2019)).
10 Aspiration hazard Classification not possible
-
-
- - [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) -
-
-
- - -
11 Hazardous to the aquatic environment Long term (Chronic) -
-
-
- - -
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.

To GHS Information