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 | m-nite-57-92-1_v2 |
Download of Excel format | Excel file |
Item | Information |
---|---|
Guidance used for the classification (External link) | To Guidance List |
UN GHS document (External link) | To UN GHS document |
FAQ(GHS classification results by the Japanese Government) | To FAQ |
List of Information Sources (Excel file) | List of Information Sources |
List of Definitions/Abbreviations | Definitions/Abbreviations |
Sample Label by MHLW (External link) | |
Sample SDS by MHLW (External link) | |
OECD/eChemPortal (External link) | To OECD/eChemPortal (External link) |
Hazard class | Classification | Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | Classification year (FY) | GHS Classification Guidance for the Japanese Government | |
---|---|---|---|---|---|---|---|---|
1 | Explosives | Not classified (Not applicable) |
- |
- | - | There are no chemical groups associated with explosive properties present in the molecule. | FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
2 | Flammable gases | Not classified (Not applicable) |
- |
- | - | Solid (GHS definition) | FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
3 | Aerosols | Not classified (Not applicable) |
- |
- | - | Not aerosol products. | FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
4 | Oxidizing gases | Not classified (Not applicable) |
- |
- | - | Solid (GHS definition) | FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
5 | Gases under pressure | Not classified (Not applicable) |
- |
- | - | Solid (GHS definition) | FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
6 | Flammable liquids | Not classified (Not applicable) |
- |
- | - | Solid (GHS definition) | FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
7 | Flammable solids | Classification not possible |
- |
- | - | No data available. | FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
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. | FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
9 | Pyrophoric liquids | Not classified (Not applicable) |
- |
- | - | Solid (GHS definition) | FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
10 | Pyrophoric solids | Classification not possible |
- |
- | - | No data available. | FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
11 | Self-heating substances and mixtures | Classification not possible |
- |
- | - | No data available. | FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
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). | FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
13 | Oxidizing liquids | Not classified (Not applicable) |
- |
- | - | Solid (GHS definition) | FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
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. | FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
15 | Organic peroxides | Not classified (Not applicable) |
- |
- | - | Organic compounds containing no bivalent -O-O- structure in the molecule. | FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
16 | Corrosive to metals | Classification not possible |
- |
- | - | Test methods applicable to solid substances are not available. | FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
17 | Desensitized explosives | Not classified (Not applicable) |
- |
- | - | There are no chemical groups associated with explosive properties present in the molecule. | FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
Hazard class | Classification | Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | Classification year (FY) | GHS Classification Guidance for the Japanese Government | |
---|---|---|---|---|---|---|---|---|
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)) |
FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
1 | Acute toxicity (Dermal) | Classification not possible |
- |
- | - | [Rationale for the Classification] Classification not possible due to lack of data. |
FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
1 | Acute toxicity (Inhalation: Gases) | Not classified |
- |
- | - | [Rationale for the Classification] Solid (GHS definition). It was classified as "Not classified." |
FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
1 | Acute toxicity (Inhalation: Vapours) | Classification not possible |
- |
- | - | [Rationale for the Classification] Classification not possible due to lack of data. |
FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
1 | Acute toxicity (Inhalation: Dusts and mists) | Classification not possible |
- |
- | - | [Rationale for the Classification] Classification not possible due to lack of data. |
FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
2 | Skin corrosion/irritation | Classification not possible |
- |
- | - | [Rationale for the Classification] Classification not possible due to lack of data. |
FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
3 | Serious eye damage/eye irritation | Classification not possible |
- |
- | - | [Rationale for the Classification] Classification not possible due to lack of data. |
FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
4 | Respiratory sensitization | Classification not possible |
- |
- | - | [Rationale for the Classification] Classification not possible due to lack of data. |
FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
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)). |
FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
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)). |
FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
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)). |
FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
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)). |
FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
8 | Specific target organ toxicity - Single exposure | Classification not possible |
- |
- | - | [Rationale for the Classification] Classification was not possible due to lack of data. |
FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
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)). |
FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
10 | Aspiration hazard | Classification not possible |
- |
- | - | [Rationale for the Classification] Classification not possible due to lack of data. |
FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
Hazard class | Classification | Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | Classification year (FY) | GHS Classification Guidance for the Japanese Government | |
---|---|---|---|---|---|---|---|---|
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 = 0.419 mg/L for algae (Raphidocelis subcapitata) (test substance: Streptomycin sulphate, Document for registration standards for agricultural chemicals set by the Minister of Environment to prevent harm to animals and plants in areas of public waters, 2015). | FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
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 NOErC = 0.019 mg/L for algae (Raphidocelis subcapitata) (test substance: Streptomycin sulphate, Document for registration standards for agricultural chemicals set by the Minister of Environment to prevent harm to animals and plants in areas of public waters, 2015). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained (crustacea, fish), then it is classified in Category 3 due to being not rapidly degradable, and 48-hour EC50 = 42 mg/L for crustacea (Daphnia magna) (test substance: Streptomycin sulphate, Document for registration standards for agricultural chemicals set by the Minister of Environment to prevent harm to animals and plants in areas of public waters, 2015). By drawing a comparison between the above results, it was classified in Category 1. |
FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
12 | Hazardous to the ozone layer | Classification not possible |
- |
- | - | This substance is not listed in the Annexes to the Montreal Protocol. | FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
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