Latest GHS Classification Results by the Japanese Government (edited by NITE)

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GENERAL INFORMATION
 
Item Information
CAS RN 91-23-6
Chemical Name Benzene, 1-methoxy-2-nitro-
Substance ID m-nite-91-23-6_v2
Download of Excel format Excel file

REFERENCE INFORMATION
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) MHLW Website (in Japanese Only)
Sample SDS by MHLW (External link) MHLW Website (in Japanese Only)
OECD/eChemPortal (External link) To OECD/eChemPortal (External link)

PHYSICAL HAZARDS
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
-
-
- - There is a chemical group associated with explosive properties (N-O) present in the molecule, but because it is classified in Division 6.1, PG III in UNRTDG (UN 2730), it was considered to be not applicable to explosives, hazards of the highest precedence, therefore, it was classified as "Not classified." Besides, the calculated oxygen balance is -152. FY2021 GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
2 Flammable gases Not classified (Not applicable)
-
-
- - Liquid (GHS definition)
FY2021 GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
3 Aerosols Not classified (Not applicable)
-
-
- - Not aerosol products. FY2021 GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
4 Oxidizing gases Not classified (Not applicable)
-
-
- - Liquid (GHS definition) FY2021 GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
5 Gases under pressure Not classified (Not applicable)
-
-
- - Liquid (GHS definition) FY2021 GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
6 Flammable liquids Not classified
-
-
- - A flash point is 142 deg C (Closed cup) (HSDB in PubChem (Accessed Oct 2021)). FY2021 GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
7 Flammable solids Not classified (Not applicable)
-
-
- - Liquid (GHS definition) FY2021 GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
8 Self-reactive substances and mixtures Type G
-
-
- - There is a chemical group associated with explosive properties (N-O) present in the molecule, but because it is classified in Division 6.1, PG III in UNRTDG (UN 2730), it does not correspond to self-reactive substances and mixtures, hazards of the highest precedence, therefore, it was classified in Type G. FY2021 GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
9 Pyrophoric liquids Not classified
-
-
- - It is estimated that it does not ignite at normal temperatures from an autoignition temperature of 464 deg C (ICSC (2004), HSDB in PubChem (Accessed Oct 2021)). FY2021 GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
10 Pyrophoric solids Not classified (Not applicable)
-
-
- - Liquid (GHS definition) FY2021 GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
11 Self-heating substances and mixtures Classification not possible
-
-
- - Test methods applicable to liquid substances are not available. FY2021 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). FY2021 GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
13 Oxidizing liquids Not classified
-
-
- - The substance is an organic compound containing chlorine and oxygen (but not fluorine), and the oxygen is chemically bonded to the element other than carbon or hydrogen (N). But because it is classified in Division 6.1, PG III in UNRTDG (UN 2730), it does not correspond to oxidizing liquids, hazards of the highest precedence, therefore, it was classified as "Not classified." FY2021 GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
14 Oxidizing solids Not classified (Not applicable)
-
-
- - Liquid (GHS definition) FY2021 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.
FY2021 GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
16 Corrosive to metals Classification not possible
-
-
- - No data available.
FY2021 GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
17 Desensitized explosives Not classified
-
-
- - There is a chemical group associated with explosive properties (N-O) present in the molecule, but because it is classified in Division 6.1, PG III in UNRTDG (UN 2730), it was considered to be not applicable to explosives, hazards of the highest precedence, therefore, it was classified as "Not classified." FY2021 GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))

HEALTH HAZARDS
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) Category 4


Warning
H302 P301+P312
P264
P270
P330
P501
[Rationale for the Classification]
Based on (1) to (8), it was classified in Category 4.

[Evidence Data]
(1) LD50 for rats: between 740 to 1,000 mg/kg (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2011))
(2) LD50 for rats: 740 mg/kg (Patty (6th, 2012))
(3) LD50 for rats (males): 760 mg/kg (DFG MAK (1998))
(4) LD50 for rats (females): 740 mg/kg (DFG MAK (1998))
(5) LD50 for rats: 874 mg/kg (DFG MAK (1998))
(6) LD50 for rats (males): 1,000 mg/kg (DFG MAK (1998))
(7) LD50 for rats (females): 890 mg/kg (DFG MAK (1998))
(8) LD50 for rats: 1,980 mg/kg (DFG MAK (1998))
FY2021 GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
1 Acute toxicity (Dermal) Not classified
-
-
- - [Rationale for the Classification]
Based on (1), it was classified as "Not classified."

[Evidence Data]
(1) LD50 for rats: > 2,000 mg/kg (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2011), DFG MAK (1998))
FY2021 GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
1 Acute toxicity (Inhalation: Gases) Not classified (Not applicable)
-
-
- - [Rationale for the Classification]
Liquid (GHS definition). It was classified as "Not classified."
FY2021 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.
FY2021 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.
FY2021 GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
2 Skin corrosion/irritation Not classified
-
-
- - [Rationale for the Classification]
Based on (1), it was classified as "Not classified."

[Evidence Data]
(1) It was reported that, in a skin irritation test (semiocclusive, 4-hour application) with rabbits (n=6), no irritation reactions were observed (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2011), DFG MAK (1998)).
FY2021 GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
3 Serious eye damage/eye irritation Not classified
-
-
- - [Rationale for the Classification]
Based on (1), it was classified as "Not classified."

[Evidence Data]
(1) It was reported that, in an eye irritation test with rabbits (n=6) (observation for 4 days), swelling and diffuse reddening of the conjunctiva and slight lacrimation were observed after one hour but all signs disappeared after 24 hours (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2011), DFG MAK (1998)).
FY2021 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.
FY2021 GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
4 Skin sensitization Classification not possible
-
-
- - [Rationale for the Classification]
Classification not possible due to lack of data.
FY2021 GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
5 Germ cell mutagenicity Category 2


Warning
H341 P308+P313
P201
P202
P280
P405
P501
[Rationale for the Classification]
Based on (1) and (2), it was classified in Category 2. It was classified based on the new information source.

[Evidence Data]
(1) As for in vivo, negative results were obtained in a micronucleus test using the bone marrow cells of rats, but in an adduct formation test for multiple target organs of rats (intraperitoneal injection, for 5 days, 0.15 mg/kg/day), positive results were observed for the liver, kidney, spleen, and urinary bladder, and negative results were obtained for the lung, heart, and brain. In a comet assay for the kidney, urinary bladder, and liver cells of rats (DNA strand breaks: gavage administration, for 2 days (2 times), up to 750 mg/kg/day), positive results were observed for the kidney (at or above 250 mg/kg/day) and negative results were observed for the others, and in another comet assay (and a modified comet assay with hOGG1) for urinary bladder cells (gavage administration, for 3 days (3 times)), negative or positive results were obtained (IARC 127 (2021)).
(2) As for in vitro, positive results were obtained in multiple bacterial reverse mutation tests, positive results were observed in a mouse lymphoma test, negative results were obtained in a gene mutation test using the Chinese hamster lung (V79) cells, and positive results (mainly, +S9) were obtained in a chromosomal aberration test using the Chinese hamster ovary (CHO) cells, Chinese hamster lung (CHL) cells, and V79 cells (IARC 127 (2021), DFG MAK (1998), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2011), Mutagenicity Test Data of Existing Chemical Substances based on the toxicity investigation system of the Industrial Safety and Health Law (Accessed Nov. 2021)).
FY2021 GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
6 Carcinogenicity Category 1B


Danger
H350 P308+P313
P201
P202
P280
P405
P501
[Rationale for the Classification]
Based on (1) and (2), it was classified in Category 1B, since an increased incidence of malignant tumors was observed in two species of animals and there was sufficient evidence for carcinogenicity in the animal tests. Based on the new information source, the classification result was changed.

[Evidence Data]
(1) In a 2-year (103-week) carcinogenicity study with rats and mice dosed by feeding (GLP, rats: 222 to 2,000 ppm, mice: 666 to 6,000 ppm), an increasing trend in the incidence of mononuclear cell leukemia and a significant increase compared to the control group were observed in both male and female rats; and increased incidences of hepatocellular adenoma, hepatocellular carcinoma, and hepatoblastoma in male mice, and hepatocellular adenoma in female mice were observed (IARC 127 (2021), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2011), DFG MAK (1998), NTP TR416 (1993)).
(2) In a carcinogenicity study (stop-exposure study) in which rats were dosed by feeding for 27 weeks (6,000, 18,000 ppm), then given basal diet, and sacrificed for necropsy at experimental weeks 28, 40, 65, and 103, increases in benign and malignant neoplasms of the urinary bladder, transitional cell neoplasms of the kidney, and benign and malignant neoplasms of the large intestine were observed in males and females (IARC 127 (2021), NTP TR416 (1993)).
(3) As for the classification results by domestic and international organizations, the IARC classified this substance in Group 2A (IARC 127 (2021)), the NTP classified it in R (NTP RoC 14th. (2016)), the Japan Society For Occupational Health (JSOH) classified it in Group 2B (Recommendation of Occupational Exposure Limits (Japan Society For Occupational Health (JSOH), 2021)), the EU classified it in Carc. 1B (EU CLP Classification Results (Accessed November 2021)), the DFG classified it in Category 2 (List of MAK and BAT values 2020 (Accessed November 2021)).

[Reference Data, etc.]
(4) There is strong mechanistic evidence that, in view of the metabolism of this substance to the aromatic amine ortho-anisidine (CAS RN 90-04-0), this substance belongs within a mechanistic class of aromatic amines, several member compounds of which have been classified as carcinogenic to humans. This substance exhibits concordance with aromatic amines with respect to the formation of common DNA-reactive moieties, genotoxicity and target organs of carcinogenicity in chronic animal bioassays (IARC 127 (2021)).
FY2021 GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
7 Reproductive toxicity Category 2


Warning
H361 P308+P313
P201
P202
P280
P405
P501
[Rationale for the Classification]
Based on (1) and (2), since there was a report that suggested developmental effects, it was classified in Category 2.

[Evidence Data]
(1) In a developmental toxicity study with female rats dosed by gavage (20 to 320 mg/kg/day, days 6 to 15 of gestation), at the high dose at which effects on dams (symptoms, decreased food consumption) were observed, a slight increase in resorbed embryos (8.5%, controls: 5.0%) and slight increases in visceral variations and fusions in fetuses were observed (DFG MAK (1989), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2011)).
(2) Based on the effects in (1), the Ministry of Health, Labour and Welfare concluded as "Reproductive and developmental toxicity: Positive" (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2011)).

[Reference Data, etc.]
(3) In a 13-week study with rats dosed by feeding (200 to 18,000 ppm), at the highest dose (18,000 ppm: approx. 900 mg/kg/day), degeneration of the seminiferous tubule epithelium accompanied by loss of spermatogenic cells and decreased numbers of spermatozoa in the testes were observed, while uterine atrophy was observed in female rats (NTP TR416 (1993), DFG MAK (1998), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2011)).
FY2021 GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
8 Specific target organ toxicity - Single exposure Category 2 (systemic)


Warning
H371 P308+P311
P260
P264
P270
P405
P501
[Rationale for the Classification]
Based on (1), since the signs of toxicity in which no target organ could be identified were observed and deaths occurred within the range for Category 2, it was classified in Category 2 (systemic toxicity).

[Evidence Data]
(1) It was reported that, in an acute oral toxicity test with rats, non-specific symptoms of intoxication (such as crouching, prostration, unsteady gait, irregular breathing, ruffled fur, partially closed eye-lids, reduced spontaneous activity, dazed behavior, reduced reflexes and lacrimation) were seen after treatment and the LD50 was 874 mg/kg (within the range for Category 2). In addition, it was reported that necropsy of the animals which died revealed slight reddening of the mucous membranes of the stomach or of the whole gastrointestinal tract, and in some cases, pale kidneys, dark coloration of the adrenal glands, and reddish brown discoloration of the lungs (DFG MAK (1998)).

[Reference Data, etc.]
(2) It was reported that, after an accident involving spillage of 2-nitroanisole at an industrial plant, methemoglobin levels were determined in 50 workers involved in cleaning up the contaminated area and all values were within the normal range (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2011), DFG MAK (1998)).
FY2021 GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
9 Specific target organ toxicity - Repeated exposure Category 2 (kidney)


Warning
H373 P260
P314
P501
[Rationale for the Classification]
Based on (1) and (2), it was classified in Category 2 (kidney). Besides, the blood system effects observed in (3) and (4) were regarded as effects at doses exceeding the range for Category 2 based on the long-term test results and were not adopted for classification.

[Evidence Data]
(1) It was reported that, in a repeated dose 13-week oral toxicity study with rats dosed by feeding, increased absolute liver weight (females), increased absolute kidney weight (males), and kidney effects (multifocal degeneration and necrosis of the renal tubule epithelium with infiltration of mononuclear inflammatory cells (males)) were observed at 200 to 2,000 ppm (10 to 100 mg/kg/day, within the range for Category 2); effects on the urinary bladder (benign/malignant neoplasms, transitional epithelium hyperplasia) were observed at 6,000 ppm (300 mg/kg/day, in the range corresponding to "Not classified"); and effects on the blood (increased methemoglobin), the spleen (congestion, hemosiderin deposits), and the reproductive organs (degeneration of the seminiferous tubule epithelium associated by loss of spermatogenic cells and decreased numbers of spermatozoa in the testes, uterine atrophy) were observed at 18,000 ppm (900 mg/kg/day, in the range corresponding to "Not classified") (DFG MAK (1998), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2011), NTP TR416 (1993)).
(2) It was reported that, in a 2-year combined chronic toxicity/carcinogenicity study with rats dosed by feeding, hyperplasia of the forestomach, hyperplasia of the renal tubule (males), and increased severity of nephropathy (males) were observed at 222 to 2,000 ppm (10 to 80 mg/kg/day (males), 10 to 90 mg/kg/day (females), within the range for Category 2) (NTP TR416 (1993)).

[Reference Data, etc.]
(3) It was reported that, in a repeated dose 28-day oral toxicity study with rats dosed by gavage, hematological changes indicating slight hemolytic anemia and increased spleen weight were observed at 200 mg/kg/day (converted guidance value: 62.2 mg/kg/day, within the range for Category 2) (DFG MAK (1998), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2011)).
(4) It was reported that, in a study in which only one dose (150 mg/kg) was orally administed 30 times to rats (males), slight hemolytic anemia and increased relative liver, kidney, and spleen weight were observed (DFG MAK (1998), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2011)).
(5) It was reported that, in a repeated dose 13-week oral toxicity study with mice dosed by feeding, an increase in the number of animals with hepatocellular hypertrophy (males) and increases in absolute and relative liver weight (females) were observed at 60 to 2,000 ppm (9 to 90 mg/kg/day, within the range for Category 2), and effects on the blood (reduced hemoglobin and hematocrit) were observed at 2,000 and 6,000 ppm (300 and 900 mg/kg/day in the range corresponding to "Not classified") (DFG MAK (1998), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2011)).
(6) It was reported that, in a 2-year combined chronic toxicity/carcinogenicity study with mice dosed by feeding, no nonneoplastic lesions were observed at 6,000 ppm (830 mg/kg/day (males), 1,200 mg/kg/day (females), in the range corresponding to "Not classified") (NTP TR416 (1993)).
FY2021 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.
FY2021 GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))

ENVIRONMENTAL HAZARDS
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 3
-
-
H402 P273
P501
- FY2010 GHS Classification Guidance by the Japanese Government (July, 2010)
11 Hazardous to the aquatic environment Long term (Chronic) Category 3
-
-
H412 P273
P501
- FY2010 GHS Classification Guidance by the Japanese Government (July, 2010)
12 Hazardous to the ozone layer Classification not possible
-
-
- - - FY2010 GHS Classification Guidance by the Japanese Government (July, 2010)


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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