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GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	1937-37-7
Chemical Name	Disodium 4-amino-3-[4'-(2,4-diaminophenylazo)-1,1'-biphenyl-4-ylazo]-5-hydroxy-6-phenylazo-2,7-naphthalenedisulfonate (C.I. Direct Black 38)
Substance ID	H30-B-009-METI, MOE
Classification year (FY)	FY2018
Ministry who conducted the classification	Ministry of Economy, Trade and Industry (METI)/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	Not applicable	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule.
2	Flammable gases (including chemically unstable gases)	Not applicable	- -	-	-	Solid (GHS definition)
3	Aerosols	Not applicable	- -	-	-	Not aerosol products.
4	Oxidizing gases	Not applicable	- -	-	-	Solid (GHS definition)
5	Gases under pressure	Not applicable	- -	-	-	Solid (GHS definition)
6	Flammable liquids	Not applicable	- -	-	-	Solid (GHS definition)
7	Flammable solids	Classification not possible	- -	-	-	No data available.
8	Self-reactive substances and mixtures	Not applicable	- -	-	-	There are no chemical groups present in the molecule associated with explosive or self-reactive properties.
9	Pyrophoric liquids	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	- -	-	-	There is a metal (Na) present in the molecule. However, because there is an observation result that it is soluble in water (HSDB (2018)), it is estimated that it does not react vigorously with water.
13	Oxidizing liquids	Not applicable	- -	-	-	Solid (GHS definition)
14	Oxidizing solids	Classification not possible	- -	-	-	It is an organic compound which does not contain fluorine or chlorine but contains oxygen, and the oxygen is chemically bonded to the element other than carbon or hydrogen (S). However, the classification is not possible due to no data.
15	Organic peroxides	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.

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] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) LD50 for rats: > 2,000 mg/kg (NICNAS IMAP (Accessed Dec. 2018)) (2) LD50 for rats: 7,600 mg/kg (HSDB (2003))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) LD50 for rats: > 2,000 mg/kg (NICNAS IMAP (Accessed Dec. 2018)) (2) LD50 for rabbits: > 8,000 mg/kg (HSDB (2003))
1	Acute toxicity (Inhalation: Gases)	Not applicable	- -	-	-	[Rationale for the Classification] Solid (GHS definition)
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)	Not classified	- -	-	-	[Rationale for the Classification] Based on (1), since LC50 was considered to be greater than approx. 45 mg/L (converted 4-hour equivalent value), it was classified as "Not classified." [Evidence Data] (1) There is a report that as a result of one-hour inhalation exposure of rats to about 180 mg/L, 1/10 died (HSDB (2003)).
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. Besides, the evidence in the previous classification was not used for classification because the details of the data were unknown.
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
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 according to the GHS Classification Guidance for the Japanese Government. Besides, the category was changed from the previous category due to the revision of information sources. [Evidence Data] (1) As for in vivo, positive results were obtained in an unscheduled DNA synthesis test with rat hepatocytes and a micronucleus test with rat bone marrow cells (HSDB (2003)). (2) As for in vitro, in a bacterial reverse mutation test, a positive result was obtained under a metabolic activation system (IARC 99 (2010)). [Reference Data, etc.] (3) In workers exposed to benzidine or benzidine-based azo dyes containing this substance, a dose-dependent increase in the count of peripheral lymphocytes suggesting chromosomal aberrations was observed (NICNAS IMAP (Accessed Dec. 2018)).
6	Carcinogenicity	Category 1A	Danger	H350	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] This substance (Direct Black 38) is a benzidine-based azo dye in terms of chemical structure and is metabolized to form benzidine. Based on (1), dyes metabolized to benzidine including this substance were classified in Group 1 by IARC, and as K by NTP. There is insufficient evidence for carcinogenicity in humans from (4), but in experimental animals, according to (2) and (3), there is evidence that this substance is carcinogenic through the oral route. From the above, it was classified in Category 1A based on the classification results of benzidine-based dyes by IARC and NTP. [Evidence Data] (1) Since benzidine was classified in Group 1, and benzidine-based dyes are metabolized to produce benzidine in both humans and experimental animals, this means that exposure to these dyes has effects similar to those of benzidine, dyes that are metabolized to form benzidine, including this substance were classified in Group 1 by IARC (IARC 99 (2010), IARC 100F (2012)). In addition, it was classified as K (Known to be human carcinogen) by NTP (NTP Roc Background Document (1999), NTP RoC (14th, 2014)). (2) As a result of administering this substance by feeding to rats for 13 weeks, in males, increases in the incidence of hepatocellular carcinoma and neoplastic nodules of the liver, and also in females, increases in the incidence of neoplastic nodules of the liver were observed (NTP TR 108 (1979), IARC 100F (2012)). (3) As a result of administering this substance by drinking water to mice for 60 weeks, significant increases in the incidence of hepatocellular carcinoma and mammary gland carcinoma were observed (IARC 100F (2012)). [Reference Data, etc.] (4) Although IARC investigated six epidemiological study reports on an increased risk of urinary bladder cancer in occupational exposure to dyes metabolized to benzidine, including this substance, consistent results were not obtained, and quantitative data were also not provided. Therefore. IARC concluded that the evidence in humans was inadequate (IARC 99 (2010), IARC 100F (2012)). (5) In the EU CLP, this substance is grouped into benzidine-based dyes, but it was classified in Carc. 1B for carcinogenicity classification (Proposal for identification of SVHC (2013)). It was classified in Group 2A by the Japan Society For Occupational Health (OEL Documentations (Carcinogenicity classification) (Japan Society For Occupational Health (JSOH, 2001))). (6) The Ministry of Health, Labour and Welfare designated azo dyes that may be metabolized to produce 24 aromatic amines including benzidine as objects of the regulation under the revised Act on the Control of Household Products Containing Harmful Substances, and it has been in force since April 2016 (website of the Ministry of Health, Labour and Welfare (Accessed Dec. 2018)).
7	Reproductive toxicity	Category 2	Warning	H361	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1), as the postnatal developmental effects in a test with pregnant mice, adverse effects on genetic organs and spermatogenesis in male pups are reported. However, there is no description of the general toxic effects on parental animals, and it cannot be determined whether they are secondary effects of toxic effects on parental animals. In (2), which is the United States TSCA application data, although the species and route of administration are unknown, there is a report that an increase in the incidence of malformations at the general toxic dose of maternal animals was observed in the teratogenicity test with pregnant animals. Therefore, it was classified in Category 2 for this hazard class. [Evidence Data] (1) As a result of oral administration of 500 or 1,000 mg/kg/day to mice of gestational Day 8-12, decreased testicular weight, seminiferous tubule atrophy, and germ cell defects in the seminiferous tubules were observed (NICNAS IMAP (Accessed Dec. 2018)). (2) As TSCA application data, as a result of administration (route unknown) to maternal animals (animal species unknown) of gestational Day 6-15, increases in the embryo/fetus resorptions, in incidences of fetal malformations, and in skeletal malformations were observed at a dose (100 mg/kg/day) where increased liver weight was observed in maternal animals (HSDB (2003)). [Reference Data, etc.] (3) As a result of subcutaneous administration of about 40 mg/kg/day to rats of gestational Day 7-9, although 3 out of maternal animals (16 animals) died, and complete embryo absorptions were observed in 4 animals, no malformations were observed in surviving fetuses (IARC 29 (1982)). (4) It was classified in Repr. 2 by EU CLP.
8	Specific target organ toxicity - Single exposure	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. Besides, the target organ cannot be identified from (1) where the limit dose beyond the range of Category 2 was administered. [Reference Data, etc.] (1) There is a report that in a single oral dose test in which more than 2,000 mg/kg was administered to rats, decreased motor activity, prostration, and convulsions were observed, and at autopsy, congestion of the liver and adrenal glands was observed (NCNAS IMAP (Accessed Dec. 2018)).
9	Specific target organ toxicity - Repeated exposure	Category 2 (liver, kidney, urinary bladder)	Warning	H373	P260 P314 P501	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 2 (liver, kidney, urinary bladder). The target organ was added from the previous classification by using new information sources. [Evidence Data] (1) There is a report that in a 13-week study with rats dosed by feeding (dose: 190 ppm-3,000 ppm, 6 males died at 1,500 ppm and all males and females died at 3,000 ppm), effects on the liver (altered hepatocellular foci, basophilic altered hepatocellular foci, hyperplasia of the bile duct, portal fibrosis) were found at 375 ppm-1,500 ppm (converted value: 18.8-75 mg/kg/day, within the range of Category 2), and glomerulonephritis was also observed at 750 and 1,500 ppm (NTP TR108 (1978)). (2) There is a report that in a 60-week study with rats dosed by drinking water, in the 500 mg/L dose group (500 ppm, converted value: 62.5 mg/kg/day, within the range of Category 2), hyperplasia of the urinary bladder mucosa in 9 animals and hyperplasia of the liver in 8 animals was observed among 13 surviving animals (IARC 29 (1982)). [Reference Data, etc.] (3) There is a report that in a 13-week study with mice dosed by feeding, hemosiderin pigmentation in the spleen at 1,500 ppm (converted value: 225 mg/kg/day, exceeding the range of Category 2), diffuse hepatocellular degeneration at 3,000 ppm, hemosiderin pigmentation in the kidney, pigmentation of the liver and thyroid, and altered hepatocellular foci at 6,000 ppm, and basophilic altered hepatocellular foci, hyperplasia of the bile duct of the liver at 12,500 ppm were observed (NTP TR108 (1978)).
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 (Acute)	Not classified	- -	-	-	It was classified as "Not classified" from 96-hour LC50 > 180 mg/L for fish (Pimephales promelas) (EPA AQUIRE: 2018, Little, L.W. et al. (1974)).
11	Hazardous to the aquatic environment (Long-term)	Not classified	- -	-	-	Chronic toxicity data were not obtained. It was classified as "Not classified" because no bioaccumulation is estimated (LogKow: 4.9 (EST, PHYSPROP Database: 2018)), and it was classified as "Not classified" in acute toxicity although it is not rapidly degradable (not readily degradable, an average degradation rate by BOD: -1% (J-CHECK, 2001)).
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	No data available.

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.

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