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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	1071-93-8
Chemical Name	Hexanedioic acid, 1,6-dihydrazide
Substance ID	R02-A-019-METI, MOE
Classification year (FY)	FY2020
Ministry who conducted the classification	Ministry of Economy, Trade and Industry (METI)/Ministry of the Environment (MOE)
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	Classification not possible	- -	-	-	There is a chemical group associated with explosive properties (hydrazines) present in the molecule, but the classification is not possible due to no data.
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. Besides, there is information that it is combustible (GESTIS (accessed 2020)).
8	Self-reactive substances and mixtures	Classification not possible	- -	-	-	There is a chemical group associated with explosive properties (hydrazines) present in the molecule, but the classification is not possible due to no data.
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	- -	-	-	Classification is not possible because test methods applicable to solid substances are not available.
17	Desensitized explosives	Classification not possible	- -	-	-	There is a chemical group associated with explosive properties (hydrazines) present in the molecule, but the classification is not possible due to no data.

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 (females): > 2,000 mg/kg (OECD TG 423) (REACH registration dossier (Accessed Aug. 2020))
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)	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1). [Evidence Data] (1) LC50 for rats (4 hours): > 5.3 mg/L (REACH registration dossier (Accessed Aug. 2020))
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1). [Evidence Data] (1) It is reported that in a skin irritation test with rabbits (n = 3) (OECD TG 404, GLP, semi-occlusive, 4-hour application, 72-hour observation), no skin irritation was seen (erythema/eschar score: 0/0/0, edema score: 0/0/0) (REACH registration dossier (Accessed Aug. 2020)).
3	Serious eye damage/eye irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1). [Evidence Data] (1) It is reported that in an eye irritation test with rabbits (n = 3) (OECD TG 405, GLP, 72-hour observation), no eye irritation was seen (corneal opacity score: 0/0/0, iritis score: 0/0/0, conjunctival redness score: 0/0/0, chemosis score: 0/0/0) (REACH registration dossier (Accessed Aug. 2020)).
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Category 1B	Warning	H317	P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501	[Rationale for the Classification] It was classified in Category 1B from (1), (2). As for mouse tests, knowledge contradicting to (1) was observed in (3), (4), but by considering the results of a test in guinea pigs (2), it was classified in Category 1B. [Evidence Data] (1) It is reported that in a local lymph node assay (LLNA) with mice (n = 4/group) (OECD TG 429, GLP), stimulation index (SI values) was 4.2 (5%), 9.1 (10%), 9.9 (25%) (REACH registration dossier (Accessed Aug. 2020)). (2) It is reported that in a maximization test with guinea pigs (n = 10/group) (OECD TG 406, intradermal administration: a 25% or 50% solution), a positive rate was all 100% (10/10) after 24, 48, 72 hours in both group administered a 25% and 50% solution (REACH registration dossier (Accessed Aug. 2020)). [Reference Data, etc.] (3) It is reported that in a local lymph node assay (LLNA) with mice (n = 5/group) (OECD TG 429, GLP), stimulation index (SI values) was 0.9 (0.25%), 1.0 (0.5%), 1.6 (1.6%) (REACH registration dossier (Accessed Aug. 2020)). (4) It is reported that in a local lymph node assay (LLNA) with mice (n = 5/group) (OECD TG 429, GLP), stimulation index (SI values) was 1.24 (2.5%), 1.48 (5%), 1.20 (10%) (REACH registration dossier (Accessed Aug. 2020)).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (6), it was classified as "Not classified." [Evidence Data] (1) In a micronucleus test using mice (OECD TG 474), negative results (oral administration and intraperitoneal administration) were reported (EFSA (2015)). (2) In a bacterial reverse mutation test (OECD TG 471), negative results were reported (JECDB (Accessed on May 2020), EFSA (2015), REACH registration dossier (Accessed on May 2020)). (3) In a chromosomal aberration test using the human lymphocytes (OECD TG 473), negative results were reported (REACH registration dossier (Accessed on May 2020)). (4) In an in vitro mammalian cell chromosome aberration test (OECD TG 473), negative results were reported (JECDB (Accessed on May 2020)). (5) In an in vitro mammalian cell gene mutation test (OECD TG 476), negative results were reported (REACH registration dossier (Accessed on May 2020)). (6) In a mouse lymphoma assay, negative results were reported (EFSA (2015)).
6	Carcinogenicity	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
7	Reproductive toxicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) It was reported that in a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test with rats dosed by gavage (OECD TG422, for 42 days including two weeks prior to mating (males), for 42 to 58 days including two weeks prior to mating and until day 4 of lactation (females)), at 300 mg/kg/day, emaciation, urinary incontinence, diarrhea (one case of infertility), lower hemoglobin/MCHC levels, and a tendency of an increase in the number of dams whose one or more newborns died during the lactation period were observed in parental animals, while no significant changes in the number of live pups and viability index on day 4 were observed in pups (Safety Study Report (Ministry of Economy, Trade and Industry (METI), 2011)). (2) It was reported that in a developmental toxicity study with rats dosed by gavage (OECD TG414, gestation days 6 to 20), at 300 mg/kg/day, 1/22 females died and reduced body weight gain and reduced food consumption were observed in parental animals, while only lower body weights were observed in pups (REACH registration dossier (Accessed Aug. 2020)).
8	Specific target organ toxicity - Single exposure	Classification not possible	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified" in the oral route and inhalation route. However, there was not sufficient information available for classification in the dermal route. Therefore, classification was not possible due to lack of data. [Evidence Data] (1) It was reported that in an acute oral toxicity test with rats dosed by gavage (OECD TG423, GLP), no effects were observed at 2,000 mg/kg (upper limit of Category 2) (REACH registration dossier (Accessed Aug. 2020)). (2) It was reported that in a (dust) inhalation exposure test with rats (for 4 hours), no effects were observed at 5.3 mg/L (in the range corresponding to "Not classified") (REACH registration dossier (Accessed Aug. 2020)).
9	Specific target organ toxicity - Repeated exposure	Classification not possible	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified" in the oral route. However, there was not sufficient information available for classification in the other routes. Therefore, classification was not possible due to lack of data. [Evidence Data] (1) It was reported that in a repeated dose 90-day oral toxicity study with rats dosed by gavage (OECD TG408, GLP), no effects were observed at 100 mg/kg/day (upper limit of Category 2), but liver effects (increased weight, single cell necrosis, increased ALT, AST, ALP levels) were observed at and above 300 mg/kg/day (in the range corresponding to "Not classified") and hematological effects (decreased hemoglobin/hematocrit levels, increased ratio of RDW, reduced MCV/MCH (females), reduced red blood cell counts (males)), liver effects (higher total bilirubin levels), effects on the brain and sciatic nerve, a decrease in body weight and a slight reduction in food consumption (males) were observed at 1,000 mg/kg/day (in the range corresponding to "Not classified") (REACH registration dossier (Accessed Aug. 2020)). (2) It was reported that in a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test with rats dosed by gavage (OECD TG422, GLP), emaciation, incontinence of urine, diarrhea/loose stool (one male of the recovery test group and one female of the treated group) and decreased hemoglobin and MCHC (females) were observed at 300 mg/kg/day (converted guidance value: 140 mg/kg/day, in the range corresponding to "Not classified") (Safety Study Report (Ministry of Economy, Trade and Industry (METI), 2011)).
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)	Category 2	- -	H401	P273 P501	It was classified in Category 2 from 72-hour EC50 = 8.7 mg/L for algae (Raphidocelis subcapitata) (REACH registration dossier, 2021).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 2	-	H411	P273 P391 P501	If chronic toxicity data are used, then it is classified in Category 2 because it was not rapidly degradable (not readily degradable, a 28-day degradation rate by BOD: 1% (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, METI, 2001)) and due to 72-hour NOErC = 0.22 mg/L for algae (Raphidocelis subcapitata) (REACH registration dossier, 2021). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained, then it is classified as "Not classified" because it was not rapidly degradable (not readily degradable, a degradation rate by BOD: 1% (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, METI, 2001)) and due to 96-hour LC50 > 100 mg/L for fish (Cyprinus carpio) (REACH registration dossier, 2021). By drawing a comparison between the above results, it was classified in Category 2.
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	This substance is not listed in the Annexes to the Montreal Protocol.

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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